Настройки

Укажите год
-

Небесная энциклопедия

Космические корабли и станции, автоматические КА и методы их проектирования, бортовые комплексы управления, системы и средства жизнеобеспечения, особенности технологии производства ракетно-космических систем

Подробнее
-

Мониторинг СМИ

Мониторинг СМИ и социальных сетей. Сканирование интернета, новостных сайтов, специализированных контентных площадок на базе мессенджеров. Гибкие настройки фильтров и первоначальных источников.

Подробнее

Форма поиска

Поддерживает ввод нескольких поисковых фраз (по одной на строку). При поиске обеспечивает поддержку морфологии русского и английского языка
Ведите корректный номера.
Ведите корректный номера.
Ведите корректный номера.
Ведите корректный номера.
Укажите год
Укажите год
Применить Всего найдено 3684. Отображено 100.
19-07-2012 дата публикации

Modulators of cell cycle checkpoints and their use in combination with checkpoint kinase inhibitors

Номер: US20120184505A1
Автор: Janeta Popovici-Muller, Kristin E. Rosner, Timothy J. Guzi
Принадлежит: Individual

In its many embodiments, the present invention provides a novel class of pyrimidine analogs as targeted mechanism-based modulators of cell cycle checkpoints. Cancers and/or malignancies can be treated by administration of a cell cycle checkpoint modulator of the invention. Also discussed are suitable combinations of the cell cycle checkpoint modulator with a checkpoint kinase inhibitor to produce synergistic apoptosis in cancer cells. The invention also includes methods of treating cancers by administering the combination of the cell cycle checkpoint modulator and the checkpoint kinase inhibitor, pharmaceutical compositions comprising the cell cycle checkpoint modulator as well as combinations and pharmaceutical kits. An example cell cycle checkpoint modulator is shown below: formula (I).

Подробнее
Номер записи: 1
13-09-2012 дата публикации

Organic compound and photovoltaic device comprising the same

Номер: US20120227802A1
Автор: Alexey Nokel, Pavel Ivan Lazarev, Pavel Khokhlov
Принадлежит: Cryscade Solar Ltd

The present invention provides a organic compound of the general structural formula 1 and photovoltaic device and photovoltaic layer comprising thereof Said organic compound forms rod-like supramolecules and absorbs electromagnetic radiation in at least one predetermined spectral subrange within a wavelength range from 400 to 3000 nm with excitation of electron-hole pairs. The polycyclic core Cor 1 , the bridging group B, and the polycyclic core Cor 2 form a molecular system selected from the list comprising donor-bridge-acceptor-bridge-donor and acceptor-bridge-donor-bridge-acceptor in which a dissociation of excited electron-hole pairs is carried out. A solution of the organic compound or its salt forms a solid photovoltaic layer on a substrate.

Подробнее
Номер записи: 2
17-01-2013 дата публикации

New Chemical Entities To Be Used For Wee1 Inhibition For The Treatment Of Cancer

Номер: US20130018045A1
Автор: Chunqui Lai, Julie M. Miyashiro, Keith W. Woods, Thomas D. Penning
Принадлежит: ABBOTT LABORATORIES

The present invention relates to compounds of formula (I) or pharmaceutical acceptable salts, wherein R 1 , R 2 , R 3 , A, B, and n are defined in the description. The present invention relates also to compositions containing said compounds which are useful for inhibiting kinases such as wee-1 and methods of treating diseases such as cancer.

Подробнее
Номер записи: 3
21-03-2013 дата публикации

Spirooxazine radical derivatives and reversible isomerization reaction

Номер: US20130072678A1
Автор: Atsumasa Sawada
Принадлежит: NEC Corp

The present invention can provide new spirooxazine radical derivatives of the following general formula (1) which have chromic property enabling the distinction between the radical species and the cation species on the basis of absorption wavelength:

Подробнее
Номер записи: 4
28-03-2013 дата публикации

GYRASE INHIBITORS

Номер: US20130079323A1
Автор: Bensen Daniel, Chen Zhiyong, Creighton Christopher J., Finn John, Hilgers Mark, Lam Thanh To, Li Xiaoming, Tari Leslie William, Trzoss Michael, Zhang Junhu
Принадлежит: TRIUS THERAPEUTICS, INC.

Novel gyrase inhibitors and related compositions and methods are useful for impeding bacterial growth. Compounds of Formula (I), are disclosed: Formula (I), wherein Y is N or CH; Z is N or CR; Ris H, a substituted or unsubstituted hydrocarbyl residue (1-3C) containing 0-2 heteroatoms selected from O, S and N, or is an inorganic residue; L is O, S, NR, or CRR; Ris H or Calkyl; Rand Rare each independently H or Calkyl; Ris H, a hydrocarbyl residue (1-40C) containing 0-10 heteroatoms selected from O, S and N optionally substituted with an inorganic residue; Ris H, an inorganic residue, or a hydrocarbyl residue (1-30C) containing 0-12 heteroatoms selected from O, S and N and containing 0-10 inorganic residues, wherein Rand Rtogether may join to form a fused ring; and Ris selected from the group consisting of H, Calkyl, Calkenyl, Calkynyl, halo Calkyl, halo Calkenyl, halo Calkynyl, Chydroxyalkyl, Calkyl chloride, Calkenyl chloride, and Calkynyl chloride; or a pharmaceutically-acceptable salt, ester, or prodrug thereof. 2. The compound of claim 1 , whereinY is N; and{'sub': '2', 'L is O, S, NH, or CH.'}3. The compound of claim 1 , wherein Z is CR claim 1 , wherein Ris selected from the group consisting of hydrogen claim 1 , halo claim 1 , unsubstituted Calkyl claim 1 , and Calkyl substituted with one or more substituents selected from the group consisting of ═O claim 1 , halo claim 1 , NH claim 1 , NHCH claim 1 , ≡N claim 1 , and Calkenyl claim 1 , wherein Rand Rtogether may join to form a fused ring.4. The compound of claim 1 , wherein Ris methyl claim 1 , C(O)CH claim 1 , C(O)NH claim 1 , CHOH claim 1 , CF claim 1 , CN claim 1 , CHF claim 1 , CHO claim 1 , acetyl claim 1 , Cl or Br.5. The compound of claim 1 , wherein Rcomprises at least one aryl or heteroaryl moiety.6. The compound of claim 1 , wherein the at least one aryl or a heteraryl moiety of Ris directly linked to L.7. The compound of claim 1 , wherein the at least one aryl or heteraryl moiety of Ris substituted ...

Подробнее
Номер записи: 5
04-04-2013 дата публикации

AMINOACID DERIVATIVES, THEIR PROCESS OF PREPARATION AND THEIR THERAPEUTICAL USES AS INHIBITORS OF ONCOGENIC SIGNALS BY THE MET FAMILY

Номер: US20130085143A1
Автор: BOSCH Joan, COLOMBO Francesco, DONO Rosanna, LEROUX Vincent, MAIGRET Bernard, MAINA Flavio, PASSARELLA Daniele, PICCOLO Oreste
Принадлежит:

Novel amino acids derivatives, in particular some amino acid amides derivatives, their process of preparation and their use for inhibiting Met-triggered disorders, in particular cancer. 2. The compounds according to in which m=0 or 1 claim 1 , p=0 claim 1 , r=0 and T=H.4. The compounds according to claim 1 , in which W═W═H.5. The compounds according to claim 1 , in which n=0 or 1 and X is H or an optionally substituted aryl or heteroaryl.6. The compounds according to claim 1 , in which X is phenyl.7. The compounds according to claim 1 , in which Y is an -alkylaryl claim 1 , such as —CHaryl claim 1 , where the aryl is optionally substituted by one or more identical or different substituents chosen from halogen claim 1 , OR claim 1 , NRR′ claim 1 , SR claim 1 , alkyl claim 1 , CN claim 1 , perhalogenoalkyl.13. The process according to claim 10 , further comprising the step of isolating the obtained compound.14. A pharmaceutical composition comprising a compound of formula (I) as defined in and a pharmaceutically acceptable carrier.15. The composition according to where said carrier is a cyclodextrin.16. A compound of formula (I) as defined in for inhibiting the Met family.17. A compound of formula (I) as defined in for treating and/or preventing Met family-triggered disorders.18. A compound of formula (I) according to for treating and/or preventing cancer(s) claim 17 , infections diseases and pain.19. A combination of a compound as defined in with one or more agent(s) and/or pharmaceutical composition(s) useful for the treatment and/or prevention of cancer(s) claim 1 , infections diseases and pain.20. A compound of formula (I) as defined in for treating and/or preventing distinct tumours characterised by alteration of selective signals. The present invention is related to novel aminoacids derivatives, pharmaceutical compositions comprising the same, processes for the preparation of said derivatives and uses of said compositions. Particularly, the present invention ...

Подробнее
Номер записи: 6
18-04-2013 дата публикации

DUAL-ACTING ANTIHYPERTENSIVE AGENTS

Номер: US20130096162A1
Автор: Allegretti Paul, Choi Seok-ki, Fatheree Paul R., Gendron Roland, Jendza Keith, McKinnell Robert Murray, McMurtrie Darren, Olson Brooke
Принадлежит:

The invention is directed to compounds having the formula: 2. The compound of claim 1 , wherein r is 1.3. (canceled)5. The compound of claim 4 , wherein Ris selected from —COOH claim 4 , —SONHR claim 4 , and tetrazol-5-yl.711-. (canceled)12. The compound of claim 1 , wherein Ris selected from —Calkyl and —Calkylene-O—Calkylene-R claim 1 , where Ris —Calkyl.13. The compound of claim 12 , wherein Ris selected from —Calkyl and —O—Calkyl.14. The compound of claim 1 , wherein X is —Calkylene- claim 1 , 1 to 4-CH-moieties in the alkylene are replaced with a —NR—C(O)— or —C(O)—NR— moiety claim 1 , and Ris selected from H and —OH.15. The compound of wherein X is selected from: —C(O)NH—; —CH—NHC(O)—; —C(O)NH—CH—; —C(O)NH—NHC(O)—; —CH═C(—CH-2-thiophene)-C(O)NH—; —(CH)—NHC(O)—; —C(O)NH—CH—CH(COOH)—CH—; —C(O)NH—CH(benzyl)-CH—NHC(O)—; —C(O)NH—CH(benzyl)-CH—C(O)NH—; —CH—NHC(O)—CH—NHC(O)—; —CH—NHC(O)-cyclohexylene-NHC(O)—; —CH—N(OH)C(O)-cyclohexylene-NHC(O)—; —CH—NHC(O)—CH—CH(COOH)—NHC(O)—; —CH—NHC(O)—(CH)—NHC(O)—; —C(O)NH—(CH)—C(O)N(OH)—CH—; —C(O)NH—(CH)—CH(COOH)—NHC(O)—; —C(O)NH—(CH)—NHC(O)—; —CH—NHC(O)—(CH)—CH(COOH)—NHC(O)—; —C(O)NH—(CH)—CH(COOH)—NHC(O)—; —C(O)NH—(CH)—NHC(O)—CH—NHC(O)—; —C(O)NH—(CH)—NHC(O)-cyclohexylene-NHC(O)—; —CH—NHC(O)—(CH)—NHC(O)—; —C(O)NH—(CH)—CH(COOH)—NHC(O)—; —CH—NHC(O)—(CH)—NHC(O)-cyclohexylene-NHC(O)—; —CH—C(O)NH—(CH)—NHC(O)-cyclohexylene-NHC(O)—; —C(O)NH—(CH)—NHC(O)—CH—NHC(O)—; —C(O)NH—(CH)—NHC(O)-cyclohexylene-NHC(O)—; —CH—NHC(O)—(CH)—NHC(O)—; —CH—NHC(O)—(CH)—NHC(O)-cyclohexylene-NHC(O)—; —C(O)NH—(CH)—NHC(O)-cyclohexylene-NHC(O)—; and —CH—NHC(O)—(CH)—NHC(O)-cyclohexylene-NHC(O)—.16. The compound of claim 15 , wherein X is selected from —C(O)NH— and —CH—NHC(O)—.17. The compound of claim 1 , wherein Ris selected from —Calkylene-SR claim 1 , —Calkylene-C(O)NRR claim 1 , —Calkylene-NR—C(O)R claim 1 , —NH—Calkylene-P(O)(OR) claim 1 , —Calkylene-P(O)ORR claim 1 , —Calkylene-CHR—COOH claim 1 , and —Calkylene-C(O)NR—CHR—COOH; Ris H claim 1 , Ris —OH claim 1 ...

Подробнее
Номер записи: 7
02-05-2013 дата публикации

PROCESS FOR MAKING THIENOPYRIMIDINE COMPOUNDS

Номер: US20130109852A1
Автор: Babu Srinivasan, CHENG Zhigang, REYNOLDS Mark E., SAVAGE Scott J., Tian Qingping, Yajima Herbert
Принадлежит: Genentech, Inc.

The invention provides processes of preparing, separating, and purifying PI3K inhibitor, Formula I and II compounds, and novel intermediates for preparing Formula I and II compounds. 1. The compound selected from 14 and 14A This application is a divisional of U.S. Ser. No. 12/739,434 filed 29 Jul. 2010, which is a National Stage Application under 35 U.S.C. §371 and claims the benefit of priority to International Application No. PCT/US2008/081204 filed on 24 Oct. 2008, which claims the benefit under 35 USC §119(e) of U.S. Provisional Application Ser. No. 60/982,562 filed on 25 Oct. 2007, each of which are incorporated by reference in entirety.The invention relates generally to processes for making and purifying thienopyrimidine compounds with anti-cancer activity and more specifically to compounds which inhibit PI3 kinase activity.Phosphatidylinositol (hereinafter abbreviated as “PI”) is one of a number of phospholipids found in cell membranes. In recent years it has become clear that PI plays an important role in intracellular signal transduction. Cell signaling via 3′-phosphorylated phosphoinositides has been implicated in a variety of cellular processes, e.g., malignant transformation, growth factor signaling, inflammation, and immunity (Rameh et al (1999) J. Biol Chem, 274:8347-8350). The enzyme responsible for generating these phosphorylated signaling products, phosphatidylinositol 3-kinase (also referred to as PI 3-kinase or PI3K), was originally identified as an activity associated with viral oncoproteins and growth factor receptor tyrosine kinases that phosphorylate phosphatidylinositol (PI) and its phosphorylated derivatives at the 3′-hydroxyl of the inositol ring (Panayotou et al (1992) Trends Cell Biol 2:358-60).Phosphoinositide 3-kinases (PI3K) are lipid kinases that phosphorylate lipids at the 3-hydroxyl residue of an inositol ring (Whitman et al (1988) Nature, 332:664). The 3-phosphorylated phospholipids (PIP3s) generated by PI3-kinases act as second ...

Подробнее
Номер записи: 8
23-05-2013 дата публикации

COMPOUNDS FOR THE REDUCTION OF BETA-AMYLOID PRODUCTION

Номер: US20130131049A1
Автор: Wu Yong-Jin
Принадлежит:

Compounds of formula (I), including pharmaceutically acceptable salts thereof, are set forth herein: 2. The compound of claim 1 , wherein:{'sub': 1', '2', '3', '4', '5', '6', '1', '6', '1', '6, 'R, R, R, R, R, and Rare independently hydrogen, C-Calkyl or C-Ccycloalkyl;'}{'sub': 1-4', '1-4', '1-4', '1', '6', '1', '6', '2', '4, 'Y is phenyl or thiophenyl and Z is a pyridyl, pyrimidinyl or pyrazinyl, wherein each Y and Z group can be optionally substituted with from 0-3 substituents selected from hydrogen, halogen, amino, Calkylamino, Cdialkylamino, haloCalkyl, OH, CN, C-Calkyl or cycloalkyl, C-Calkoxy, or C-Calkynyl;'}L is either a bond or is —NHCO—; andm is 1 or 2.3. The compound of claim 2 , wherein:{'sub': 1', '2', '3', '4', '5', '6, 'R, R, R, R, R, and Rare hydrogen;'}{'sub': 2', '4, 'Y is phenyl and Z is a pyridyl, wherein each Y and Z group can be optionally substituted with from 0-3 halogen substituents and Z can be optionally substituted with from 0-3 halogen, cyano, or C-Calkynyl substituents;'}L is either a bond or is —NHCO—; andm is 1 or 2.4. The compound of claim 2 , wherein:{'sub': 1', '2', '3', '4', '5', '6, 'R, R, R, R, R, and Rare hydrogen;'}{'sub': 2', '4, 'Y is phenyl optionally substituted with from 0-3 halogen, cyano, or C-Calkynyl substituents;'}L and Z together can be absent; andm is 1 or 2.5. A compound of any claims of 1 to 3 claim 2 , wherein the configuration of the chiral center adjacent to the nitrogen of the aminothiazine is (R) or a pharmaceutically acceptable salt thereof.6. The compound of claim 4 , which is selected from the group consisting of:N-(3-((4aR,7aR)-2-amino-4-a,5,6,7a-tetrahydro-4H-furo[2,3-d][1,3]thiazin-7a-yl)-4-fluorophenyl)-5-chloropicolinamide;N-(3-((4aR,7aR)-2-amino-4-a,5,6,7a-tetrahydro-4H-furo[2,3-d][1,3]thiazin-7a-yl)-4-cyanophenyl)-5-chloropicolinamide;N-(3-((4aR,7aR)-2-amino-4-a,5,6,7a-tetrahydro-4H-furo[2,3-d][1,3]thiazin-7a-yl)-4-cyanophenyl)-5-bromopicolinamide;N-(3-((4aR,7aR)-2-amino-4a,5,6,7a-tetrahydro-4H- ...

Подробнее
Номер записи: 9
23-05-2013 дата публикации

FUSED HETEROCYCLIC COMPOUND AND APPLICATION THEREOF

Номер: US20130131050A1
Автор: Asano Kouhei, MATSUNAGA Nobuyuki, OKAMOTO Rei, Suzuki Hideo, Tokuhara Hidekazu, YAMAMOTO Takeshi
Принадлежит: Takeda Pharmaceutical Company Limited

The present invention provides a compound useful for the prophylaxis or treatment of eicosanoid-associated diseases such as atherosclerosis, atherothrombosis, diabetes, obesity, asthma, fever, pain, cancer, rheumatism, osteoarthritis, atopic dermatitis and the like, and having superior pharmacological action, physicochemical properties and the like. 2. The compound or salt of claim 1 , wherein{'sup': '2', 'Xis 0; and'}{'sup': '4', 'sub': '1-6', 'Ris a Calkyl group optionally substituted by 1 to 3 halogen atoms.'}6. 2-(2 claim 1 ,2 claim 1 ,2-Trifluoroethoxy)-3-[4-(2 claim 1 ,2 claim 1 ,2-trifluoroethoxy)phenyl]-5 claim 1 ,6-dihydropyrido[2 claim 1 ,3-d]pyrimidine-4 claim 1 ,7(3H claim 1 ,8H)-dione or a salt thereof.7. 2-Ethoxy-3-[4-(2 claim 1 ,2 claim 1 ,2-trifluoroethoxy)phenyl]-5 claim 1 ,6-dihydropyrido[2 claim 1 ,3-d]pyrimidine-4 claim 1 ,7(3H claim 1 ,8H)-dione or a salt thereof.8. 3-[4-(2 claim 1 ,2 claim 1 ,2-Trifluoroethoxy)phenyl]-2-(3 claim 1 ,3 claim 1 ,3-trifluoropropyl)-5 claim 1 ,6-dihydropyrido[2 claim 1 ,3-d]pyrimidine-4 claim 1 ,7(3H claim 1 ,8H)-dione or a salt thereof.9. A medicament comprising the compound or salt of .10. The medicament of claim 9 , which is a delta-5-desaturase inhibitor.11. The medicament of claim 9 , which is an agent for the prophylaxis or treatment of eicosanoid-associated diseases.12. The medicament of claim 9 , which is an agent for the prophylaxis or treatment of arteriosclerosis.13. The medicament of claim 9 , which is an agent for the prophylaxis or treatment of diabetes or obesity.14. A method for the prophylaxis or treatment of arteriosclerosis in a mammal claim 1 , comprising administering an effective amount of the compound or salt of to the mammal.15. A method for the prophylaxis or treatment of diabetes or obesity in a mammal claim 1 , comprising administering an effective amount of the compound or salt of to the mammal.1617-. (canceled)18. The compound or salt of for use in the prophylaxis or treatment of ...

Подробнее
Номер записи: 10
13-06-2013 дата публикации

Novel Sultam Compounds

Номер: US20130150376A1
Автор: "ONeill Brian Thomas", Brodney Michael Aaron, Efremov Ivan Viktorovich, Helal Christopher John
Принадлежит: PFIZER INC.

Compounds and pharmaceutically acceptable salts of the compounds are disclosed, wherein the compounds have the structure of Formula I (I) as defined in the specification. Corresponding pharmaceutical compositions, methods of treatment, methods of synthesis, and intermediates are also disclosed. 2. A compound of wherein A is Ccycloalkyl claim 1 , Caryl claim 1 , 4- to 10-membered heterocycloalkyl claim 1 , or 5- to 10-membered heteroaryl and A is optionally substituted with one to three Rsubstituents selected from the group consisting of Calkyl claim 1 , halogen claim 1 , cyano claim 1 , —COR claim 1 , —CON(R) claim 1 , —N(R)COR claim 1 , —N(R)COR claim 1 , —N(R)CON(R) claim 1 , —N(R)SOR claim 1 , —SOR claim 1 , —SON(R) claim 1 , —(C(R))—Ccycloalkyl claim 1 , —(C(R))-(4- to 10-membered heterocycloalkyl) claim 1 , —(C(R))—Caryl claim 1 , —(C(R))-(5- to 10-membered heteroaryl) claim 1 , —(C(R))—N(R) claim 1 , or —(C(R))—OR; wherein each Ralkyl claim 1 , cycloalkyl claim 1 , heterocycloalkyl claim 1 , aryl claim 1 , or heteroaryl is optionally substituted by one to three cyano claim 1 , Calkyl claim 1 , Ccycloalkyl claim 1 , halogen claim 1 , —CFor —OR; and pharmaceutically acceptable salts thereof.3. A compound of wherein A is Caryl and A is optionally substituted with one to three Rsubstituents selected from the group consisting of Calkyl claim 2 , halogen claim 2 , cyano claim 2 , —COR claim 2 , —CON(R) claim 2 , —(C(R))Ccycloalkyl claim 2 , —(C(R))-(4- to 10-membered heterocycloalkyl) claim 2 , —(C(R))—Caryl claim 2 , —(C(R))-(5- to 10-membered heteroaryl) claim 2 , or —(C(R))—OR; wherein each Ralkyl claim 2 , cycloalkyl claim 2 , heterocycloalkyl claim 2 , aryl claim 2 , or heteroaryl is optionally substituted by one to three cyano claim 2 , Calkyl claim 2 , Ccycloalkyl claim 2 , halogen claim 2 , —CFor —OR; and pharmaceutically acceptable salts thereof.4. A compound of wherein t is 0 or 1; B is —(C(R))—Caryl claim 3 , or —(C(R))-(5- to 10-membered heteroaryl); ...

Подробнее
Номер записи: 11
18-07-2013 дата публикации

HETEROCYCLIC COMPOUND AND USE THEREOF

Номер: US20130184266A1
Автор: ASANO Yasutomi, Honda Eiji, IMAEDA Toshihiro, KORI Masakuni, Mochizuki Michiyo, Nakamura Shinji, TOYOFUKU Masashi, Ujikawa Osamu
Принадлежит: Takeda Pharmaceutical Company Limited

Provided is a compound represented by the formula (I): 123-. (canceled)24. 9-[4-(Cyclohexyloxy)phenyl]-7-methyl-3 ,4-dihydropyrazino[2 ,1-c][1 ,2 ,4]thiadiazine 2 ,2-dioxide or a pharmaceutically acceptable salt thereof.25. A medicament comprising 9-[4-(cyclohexyloxy)phenyl]-7-methyl-3 ,4-dihydropyrazino[2 ,1-c][1 ,2 ,4]thiadiazine 2 ,2-dioxide or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier. The present invention relates to a heterocyclic compound, particularly a heterocyclic compound having an AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) receptor potentiating action.Glutamate is the most abundant excitatory neurotransmitter in the mammalian central nervous system. Glutamate plays a pivotal role in cognition, mood, and motor function, and its neurotransmission becomes unstable in psychiatric diseases and neurological disorder. Glutamate receptors are divided into ligand gated ion channels and G protein-coupled receptors, and the ligand gated ion channels are further divided into α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors, N-methyl-D-aspartic acid (NMDA) receptors, and kainic acid (KA) receptors. (non-patent document 1)AMPA receptor is one kind of receptor for excitatory neurotransmitter glutamate, and was named for the selective activation of the receptor by AMPA. AMPA receptors are composed of 4 subunits (GluR1, GluR2, GluR3, GluR4). Each subunit exists in flip and flop alternatively spliced variants. AMPA receptors form homo- or hetero-tetramers composed of these subunits in vivo. The physiological property of AMPA receptor has been reported to change depending on the subunit composition. (non-patent documents 1, 2, 3)The importance of AMPA receptor in cerebrophysiology is well known, and a compound having an AMPA receptor potentiating action is expected to be useful as a prophylactic or therapeutic drug for psychiatric diseases, neurodegenerative diseases, cognitive disorders, ...

Подробнее
Номер записи: 12
25-07-2013 дата публикации

HETEROCYCLIC COMPOUND AND USE THEREOF

Номер: US20130190291A1
Автор: ASANO Yasutomi, Honda Eiji, IMAEDA Toshihiro, KORI Masakuni, Mochizuki Michiyo, Nakamura Shinji, TOYOFUKU Masashi, Ujikawa Osamu
Принадлежит: Takeda Pharmaceutical Company Limited

Provided is a compound represented by the formula (I): 5. The compound according to claim 2 , wherein L is a bond claim 2 , or a salt thereof.6. The compound according to claim 2 , wherein ring D is an optionally substituted 3-8-membered monocyclic non-aromatic hydrocarbon ring claim 2 , an optionally substituted 6-14-membered aromatic hydrocarbon ring claim 2 , an optionally substituted 6-14-membered non-aromatic hydrocarbon ring claim 2 , an optionally substituted 5-6-membered monocyclic aromatic heterocycle claim 2 , an optionally substituted 3-8-membered monocyclic non-aromatic heterocycle claim 2 , an optionally substituted 8-14-membered condensed aromatic heterocycle or an optionally substituted 6-14-membered condensed non-aromatic heterocycle claim 2 , or a salt thereof.7. The compound according to claim 2 , wherein ring D is{'sub': '3-7', 'optionally substituted Ccycloalkane,'}{'sub': '6-14', 'optionally substituted Carene,'}optionally substituted dihydronaphthalene,optionally substituted tetrahydronaphthalene,optionally substituted dihydroinden,optionally substituted thiophene,optionally substituted azetidine,optionally substituted piperidine,optionally substituted furan,optionally substituted pyridine,optionally substituted pyrazole,optionally substituted 1,2,4-oxadiazole,optionally substituted dihydrobenzodioxin,optionally substituted dihydrobenzofuran,optionally substituted benzodioxole,optionally substituted benzofuran,optionally substituted indole,optionally substituted quinoline,optionally substituted benzimidazole,optionally substituted benzothiazole,optionally substituted indazole, oroptionally substituted dibenzothiophene,or a salt thereof.8. The compound according to claim 2 , wherein ring D is Ccycloalkane claim 2 , Carene claim 2 , dihydronaphthalene claim 2 , tetrahydronaphthalene claim 2 , dihydroinden claim 2 , thiophene claim 2 , azetidine claim 2 , piperidine claim 2 , furan claim 2 , pyridine claim 2 , pyrazole claim 2 , 1 claim 2 ,2 claim ...

Подробнее
Номер записи: 13
08-08-2013 дата публикации

FUSED HETEROCYCLIC DERIVATIVES AS S1P MODULATORS

Номер: US20130203737A1
Автор: Coolen Hein K.A.C., den Hartog Jacobus A.J., Iwema Bakker Wouter I., Sliedregt Leonardus A.J.M., Smid Pieter, van Dongen Maria J.P.
Принадлежит: AbbVie B.V.

The present invention relates to a fused heterocyclic derivative of the formula (I) 2. The compound of claim 1 , wherein 'a group selected from a (3-6C)cycloalkyl group and a (8-10C)bicyclic group wherein the group is optionally substituted with a halogen atom, (1-4C)alkyl, and a phenyl group wherein the phenyl group is optionally substituted with at least one substituent independently selected from a halogen atom, cyano, (1-4C)alkyl, (1-4C)alkoxy, a trifluoromethyl, and a trifluoromethoxy;', 'R1 is selected from'}{'sub': '2', 'W is selected from a bond, —O—, —CO—, —S—, —SO—, —SO—, —NH—, —CH═CH—, —C≡C—, and a trans-cyclopropylene;'}n is an integer from 0 to 4; andR2 is selected from H and at least one substituent independently selected from a halogen atom, (1-4C)alkyl optionally substituted with at least one fluoro and (1-4C)alkoxy optionally substituted with at least one fluoro atom.5. The compound of claim 1 , wherein Y is O.6. The compound of claim 1 , wherein R4 is selected from —(CH)—COOH claim 1 , —(CH)—COOH claim 1 , —CH—CHCH—COOH claim 1 , —CH—C(CH)—COOH claim 1 , —CHCH—CH—COOH claim 1 , —CH—CF—COOH claim 1 , and 1 claim 1 ,3-cyclobutylene-COOH.7. The compound of claim 1 , wherein R1 is a phenyl group optionally substituted with at least one substituent independently selected from halogen claim 1 , cyano claim 1 , (1-4C)alkyl optionally substituted with at least one halogen atom claim 1 , (1-4C)alkoxy optionally substituted with at least one halogen atom claim 1 , amino claim 1 , dimethylamino claim 1 , and (3-6C)cycloalkyl optionally substituted with a phenyl group wherein the phenyl group is optionally substituted with a substituent selected from (1-4C)alkyl and a halogen atom.8. The compound of claim 7 , wherein R1 is a phenyl group optionally substituted with at least one substituent independently selected from a halogen atom claim 7 , cyano claim 7 , (1-4C)alkyl claim 7 , (1-4C)alkoxy claim 7 , a trifluoromethyl claim 7 , and a trifluoromethoxy.9. The ...

Подробнее
Номер записи: 14
08-08-2013 дата публикации

FUSED AMINODIHYDROTHIAZINE DERIVATIVES

Номер: US20130203740A1
Автор: Farthing Christopher Neil, Hall Adrian
Принадлежит: Eisai R&D Management Co., Ltd.

The present invention relates to a fused aminodihydrothiazine derivative of formula (I): 15-. (canceled)6. A compound which is N-(3-((4aS ,5S ,7aS)-2-amino-5-(trifluoromethyl)-4-a ,5 ,7 ,7a-tetrahydro-4H-furo[3 ,4-d][1 ,3]thiazin-7a-yl)-4-fluorophenyl)-5-methoxypyrazine-2-carboxamide , or a pharmaceutically acceptable salt thereof.713-. (canceled)14. A pharmaceutical composition comprising the compound according to claim 6 , or a pharmaceutically acceptable salt thereof claim 6 , as an active ingredient in association with a pharmaceutically acceptable carrier.15. (canceled)16. A method of treating Down's syndrome claim 6 , comprising administering to a human subject suffering from Down's syndrome an effective amount of the compound according to claim 6 , or a pharmaceutically acceptable salt thereof.17. A method of treating Alzheimer-type dementia claim 6 , comprising administering to a human subject suffering from Alzheimer-type dementia an effective amount of the compound according to claim 6 , or a pharmaceutically acceptable salt thereof. The present invention relates to a fused aminodihydrothiazine derivative and pharmaceutical use thereof. More particularly, the present invention relates to a fused aminodihydrothiazine derivative which has an amyloid-β (hereinafter referred to as Aβ) protein production inhibitory effect or a beta-site amyloid-β precursor protein cleavage enzyme 1 (hereinafter referred to as BACE1 or beta-secretase) inhibitory effect and is effective for treating a neurodegenerative disease caused by Aβ protein, in particular, Alzheimer-type dementia, Down's syndrome or the like, and to a pharmaceutical composition comprising the fused aminodihydrothiazine derivative as an active ingredient.Alzheimer's disease is a disease characterized by degeneration and loss of neurons as well as formation of senile plaques and neurofibrillary tangles. Currently, only the symptoms of Alzheimer's disease are treated using a symptom-improving agent typified ...

Подробнее
Номер записи: 15
08-08-2013 дата публикации

PHARMACEUTICAL COMPOSITION COMPRISING A PYRIMIDINEONE DERIVATIVE

Номер: US20130203778A1
Автор: CHAUDHARI Sunil, Dhuppad Ulhas
Принадлежит: Glenmark Pharmaceuticals S.A.

The present patent application relates to a pharmaceutical composition comprising a fused pyrimidineone derivative having transient receptor potential modulating activity and a hydrophilic carrier. 1. A pharmaceutical composition comprising a solid dispersion that includes an active ingredient 7-{(E)-2-[2-(cyclopropylmethoxy)-3-methoxyphenyl]vinyl}-6-(4-trifluoromethoxy-phenyl)-5H-[1 ,3]thiazolo-[3 ,2-a]pyrimidin-5-one (“Compound I”) or its salt; and a hydrophilic carrier.2. (canceled)3. A pharmaceutical composition according to claim 1 , wherein the hydrophilic carrier includes surfactant claim 1 , complexing agent claim 1 , cosolvent claim 1 , polymer and mixtures thereof.4. A pharmaceutical composition according to claim 1 , wherein the hydrophilic carrier is a surfactant selected from poloxamer claim 1 , polyoxyethylene sorbitan ester claim 1 , polyoxyethylene sorbitan ester claim 1 , polyglyceryl-6-dioleate claim 1 , polyethylene glycol 15 hydroxy stearate claim 1 , diethylene glycol monoethyl ether claim 1 , propylene glycol dicaprylocaprate claim 1 , lecithin claim 1 , phospholipid claim 1 , lauroyl macrogolglycerides claim 1 , oleoyl macrogolglycerides claim 1 , and caprylocaproyl macrogolglycerides claim 1 , or mixtures thereof.5. A pharmaceutical composition according to claim 1 , wherein the hydrophilic carrier is a complexing agent selected from alpha-cyclodextrin claim 1 , beta-cyclodextrin claim 1 , gamma-cyclodextrin claim 1 , hydroxypropyl beta-cyclodextrin claim 1 , sulphobutyl ether beta cyclodextrin neutralized poly(acrylic acid) claim 1 , and crosslinked acrylic acid copolymers claim 1 , or mixtures thereof.6. A pharmaceutical composition according to claim 1 , wherein the hydrophilic carrier is a cosolvent selected from ethanol claim 1 , propanol claim 1 , isopropanol claim 1 , propylene glycol claim 1 , polyethylene glycol claim 1 , dichloromethane claim 1 , dimethylisosorbide claim 1 , ethyl lactate claim 1 , N-methylpyrrolidones claim 1 , ...

Подробнее
Номер записи: 16
15-08-2013 дата публикации

TRICYCLIC MGLUR5 RECEPTOR MODULATORS

Номер: US20130210804A1
Автор: Anthony Neville J., Gomez Robert P., LI Jing, Mercer Swati P., Roecker Anthony J., Stump Craig A., Williams Theresa M.
Принадлежит:

The present invention is directed to tricyclic compounds which are positive allosteric modulators of metabotropic glutamate receptors, particularly the mGluR5 receptor, and which are useful in the treatment or prevention of neurological and psychiatric disorders associated with glutamate dysfunction and diseases in which metabotropic glutamate receptors are involved. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which metabotropic glutamate receptors are involved. 5. The compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein A is selected from the group consisting of phenyl claim 1 , pyridyl and pyrrolyl.6. The compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Q is C and V is C.7. The compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Z is —CH—.8. The compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein R claim 1 , Rand Rare independently selected from the group consisting of:(1) hydrogen,(2) halogen,(3) hydroxyl,{'sub': '1-6', '(4) Calkyl, which is unsubstituted or substituted with halogen, hydroxyl, phenyl or napthyl,'}{'sub': '1-6', '(5) —O—Calkyl, which is unsubstituted or substituted with halogen, hydroxyl or phenyl,'}{'sub': 1-6', '1-6', '2, '(6) heteroaryl, wherein heteroaryl is selected from pyrrolyl, imidazolyl, indolyl, pyridyl, and pyrimidinyl, which is unsubstituted or substituted with halogen, hydroxyl, Calkyl, —O—Calkyl or —NO,'}{'sub': 1-6', '1-6', '2, '(7) phenyl, which is unsubstituted or substituted with halogen, hydroxyl, Calkyl, —O—Calkyl or —NO,'}{'sub': 1-6', '1-6', '2, '(8) —O-phenyl, which is unsubstituted or substituted with halogen, hydroxyl, Calkyl, —O—Calkyl or —NO, and'}{'sub': 1-6', '1-6', '1-6', '1-6', '1-6, '(9) —NH—Calkyl, or —N(Calkyl)(Calkyl), which is ...

Подробнее
Номер записи: 17
15-08-2013 дата публикации

TRICYCLIC INDOLE DERIVATIVES USEFUL ENDOTHELIAL LIPASE INHIBITORS

Номер: US20130210806A1
Автор: Connelly Margery A., Greco Michael, Ye Hong
Принадлежит: Janssen Pharmaceutica, NV

The present invention is directed to tricyclic indole derivatives, pharmaceutical compositions containing them and their use in the treatment of disorders and conditions modulated by endothelial lipase, for example, cardiovascular disorders. 13. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a compound of .14. A pharmaceutical composition made by mixing a compound of and a pharmaceutically acceptable carrier.15. A process for making a pharmaceutical composition comprising mixing a compound of and a pharmaceutically acceptable carrier.16. A method of treating a disorder mediated by the endothelial lipase claim 1 , comprising administering to a subject in need thereof a therapeutically effective amount of the compound of .17. The method of claim 16 , wherein the disorder mediated by the endothelial lipase is selected from the group consisting of atherosclerosis claim 16 , dyslipidemia claim 16 , low HDL and high LDL.18. A method of treating a disorder selected from the group consisting of atherosclerosis claim 13 , dyslipidemia claim 13 , low HDL and high LDL comprising administering to the subject in need thereof a therapeutically effective amount of the composition of .19. A method of treating a disorder selected from the group consisting of atherosclerosis claim 1 , dyslipidemia claim 1 , low HDL and high LDL comprising administering to the subject in need thereof a therapeutically effective amount of the compound of . The present application claims benefit of U.S. Provisional Patent Application Ser. No. 61/599,066, filed on Feb. 15, 2012, which is incorporated herein by reference in its entirety and for all purposes.The present invention is directed to tricyclic indole derivatives, pharmaceutical compositions containing them and their use in the treatment of disorders and conditions modulated by endothelial lipase. More particularly, the compounds of the present invention are endothelial lipase inhibitors, useful in the treatment ...

Подробнее
Номер записи: 18
15-08-2013 дата публикации

Tricyclic Compounds as Allosteric Modulators of Metabotropic Glutamate Receptors.

Номер: US20130210807A1
Автор: Boléa Christelle, Celanire Sylvain, Liverton Nigel J, Luo Yunfu
Принадлежит:

The present invention describes and claims compounds of the Structural Formula I, Structural Formula II, or Structural Formula III: wherein R, R, Rand R are —H or methyl, or Rand Rtaken together form a double bond, or R is —H and Rand Rtaken together form a spiro-cyclopropyl substituent, Ris —H or —F, and R5 is —H, methyl, —CI or —Br, Formula II wherein Ris —H, ethyl-, isopropyl-, cyclopropyl-, methyl- or methoxy-, Ris —H or —F, and “Y” is: (a) —CH—; (b) —CRH-0-CRR—, wherein R, R, and Rare independently —H or methyl; (c) —CRH—N(R)—CRR—, wherein R, R, and Rare independently —H or methyl; (d) —CH—C(R)(R)—C(R)(R)—, wherein R, R, Rand Rare independently —H or -methyl, or both Rand Rare —F, Rand Rare independently —H or -methyl, or both Rand Rare —F, or Rand Rtaken together are (0=), which together with the carbon to which they are attached forms a carbonyl group. 2) A pharmaceutical formulation comprising at least one compound of or a pharmaceutically acceptable salt thereof.3) Use of a compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , in the provision of a medicament for treating claim 1 , preventing claim 1 , or managing a disorder or disease which can be treated claim 1 , prevented claim 1 , or managed by administering an effective amount of an mGluR4 positive allosteric modulating compound.4) A medicament of formulated for use in the treatment or management of Parkinson's disease.5) A method of treating claim 3 , preventing claim 3 , or managing a disorder or disease which can be treated claim 3 , prevented claim 3 , or managed by administering an effective amount of an mGluR4 positive allosteric modulating compound comprising administering to a mammalian patient in need of such a medicament of in an effective amount in combination with an agent selected from the group consisting of: levodopa claim 3 , levodopa with a selective extracerebral decarboxylase inhibitor claim 3 , carbidopa claim 3 , entacapone claim 3 , a COMT inhibitor claim ...

Подробнее
Номер записи: 19
29-08-2013 дата публикации

FUSED TETRACYCLIC PYRIDO [4,3-B] INDOLE AND PYRIDO [3,4-B] INDOLE DERIVATIVES AND METHODS OF USE

Номер: US20130225558A1
Автор: CHAKRAVARTY Sarvajit, Hart Barry Patrick, JAIN Rajendra Parasmal
Принадлежит:

This disclosure is directed to fused tetracyclic pyrido[4,3-b>]indole and pyrido[3,4-b]indole derivatives. Pharmaceutical compositions comprising the compounds are also provided, as are methods of using the compounds in a variety of therapeutic applications, including the treatment of a cognitive disorder, psychotic disorder, neurotransmitter-mediated disorder and/or a neuronal disorder. 4. The compound of claim 3 , wherein Ris H or methyl.5. The compound of claim 3 , wherein each R claim 3 , R claim 3 , R claim 3 , R claim 3 , R claim 3 , R claim 3 , R claim 3 , R claim 3 , Rand R claim 3 , where applicable claim 3 , is independently H claim 3 , hydroxyl claim 3 , substituted or unsubstituted C-Calkyl claim 3 , substituted or unsubstituted aryl claim 3 , substituted or unsubstituted heteroaryl claim 3 , substituted or unsubstituted heterocyclyl claim 3 , substituted or unsubstituted aralkyl claim 3 , or acylamino claim 3 , or Rand Rare taken together with the carbon to which they are attached to form a carbonyl moiety claim 3 , or Rand a vicinal R claim 3 , where applicable claim 3 , are taken together to form a bond.6. The compound of claim 3 , wherein at least one of R claim 3 , R claim 3 , R claim 3 , R claim 3 , R claim 3 , R claim 3 , R claim 3 , R claim 3 , Rand Ris a group containing a cyclic moiety.7. The compound of claim 6 , wherein the group containing a cyclic moiety is selected from the group consisting of substituted or unsubstituted aryl claim 6 , substituted or unsubstituted heteroaryl claim 6 , substituted or unsubstituted cycloalkyl claim 6 , and substituted or unsubstituted heterocyclyl.8. The compound of claim 6 , wherein the group containing a cyclic moiety is a C-Calkyl claim 6 , or a C-Calkenyl claim 6 , substituted with a group selected from the group consisting of substituted or unsubstituted aryl claim 6 , substituted or unsubstituted heteroaryl claim 6 , substituted or unsubstituted cycloalkyl claim 6 , and substituted or unsubstituted ...

Подробнее
Номер записи: 20
29-08-2013 дата публикации

BICYCLIC HETEROCYCLIC SPIRO COMPOUNDS

Номер: US20130225624A1
Автор: BAR-NER Nira, FISHER Abraham, NACHUM Victoria
Принадлежит:

There are provided certain bicyclic heterocyclic compounds that act as M1 muscarinic receptor modulators. Compositions containing these compounds and their use are also disclosed. 2. A compound according to wherein R is methyl.3. A compound according to wherein p and n are each 1.58-. (canceled)9. A compound according to wherein Ris methyl.10. A compound according to wherein Ris H.11. A compound according to wherein Rand Rare each H.12. A compound according to wherein Ris H.13. A compound according to any wherein Y is S.14. A compound according to wherein Y is O.15. A compound according to wherein Ris optionally substituted —C(O)—(C)-indol-3-yl.16. A compound according to wherein Ris selected from the group consisting of —C(O)—CH-indol-3-yl claim 15 , —C(O)—CHCH-indol-3-yl claim 15 , —C(O)—CHCHCH-indol-3-yl claim 15 , trans —C(O)—CH═CH-indol-3-yl and —C(O)—CH(NH)—CH-indol-3-yl.1720-. (canceled)22. A compound according to wherein Ris selected from the group consisting of —SO-4-fluorophenyl claim 1 , —C(O)CH(n-propyl) claim 1 , —C(O)-(4-hydroxy-3 claim 1 ,5-di-tertbutylphenyl) and —C(O)—CHCH.2325-. (canceled)27. A compound according to which is selected from the group consisting of (1-(2 claim 1 ,8-dimethyl-1-thia-3 claim 1 ,8-diazaspiro[4.5]dec-3-yl)-3-(1H-indol-3-yl)propan-1-one) claim 1 , (+)-(1-(2 claim 1 ,8-dimethyl-1-thia-3 claim 1 ,8-diazaspiro[4.5]dec-3-yl)-3-(1H-indol-3-yl)propan-1-one) claim 1 , (−)-(1-(2 claim 1 ,8-dimethyl-1-thia-3 claim 1 ,8-diazaspiro[4.5]dec-3-yl)-3-(1H-indol-3-yl)propan-1-one) claim 1 , 1-(2 claim 1 ,8-dimethyl-1-oxa-3 claim 1 ,8-diazaspiro[4.5]dec-3-yl)-3-(1H-indol-3-yl)-propan-1-one claim 1 , (+)-1-(2 claim 1 ,8-dimethyl-1-oxa-3 claim 1 ,8-diazaspiro[4.5]dec-3-yl)-3-(1H-indol-3-yl)-propan-1-one claim 1 , and (−)-1-(2 claim 1 ,8-dimethyl-1-oxa-3 claim 1 ,8-diazaspiro[4.5]dec-3-yl)-3-(1H-indol-3-yl)-propan-1-one.28. A pharmaceutical composition comprising the compound AF710B and a pharmaceutically acceptable carrier claim 1 , excipient ...

Подробнее
Номер записи: 21
12-09-2013 дата публикации

COGNITIVE FUNCTION

Номер: US20130236447A1
Автор: ROSENBLUM Yaacov, SEGEV Yifat, STERN Elad
Принадлежит: CARMEL-HAIFA UNIVERSITY ECONOMIC CORP., LTD.

Inhibition of eIF-2α phosphorylation can be used to improve cognitive function and/or to treat dementia, including Alzheimer's Disease. In particular, this can be achieved by inhibiting the kinase activity of PKR in a non-toxic manner. 1. A method for improving cognitive function , said method comprising administering to a patient in need a therapeutically effective amount of an inhibitor of eIF-2α phosphorylation or a pharmaceutically acceptable salt thereof such as to improve cognitive function in said patient.2. The method according to claim 1 , for improving learning claim 1 , improving memory formation claim 1 , or both.3. The method according to claim 2 , for treating dementia in said patient.4. The method according to claim 3 , for treating Alzheimer's Disease.5. The method according to claim 1 , wherein the inhibitor of eIF-2α phosphorylation inhibits a kinase.6. The method according to claim 5 , wherein the inhibitor is an inhibitor of the kinase activity of PKR.7. The method according to claim 5 , wherein the inhibitor acts to inhibit the ATP-binding site of a kinase.8. The method according to claim 1 , wherein the inhibitor is administered orally or by injection.9. The method according to claim 1 , wherein the inhibitor is a small molecule.11. The method according to claim 1 , wherein the inhibitor is a protein claim 1 , a peptide claim 1 , an antibody or a nucleic acid.12. The method according to claim 11 , wherein the nucleic acid is an antisense RNA or a double stranded RNA.13. The method according to claim 1 , including inhibiting an eIF-2α kinase.14. The method according to claim 1 , including inhibiting the kinase activity of PKR.15. The method according to claim 1 , wherein the patient is human. The present application is a Continuation-in-Part of U.S. patent application Ser. No. 12/827,935, filed Jun. 30, 2010, which is a National stage and Continuation-in-Part of International Application No. PCT/IB2009/007857, filed Dec. 21, 2009, in which the ...

Подробнее
Номер записи: 22
12-09-2013 дата публикации

Synthesis of polycyclic alkaloids

Номер: US20130237524A1
Автор: Dane Goff, Donald G. Payan, Sylvia Braselmann
Принадлежит: Rigel Pharmaceuticals Inc

Disclosed embodiments concern polycyclic alkaloid compounds and methods for their use and synthesis. Particular embodiments concern polycyclic alkaloids having a fused, six-membered ring, while other embodiments concern polycyclic alkaloids having a fused, five-membered ring. Methods for making the polycyclic alkaloids are disclosed, as well as methods for their use as prophylactics or treatments for certain diseases. Also disclosed are pharmaceutical compositions comprising the polycyclic alkaloids and their use.

Подробнее
Номер записи: 23
26-09-2013 дата публикации

NOVEL FUSED PYRAZOLE DERIVATIVES AND THEIR USE AS ALLOSTERIC MODULATORS OF METABOTROPIC GLUTAMATE RECEPTORS

Номер: US20130252944A1
Автор: Boléa Christelle, Celanire Sylvain, Dong Jingchao, Jones Philip, Ju Yi, Kong Yanling, Lei Zhiyu, Liu Fuqing, Liverton Nigel J., Luo Yunfu, Soll Richard, Tang Lam, Wei Jieping, Wei Qiaoxin, Zhang Haoyong, Zhang Minxiang
Принадлежит:

The present invention relates to novel compounds of Formula (I), wherein M, A and Y are defined as in Formula (I); invention compounds are modulators of metabotropic glutamate receptors—subtype 4 (“mGluR”) which are useful for the treatment or prevention of central nervous system disorders as well as other disorders modulated by mGluRreceptors. The invention is also directed to pharmaceutical compositions and the use of such compounds in the manufacture of medicaments, as well as to the use of such compounds for the prevention and treatment of such diseases in which mGluRis involved. 3. A compound according to having the Formula (II) wherein:{'sup': 1', '2', '1', '2', '3', '4', '1', '2', '3', '4', '5', '6', '1', '2', '3', '4', '5', '6', '7', '8, 'Y is selected from the group of —CRR—, —CRR—CRR—, —CRR—CRR—CRR— and —CRR—CRR—CRR—CRR;'}{'sup': 1', '2', '3', '4', '5', '6', '7', '8, 'sub': 3', '1', '6', '1', '6', '3', '7', '1', '6', '1', '6', '1', '6', '0', '6', '0', '6', '2', '1', '6', '0', '6', '1', '6', '0', '6', '2, 'R, R, R, R, R, R, Rand Rare each independently selected from the group of hydrogen, halogen, —CN, —CFor an optionally substituted radical selected from the group of —(C-C)alkyl, —(C-C)haloalkyl, —(C-C)cycloalkyl, aryl, heteroaryl, heterocycle, —(C-C)allylene-aryl, —(C-C)alkylene-heteroaryl, —(C-C)alkylene-heterocycle, —O—(C-C)alkyl, —N—((C-C)alkyl), —(C-C)alkyl-O—(C-C)alkyl, and —(C-C)alkyl-N—((C-C)alkyl);'}{'sup': 1', '2', '3', '4', '5', '6', '7', '8, 'Any two radicals of R (R, R, R, R, R, R, Ror R) may be taken together to form an optionally substituted 3 to 10 membered carbocyclic or heterocyclic ring;'}provided that according to proviso (i) the compound is not:N-(Pyridin-2-yl)-5,6-dihydro-4H-thiazolo[4,5-e]indazol-2-amineN-(6-Methylpyridin-2-yl)-5,6-dihydro-4H-thiazolo[4,5-e]indazol-2-amineN-(6-Chloropyridin-2-yl)-5,6-dihydro-4H-thiazolo[4,5-e]indazol-2-amineN-(6-Fluoropyridin-2-yl)-5,6-dihydro-4H-thiazolo[4,5-e]indazol-2-amine4-Methyl-N-(pyridin-2-yl ...

Подробнее
Номер записи: 24
26-09-2013 дата публикации

SPIRO-OXINDOLE COMPOUNDS AND THEIR USE AS THERAPEUTIC AGENTS

Номер: US20130252962A1
Автор: Cadieux Jean-Jacques Alexandre, Chafeev Mikhail, CHAKKA Nagasree, Chowdhury Sultan, CIKOJEVIC Zoran, DOUGLAS Amy Frances, FRASER Lauren, Fu Jianmin, GAUTHIER Simon J., Hsieh Tom, Jia Qi, LANGILLE Jonathan, Liu Shifeng, Sun Jianyu, Sun Shaoyi, Sviridov Serguei, Wood Mark, ZENOVA Alla Yurevna
Принадлежит:

This invention is directed to spiro-oxindole compounds, as stereoisomers, enantiomers, tautomers thereof or mixtures thereof; or pharmaceutically acceptable salts, solvates or prodrugs thereof, for the treatment and/or prevention of sodium channel-mediated diseases or conditions, such as pain. 13.-. (canceled)5. The compound of selected from:1′-(pyridin-2-ylmethyl)spiro[furo[2,3-g]quinoxaline-8,3′-indol]-2′(1′H)-one;1-(diphenylmethyl)spiro[indole-3,3′-thieno[2,3-f][1]benzofuran]-2(1′H)-one;1-(diphenylmethyl)spiro[indole-3,3′-thieno[2,3-f][1]benzofuran]-2(1′H)-one 5,5′-dioxide;spiro[indole-3,3′-thieno[2,3-f][1]benzofuran]-2(1′H)-one 5,5′-dioxide; or1-(pyridin-2-ylmethyl)spiro[indole-3,3′-thieno[2,3-f][1]benzofuran]-2(1′H)-one 5,5′-dioxide.1′-(4-methoxybenzyl)-3-methylspiro[furo[2,3-f][1,2]benzisoxazole-7,3′-indol]-2′(1′H)-one;5-(benzyloxy)-1′-[(5-chloro-2-thienyl)methyl]spiro[1-benzofuran-3,3′-indol]-2′(1′H)-one;1′-(diphenylmethyl)-6-methoxy-5-methylspiro[1-benzofuran-3,3′-indol]-2′(1′H)-one;6-bromo-1′-(diphenylmethyl)spiro[1-benzofuran-3,3′-indol]-2′(1′H)-one;1′-(diphenylmethyl)-5,6-dimethylspiro[1-benzofuran-3,3′-indol]-2′(1′H)-one;6-(benzyloxy)-1′-(diphenylmethyl)spiro[1-benzofuran-3,3′-indol]-2′(1′H)-one;1′-(diphenylmethyl)-5-fluoro-6-methoxyspiro[1-benzofuran-3,3′-indol]-2′(1′H)-one;1′-(diphenylmethyl)-5-fluorospiro[1-benzofuran-3,3′-indol]-2′(1′H)-one;1′-(diphenylmethyl)-6-methoxyspiro[1-benzofuran-3,3′-indol]-2′(1′H)-one;6-(benzyloxy)-1′-(3-methylbutyl)spiro[1-benzofuran-3,3′-indol]-2′(1′H)-one;6-bromo-1′-{[5-(trifluoromethyl)furan-2-yl]methyl}spiro[1-benzofuran-3,3′-indol]-2′(1H)-one;5-bromo-1-{[5-(trifluoromethyl)furan-2-yl]methyl}spiro[1-benzofuran-3,3′-indol]-2′(1′H)-one;6-methoxy-5-methylspiro[1-benzofuran-3,3′-indol]-2′(1′H)-one;6-bromospiro[1-benzofuran-3,3′-indol]-2′(1′H)-one;5,6-dimethylspiro[1-benzofuran-3,3′-indol]-2′(1′H)-one;5-fluoro-6-methoxyspiro[1-benzofuran-3,3′-indol]-2′(1′H)-one;5-fluoro-spiro[1-benzofuran-3,3′-indol]-2′(1′H)-one;6- ...

Подробнее
Номер записи: 25
03-10-2013 дата публикации

BICYCLIC OXAZOLE AND THIAZOLE COMPOUNDS AND THEIR USE AS ALLOSTERIC MODULATORS OF MGLUR5 RECEPTORS

Номер: US20130261107A1
Автор: ALCAZAR VACA Manuel Jesus, Bartolomé-Nebreda José Manuel, Conde-Ceide Susana, Conn P. Jeffrey, Jones Carrie K., Lindsley Craig W., MacDonald James Gregor, Stauffer Shaun R.
Принадлежит: VANDERBILT UNIVERSITY

In one aspect, the invention relates to novel bicyclic oxazole and thiazole compounds which are positive allosteric modulators of the metabotropic glutamate receptor subtype 5 (“mGluR5”); synthetic methods for making the compounds; pharmaceutical compositions comprising the compounds; methods of treating neurological and psychiatric disorders associated with glutamate dysfunction using the compounds and compositions; and methods for the treatment or prevention of disorders associated with glutamate dysfunction and diseases in which the mGluR5 subtype of receptors is involved. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention. 2. The compound of claim 1 , wherein -A-A- is selected from —OCH— claim 1 , —CHCH— claim 1 , and —CH═CH—.3. The compound of claim 1 , wherein claim 1 , Ris six-membered monocyclic aryl or six-membered monocyclic heteroaryl.4. The compound of claim 3 , wherein claim 3 , Ris selected from phenyl claim 3 , pyridinyl claim 3 , pyrazinyl claim 3 , pyridazinyl and pyrimidinyl claim 3 , and substituted with 0 claim 3 , 1 claim 3 , 2 claim 3 , or 3 groups each independently selected from halo claim 3 , C1-4-alkyl claim 3 , C1-4-alkyloxy claim 3 , monohalo-C1-4-alkyl claim 3 , and polyhalo-C1-4-alkyl.5. The compound of claim 1 , wherein the compound exhibits positive allosteric modulation of mGluR5 response.6. The compound of claim 1 , wherein the compound exhibits potentiation of mGluR5 response to glutamate as an increase in response to non-maximal concentrations of glutamate in human embryonic kidney cells transfected with mGluR5 in the presence of the compound claim 1 , compared to the response to glutamate in the absence of the compound.7. The compound of claim 1 , wherein Z is O.8. The compound of claim 1 , wherein:{'sup': '1', 'sub': 1-4', '1-4', '1-4, 'Ris phenyl substituted with 0, 1, 2, or 3 groups each independently selected from halo, ...

Подробнее
Номер записи: 26
03-10-2013 дата публикации

TETRAHYDROPYRROLOTHIAZINE COMPOUNDS

Номер: US20130261111A1
Автор: BECK James Peter, GREEN Steven James, JR Leonard Larry, LOPEZ Jose Eduardo, MATHES Brian Michael, MERGOTT Dustin James, PORTER Warren Jaye, RANKOVIC Zoran, SHI Yuan, WATSON Brian Morgan, WINNEROSKI
Принадлежит: ELI LILLY AND COMPANY

The present invention provides compounds of Formula I: 110-. (canceled)1318-. (canceled) The present invention relates to novel tetrahydropyrrolothiazine compounds, to pharmaceutical compositions comprising the compounds, to methods of using the compounds to treat physiological disorders, and to intermediates and processes useful in the synthesis of the compounds.The present invention is in the field of treatment of Alzheimer's disease and other diseases and disorders involving amyloid β (Aβ) peptide, a neurotoxic and highly aggregatory peptide segment of the amyloid precursor protein (APP). Alzheimer's disease is a devastating neurodegenerative disorder that affects millions of patients worldwide. In view of the currently approved agents on the market which afford only transient, symptomatic benefits to the patient, there is a significant unmet need in the treatment of Alzheimer's disease.Alzheimer's disease is characterized by the generation, aggregation, and deposition of Aβ in the brain. Complete or partial inhibition of β-secretase (β-site amyloid precursor protein-cleaving enzyme; BACE) has been shown to have a significant effect on plaque-related and plaque-dependent pathologies in mouse models suggesting that even small reductions in Aβ peptide levels might result in a long-term significant reduction in plaque burden and synaptic deficits, thus providing significant therapeutic benefits, particularly in the treatment of Alzheimer's disease.US 2009/0209755 discloses fused aminodihydrothiazine derivatives which possess BACE inhibitory activity and are further disclosed as useful therapeutic agents for a neurodegenerative disease caused by Aβ peptide, such as Alzheimer's type dementia. In addition, 31(46), pages 16507-16516 (2011) discloses (S)-4-(2,4-difluoro-5-pyrimidin-5-yl-phenyl)-4-methyl-5,6-dihydro-4H-[1,3]thiazin-2-ylamine, an orally available CNS-active BACE inhibitor.BACE inhibitors that are potent and efficacious with sufficient CNS penetration are ...

Подробнее
Номер записи: 27
10-10-2013 дата публикации

Macrocyclic Indoles as Hepatitis C Virus Inhibitors

Номер: US20130267511A1
Автор: Hu Lili, Nyanguile Origene, Raboisson Pierre Jean-Marie Bernard, Vendeville Sandrine
Принадлежит:

The present invention relates to inhibitors of HCV replication of formula (I), the N-oxide forms, the pharmaceutically acceptable addition salts, the quaternary amines and the stereochemically isomeric forms thereof, 7. A compound according to claim 1 , wherein each of c claim 1 , d claim 1 , e claim 1 , f claim 1 , g claim 1 , and h claim 1 , is claim 1 , independently claim 1 , 0 claim 1 , 1 claim 1 , 2 claim 1 , or 3 claim 1 , with the proviso that the macrocycle formed by the bivalent chain R claim 1 , the —C(═O)—NH— moiety to which Ris attached and the nitrogen and carbon atoms N1 claim 1 , C6 claim 1 , C7 claim 1 , and C7′ of the indole ring claim 1 , has from 14 to 16 member atoms.8. A compound according to claim 1 , wherein Ris hydrogen or Calkyl.9. A pharmaceutical composition comprising an anti-virally effective amount of a compound as claimed in and a pharmaceutically acceptable carrier.1015.-. (canceled) The present invention is concerned with macrocyclic indoles having inhibitory activity on the replication of the hepatitis C virus (HCV). It further concerns compositions comprising these compounds as active ingredients as well as processes for preparing these compounds and compositions.Hepatitis C virus is the leading cause of chronic liver disease worldwide and has become a focus of considerable medical research. HCV is a member of the Flaviviridae family of viruses in the hepacivirus genus, and is closely related to the genus, which includes a number of viruses implicated in human disease, such as dengue virus and yellow fever virus, and to the animal pestivirus family, which includes bovine viral diarrhoea virus (BVDV). HCV is a positive-sense, single-stranded RNA virus, with a genome of around 9,600 bases. The genome comprises both 5′ and 3′ untranslated regions which adopt RNA secondary structures, and a central open reading frame that encodes a single polyprotein of around 3,010-3,030 amino acids. The polyprotein encodes ten gene products which ...

Подробнее
Номер записи: 28
17-10-2013 дата публикации

POLY (ADP-RIBOSE) POLYMERASE (PARP) INHIBITORS

Номер: US20130274239A1
Автор: Gangloff Anthony R., Jennings Andrew John, Jones Benjamin, Kiryanov Andre A. A.
Принадлежит:

Disclosed are compounds of the following formula: 2. (canceled)5. The compound claim 3 , tautomer or pharmaceutically acceptable salt thereof according to claim 3 , wherein each Ris independently selected from the group consisting of hydrogen claim 3 , halo claim 3 , and (C)alkyl.7. The compound claim 6 , tautomer or pharmaceutically acceptable salt according to claim 6 , wherein each Ris independently selected from the group consisting of hydrogen claim 6 , halo claim 6 , and (C)alkyl.10. The compound claim 8 , tautomer or pharmaceutically acceptable salt according to claim 8 , wherein each Ris independently selected from the group consisting of hydrogen claim 8 , halo claim 8 , and (C)alkyl.12. The compound claim 11 , tautomer or pharmaceutically acceptable salt according to claim 11 , wherein each Ris independently selected from the group consisting of hydrogen claim 11 , halo claim 11 , and (C)alkyl.13. The compound claim 1 , tautomer or pharmaceutically acceptable salt according to claim 1 , wherein Ris selected from (C)alkyl and aryl(C)alkyl.1417-. (canceled)18. The compound claim 1 , tautomer or pharmaceutically acceptable salt according to claim 1 , wherein Rand Rare each independently selected from hydrogen claim 1 , halo claim 1 , and (C)alkyl.19. The compound claim 1 , tautomer or pharmaceutically acceptable salt according to claim 1 , wherein X is O.20. The compound claim 1 , tautomer or pharmaceutically acceptable salt according to claim 1 , wherein X is NR claim 1 , and Ris selected from the group consisting of hydrogen and (C)alkyl.2122-. (canceled)23. The compound claim 1 , tautomer or pharmaceutically acceptable salt according to claim 1 , wherein Lis —CH—.26. (canceled)29. The compound claim 27 , tautomer or pharmaceutically acceptable salt according to claim 27 , wherein{'sub': 23', '1-3', '3-6, 'Ris selected from hydrogen, (C)alkyl, and (C)cycloalkyl;'}{'sub': 26a', '26b', '1-3', '1-3, 'Rand Rare each independently selected from hydrogen, halo, ( ...

Подробнее
Номер записи: 29
31-10-2013 дата публикации

ARTHROPOD PEST CONTROL COMPOSITION AND METHOD FOR CONTROLLING ARTHROPOD PESTS

Номер: US20130289052A1
Автор: Iwata Atsushi, Sakamoto Emiko, Sakamoto Norihisa
Принадлежит: Sumitomo Chemical Company, Limited

Disclosed is an arthropod pest control composition having an excellent controlling effect on arthropod pests, which comprises a compound represented by formula (I): 2. The arthropod pest control composition according to claim 1 , wherein the weight ratio of the compound represented by formula (I) to metalaxyl or metalaxyl M is 10 claim 1 ,000:1 to 0.01:1.3. A method for controlling arthropod pests claim 1 , which comprises applying an effective amount of the arthropod pest control composition according to to plants or area in which plants are grown.4. The method for controlling arthropod pests according to claim 3 , wherein the plants or area in which plants are grown is the seeds of plants. The present application was filed claiming the priority of the Japanese Patent Application No. 2010-289610, the entire contents of which are herein incorporated by the reference.The present invention relates to an arthropod pest control composition and a method for controlling arthropod pests.Heretofore, various compounds are known as active ingredients in arthropod pest control compositions (see, for example, Patent Literature 1 and Non-Patent Literature 1).An object of the present invention is to provide an arthropod pest control composition having an excellent control effect on arthropod pests.The present inventors have intensively studied for providing an arthropod pest control composition having an excellent control effect on arthropod pests, and finally found that a composition comprising a compound represented by formula (I) as described below and metalaxyl or metalaxyl M has an excellent control effect on arthropod pests, thereby attaining the present invention.The present invention provides:[1] An arthropod pest control composition comprising a compound represented by formula (I):wherein,Q represents CR═CR, S, O or NCH,Rrepresents a halogen atom, cyano, nitro, an optionally halogenated C1-C4 alkyl group, an optionally halogenated C2-C4 alkenyl group, an optionally ...

Подробнее
Номер записи: 30
31-10-2013 дата публикации

PHARMACEUTICAL COMPOSITIONS COMPRISING POLYMORPHIC FORMS ALPHA, BETA, AND GAMMA OF RIFAXIMIN

Номер: US20130289269A1
Автор: Braga Dario, Campana Manuela, Cannata Vincenzo, Confortini Donatella, Righi Paolo, Rosini Goffredo, Viscomi Giuseppe Claudio
Принадлежит: ALFA WASSERMANN, S.P.A.

Crystalline polymorphous forms of rifaximin (INN), referred to as rifaximin α and rifaximin β, and a poorly crystalline form referred to as rifaximin γ, useful in the production of medicaments containing rifaximin for oral and topical use and obtained by means of a crystallization process carried out by hot-dissolving the raw rifaximin in ethyl alcohol and by causing the crystallization of the product by addition of water at a fixed temperature and for a fixed period of time, followed by a drying under controlled conditions until reaching a precise water content in the end product, are the object of the invention. 1. A pharmaceutical composition comprising rifaximin in polymorphic form α.2. A pharmaceutical composition comprising rifaximin in polymorphic form β.3. A pharmaceutical composition comprising rifaximin in polymorphic form γ. This application is a continuation of U.S. application Ser. No. 13/041,347, filed Mar. 4, 2011, now U.S. Pat. No. 8,158,644, issued on Apr. 17, 2012, which in turn is a continuation of U.S. application Ser. No. 12/119,622, filed May 13, 2008, now U.S. Pat. No. 7,906,542, issued on Mar. 15, 2011, which in turn is a continuation-in-part of application U.S. application Ser. No. 11/873,841, filed on Oct. 17, 2007, now U.S. Pat. No. 7,915,275, issued on Mar. 29, 2011, which is a continuation-in part of U.S. application Ser. No. 11/135,651, filed on May 24, 2005, now abandoned, which is a continuation-in-part of PCT/EP04/12490, filed on Nov. 4, 2004, which claims priority to Italian application No. MI2003A002144 filed Nov. 7, 2003, all of which are incorporated by reference herein in their entirety, including any drawings.1. Field of the InventionThe present invention relates to rifaximin polymorphic forms α, β and γ, the processes for their preparation and the use thereof in the manufacture of medicinal preparations.2. Description of the Related ArtRifaximin (INN; see The Merck Index, XIII Ed., 8304) is an antibiotic belonging to the ...

Подробнее
Номер записи: 31
07-11-2013 дата публикации

SELECTIVE GLYCOSIDASE INHIBITORS AND USES THEREOF

Номер: US20130296301A1
Автор: Chang Jiang, LIU Kun, McEachern Ernest J., Mu Changwei, Selnick Harold G., Shi Feng, Vocadlo David J., Wang Yaode, Wei Zhongyong, Zhou Yuanxi, Zhu Yongbao
Принадлежит:

The invention is directed to compounds for selectively inhibiting glycosidases, uses of the compounds and pharmaceutical compositions including the compounds, and methods of treating diseases and disorders related to deficiency or overexpression of O-GlcNAcase, and/or accumulation or deficiency of O-GlcNAc.

Подробнее
Номер записи: 32
21-11-2013 дата публикации

POLYMORPHOUS FORMS OF RIFAXIMIN, PROCESSES FOR THEIR PRODUCTION AND USE THEREOF IN THE MEDICINAL PREPARATIONS

Номер: US20130310410A1
Автор: Barbanti Maria Miriam, Braga Dario, Campana Manuela, Confortini Donatella, Viscomi Giuseppe Claudio
Принадлежит: ALFA WASSERMANN, S.P.A.

Crystalline polymorphous forms of the rifaximin (INN) antibiotic named rifaximin δ and rifaximin ε useful in the production of medicinal preparations containing rifaximin for oral and topical use and obtained by means of a crystallization process carried out by hot-dissolving the raw rifaximin in ethyl alcohol and by causing the crystallization of the product by addition of water at a determinate temperature and for a determinate period of time, followed by a drying carried out under controlled conditions until reaching a settled water content in the end product, are the object of the invention. 1. Rifaximin in polymorphic form δ , wherein the rifaximin polymorphic form δ has x-ray powder diffraction pattern peaks at about 5.7°±0.2 , 12.1°±0.2 , and 17.0°±0.2 2-θ.2. The rifaximin in polymorphic form δ of claim 1 , wherein the x-ray powder diffraction pattern further comprises a peak at about 11.3°±0.2 2-θ.3. The rifaximin in polymorphic form δ of claim 1 , wherein the x-ray powder diffraction pattern further comprises peaks at about 7.1°±0.2 and 21.5°±0.2 2-θ.4. The rifaximin in polymorphic form δ of claim 1 , wherein the x-ray powder diffraction pattern further comprises peaks at about 6.7°±0.2 and 8.7°±0.2 2-θ.5. The rifaximin in polymorphic form δ of claim 1 , wherein the polymorph has x-ray powder diffraction pattern peaks at about 5.7°±0.2 claim 1 , 6.7°±0.2 claim 1 , 7.1°±0.2 claim 1 , 8.0°±0.2 claim 1 , 8.7°±0.2 claim 1 , 10.4°±0.2 claim 1 , 11.3°±0.2 claim 1 , 12.1°±0.2 claim 1 , 17.0°±0.2 claim 1 , 17.3°±0.2 claim 1 , 17.5°±0.2 claim 1 , 18.5°±0.2 claim 1 , 18.8°±0.2 claim 1 , 19.1°±0.2 claim 1 , 21.0°±0.2 and 21.5°±0.2 2-θ.6. The rifaximin in polymorphic form δ of claim 1 , wherein the polymorph δ has a water content of between 3% and 4.5%.7. The rifaximin in polymorphic form δ of claim 1 , wherein the polymorph δ has a water content of between 2.5% and 6%.8. Rifaximin in polymorphic form ε claim 1 , wherein the rifaximin polymorphic form ε has x-ray ...

Подробнее
Номер записи: 33
21-11-2013 дата публикации

Inhibitors of hcv ns5a protein

Номер: US20130310427A1
Автор: Leping Li, Min Zhong
Принадлежит: Presidio Pharmaceuticals Inc

Antiviral compounds may be used to inhibit or reduce the activity of Hepatitis C virus (HCV), particularly HCV's NS5A protein. In these contexts, inhibition and reduction of activity of the NS5A protein refers to a lower level of the measured activity relative to a control experiment in which the cells or the subjects are not treated with the test compound. The inhibition or reduction in the measured activity is at least a 10% reduction or inhibition. The compounds and their isomeric forms and pharmaceutically acceptable salts thereof are useful in treating and preventing HCV infection alone or when used in combination with other compounds targeting viral or cellular elements or functions involved in the HCV lifecycle.

Подробнее
Номер записи: 34
28-11-2013 дата публикации

INHIBITORS OF BETA-SECRETASE

Номер: US20130317014A1
Автор: Dillard Lawrence W., Jia Lanqi, YUAN Jing, ZHENG Yajun
Принадлежит:

The present invention is directed to a compound represented by the following structural formula: 156-. (canceled)58. The method of claim 57 , wherein the disorder is selected from the group consisting of Alzheimer's disease claim 57 , cognitive impairment claim 57 , Down's Syndrome claim 57 , HCHWA-D claim 57 , cognitive decline claim 57 , senile dementia claim 57 , cerebral amyloid angiopathy claim 57 , degenerative dementia claim 57 , other neurodegenerative disorders claim 57 , and glaucoma.5963-. (canceled)66. The method of claim 65 , wherein X is —O— and Ris —H claim 65 , —Br claim 65 , —F claim 65 , (C-C)alkyl claim 65 , (C-C)cycloalkyl claim 65 , aryl claim 65 , heteroaryl claim 65 , phenoxy claim 65 , or benzyloxy claim 65 , each optionally substituted with 1 to 3 substituents independently selected from the group consisting of —F claim 65 , —Cl claim 65 , —Br claim 65 , —CN claim 65 , —OR claim 65 , —NRR claim 65 , —S(O)R claim 65 , —NRS(═O)R claim 65 , —C(═O)OR claim 65 , —C(═O)NRR claim 65 , —NRC(═O)R claim 65 , —C(═S)NRR claim 65 , —C(═O)R claim 65 , (C-C)alkyl claim 65 , (C-C)cycloalkyl claim 65 , (C-C)alkenyl claim 65 , halo(C-C)alkyl claim 65 , (C-C)alkylsulfonylaminoalkyl claim 65 , hydroxy(C-C)alkyl claim 65 , cyano(C-C)alkyl claim 65 , (C-C)alkylcarbonylamino(C-C)alkyl claim 65 , (C-C)alkoxy claim 65 , halo(C-C)alkoxy claim 65 , (C-C)alkoxy(C-C)alkyl and a heteroaryl group.68. The method of claim 67 , wherein ring A is tetrahydrofuran claim 67 , tetrahydropyran claim 67 , cyclopentane claim 67 , cyclohexane claim 67 , cycloheptane claim 67 , oxepane claim 67 , 1 claim 67 ,3-dioxane claim 67 , piperidine claim 67 , 6 claim 67 ,7 claim 67 ,8 claim 67 ,9-tetrahydro-5H-benzo[7]annulene claim 67 , 2 claim 67 ,3-dihydro-1H-indene claim 67 , tetrahydronaphthalene claim 67 , decahydronaphthalene claim 67 , 5 claim 67 ,6 claim 67 ,7 claim 67 ,8-tetrahydroquinoline claim 67 , 5 claim 67 ,6 claim 67 ,7 claim 67 ,8-tetrahydroisoquinoline claim 67 , 2- ...

Подробнее
Номер записи: 35
28-11-2013 дата публикации

NEW FORMS OF RIFAXIMIN AND USES THEROF

Номер: US20130317225A1
Автор: Bevill Melanie Janelle, Houston Travis L., Parent Stephan D., Schultheiss Nathan Carl, Vlahova Petinka, Wu Yiduo
Принадлежит:

The present invention relates to new rifaximin forms kappa, theta, rifaximin:piperazine cocrystal 1 and rifaximin:piperazine cocrystal 2, methods of making same and to their use in medicinal preparations and therapeutic methods. 1. A Form kappa of rifaximin , a Form theta and/or a rifaximin:piperazine cocrystal.27111213. A compound according to claim 1 , wherein form kappa is characterized by an XRPD substantially similar to 1 claim 1 , 2 claim 1 , 3 claim 1 , 10 and 16 or is characterized by a DSC or TGA Thermogram substantially similar to claim 1 , claim 1 , claim 1 , and .3. A compound of claim 1 , wherein form kappa of rifaximin is characterized by the peaks listed in Table 3 or Table 4.4. A compound of claim 1 , wherein form kappa of rifaximin exhibits an X-ray powder diffraction pattern having characteristic peaks expressed in degrees 2θ (+/−0.10 degree θ) at (6.45-6.67)±0.20 claim 1 , (6.83-6.94)±0.20 and (7.68-7.78)±0.20; (6.45-6.67)±0.20 claim 1 , (6.83-6.94)±0.20 and (18.46-18.61)±0.20; (6.45-6.67)±0.20 claim 1 , (6.83-6.94)±0.20 and (7.52-7.56)±0.20; (6.83-6.94)±0.20 claim 1 , (7.68-7.78)±0.20 and (18.46-18.61)±0.20; (6.45-6.67)±0.20 claim 1 , (6.83-6.94)±0.20 claim 1 , (7.68-7.78)±0.20 and (18.46-18.61)±0.20; (6.83-6.94)±0.20 claim 1 , (7.52-7.56)±0.20 claim 1 , (7.68-7.78)±0.20 and (18.46-18.61)±0.20; (6.45-6.67)±0.20 claim 1 , (6.83-6.94)±0.20 claim 1 , (7.52-7.56)±0.20 claim 1 , (7.68-7.78)±0.20 and (18.46-18.61)±0.20; (6.45-6.67)±0.20 claim 1 , (6.83-6.94)±0.20 claim 1 , (7.52-7.56)±0.20 claim 1 , (7.68-7.78)±0.20 claim 1 , (8.30-8.34)±0.20 and (18.46-18.61)±0.20; or (5.41-5.65)±0.20 claim 1 , (6.45-6.67)±0.20 claim 1 , (6.83-6.94)±0.20 claim 1 , (7.52-7.56)±0.20 claim 1 , (7.68-7.78)±0.20 claim 1 , (8.30-8.34)±0.20 and (18.46-18.61)±0.20.5. A compound according to claim 1 , wherein the rifaximin:piperazine cocrystal is characterized by an XRPD substantially similar to .6. A compound according to claim 1 , wherein the rifaximin:piperazine cocrystal ...

Подробнее
Номер записи: 36
05-12-2013 дата публикации

N-(IMIDAZOLIDIN-2-YLIDENE)-HETEROCYCLOPENTA[b]PYRIDINE DERIVATIVES AS MODULATORS OF ALPHA 2 ADRENERGIC RECEPTORS

Номер: US20130324571A1
Автор: Chow Ken, Dibas Mohammed I., Garst Michael E., Sinha Santosh C., Wang Liming
Принадлежит:

The present invention relates to novel N-(imidazolidin-2-ylidene)-heterocyclo penta[b]pyridine derivatives, processes for preparing them, pharmaceutical compositions containing them and their use as pharmaceuticals. 2. The method according to claim 1 , wherein the disorder is a retinal disease selected from: age related macular degeneration claim 1 , wet macular degeneration claim 1 , dry macular degeneration claim 1 , geographic atrophy claim 1 , diabetic retinopathy claim 1 , diabetic macular edema claim 1 , tumors claim 1 , retinal vein occlusion claim 1 , ocular hypertension claim 1 , glaucoma claim 1 , retinitis pigmentosa and neuritis secondary to multiple sclerosis.3. The method according to claim 1 , wherein the disorder is a skin condition selected from: rosacea claim 1 , sunburn claim 1 , psoriasis claim 1 , acne rosacea claim 1 , menopause-associated hot flashes claim 1 , hot flashes resulting from orchiectomyatopic dermatitis claim 1 , photoaging claim 1 , seborrheic dermatitis claim 1 , acne claim 1 , allergic dermatitis claim 1 , redness of the skin claim 1 , telangiectasia of the face claim 1 , rhinophymia claim 1 , red bulbous nose claim 1 , acne-like skin eruptions claim 1 , burning or stinging sensation of the face claim 1 , irritated and bloodshot and watery eyes claim 1 , erythema of the skin claim 1 , cutenous hyperactivity with dilation of blood vessels of the skin claim 1 , Lyell's syndrome claim 1 , Stevens-Johnson syndrome claim 1 , erythema multiforme minor and erythema multiforme major.4. The method according to claim 1 , wherein the disorder is glaucoma claim 1 , elevated intraocular pressure claim 1 , ischemic neuropathies claim 1 , optic neuropathy claim 1 , pain claim 1 , visceral pain claim 1 , corneal pain claim 1 , headache pain claim 1 , migraine claim 1 , cancer pain claim 1 , back pain claim 1 , irritable bowel syndrome pain claim 1 , muscle pain and pain associated with diabetic neuropathy claim 1 , diabetic retinopathy claim 1 ...

Подробнее
Номер записи: 37
12-12-2013 дата публикации

NOVEL FUSED THIAZOLO AND OXAZOLO PYRIMIDINONES

Номер: US20130331406A1
Автор: BADANTHADKA Murali, CHAUDHARI Anita, CHAUTHAIWALE Vijay, CHHIPA Laxmikant, DESHPANDE Shailesh, DUTT Chaitanya, GUPTA Ramesh Chandra, JAMADARKHANA Prashant G., MOHANAN Anookh, SRIVASTAVA Sanjay
Принадлежит: Torrent Pharmaceuticals Limited

The present invention relates to novel compounds, their pharmaceutically acceptable salts, and their isomers, steroisomers, conformers, tautomers, polymorphs, hydrates and solvates. The present invention also encompasses pharmaceutically acceptable compositions of said compounds and process for preparing novel compounds. The invention further relates to the use of the above-mentioned compounds for the preparation of medicament for use as pharmaceuticals. 2. The method of claim 1 , wherein the anemia comprises anemia of elderly or anemia associated with conditions like chronic diseases claim 1 , renal failure claim 1 , cancer claim 1 , infection claim 1 , dialysis claim 1 , surgery claim 1 , and chemotherapy.3. The method of claim 1 , wherein the compound of formula (I) is selected from the group consisting of:[(2-Hydroxy-4-oxo-5,6,7,8-tetrahydro-4H-9-thia-1,4-a-diaza-fluorene-3-carbonyl)-amino]-acetic acid;3-(Carboxymethyl-carbamoyl)-2-hydroxy-4-oxo-5,8-dihydro-4H,6H-9-thia-1,4a,7-triaza-fluorene-7-carboxylic acid ethyl ester;[(2-Hydroxy-7-methanesulfonyl-4-oxo-5,6,7,8-tetrahydro-4H-9-thia-1,4a,7-triaza-fluorene-3-carbonyl)-amino]-acetic acid;{[2-Hydroxy-7-(3-methyl-butyryl)-4-oxo-5,6,7,8-tetrahydro-4H-9-thia-1,4a,7-triaza-fluorene-3-carbonyl]-amino}-acetic acid;{[2-Hydroxy-4-oxo-7-(propane-2-sulfonyl)-5,6,7,8-tetrahydro-4H-9-thia-1,4a,7-triaza-fluorene-3-carbonyl]-amino}-acetic acid;1-[(2-Hydroxy-4-oxo-5,6,7,8-tetrahydro-4H-9-thia-1,4-a-diaza-fluorene-3-carbonyl)-amino]-cyclopentanecarboxylic acid;{[2-Hydroxy-4-oxo-7-(toluene-4-sulfonyl)-5,6,7,8-tetrahydro-4H-9-thia-1,4a,7-triaza-fluorene-3-carbonyl]-amino}-acetic acid;[(2-Hydroxy-4-oxo-7-phenylcarbamoyl-5,6,7,8-tetrahydro-4H-9-thia-1,4a,7-triaza-fluorene-3-carbonyl)-amino]-acetic acid;[(7-Cyclopropanecarbonyl-2-hydroxy-4-oxo-5,6,7,8-tetrahydro-4H-9-thia-1,4a,7-triaza-fluorene-3-carbonyl)-amino]-acetic acid;[(2-Hydroxy-4-oxo-6,7,8,9-tetrahydro-4H,5H-10-thia-1,4-a-diaza-benzo[a]azulene-3-carbonyl)-amino]-acetic acid ...

Подробнее
Номер записи: 38
02-01-2014 дата публикации

SELECTIVE GLYCOSIDASE INHIBITORS AND USES THEREOF

Номер: US20140005191A1
Автор: Coburn Craig A., LIU Kun, McEacher Ernest J., Mu Changwei, Selnick Harold G., Vocadlo David J., Wang Yaode, Wei Zhongyong, Zhou Yuanxi
Принадлежит:

The invention provides compounds for selectively inhibiting glycosidases, prodrugs of the compounds, and pharmaceutical compositions including the compounds or prodrugs of the compounds. The invention also provides methods of treating diseases and disorders related to deficiency or overexpression of O-GlcNAcase, accumulation or deficiency of O-GlcNAc. 2. The compound of wherein Ris H or C(O)CH;4. The compound of wherein Ris OH claim 1 , NH(cyclopropyl) claim 1 , NH(cyclopentyl) claim 1 , O(CO)NH(CHCH) claim 1 , O(CO)N(CH) claim 1 , O(CO)N(CHCH) claim 1 , or O(CO)CH.6. (canceled)7. The compound of wherein the compound is selected from the following group:(3aR,5R,6S,7R,7aR)-2-(azetidin-1-yl)-5-(hydroxymethyl)-5,6,7,7a-tetrahydro-3aH-pyrano[3,2-d]thiazole-6,7-diol;(3aR,5R,6S,7R,7aR)-5-(acetoxymethyl)-2-(azetidin-1-yl)-5,6,7,7a-tetrahydro-3aH-pyrano[3,2-d]thiazole-6,7-diyl diacetate;(3aR,5R,6S,7R,7aR)-2-(3-fluoroazetidin-1-yl)-5-(hydroxymethyl)-5,6,7,7a-tetrahydro-3aH-pyrano[3,2-d]thiazole-6,7-diol;(3aR,5R,6S,7R,7aR)-2-(3-hydroxyazetidin-1-yl)-5-(hydroxymethyl)-5,6,7,7a-tetrahydro-3aH-pyrano[3,2-d]thiazole-6,7-diol;(3aR,5R,6S,7R,7aR)-5-(hydroxymethyl)-2-(3-methoxyazetidin-1-yl)-5,6,7,7a-tetrahydro-3aH-pyrano[3,2-d]thiazole-6,7-diol;(3aR,5R,6S,7R,7aR)-5-(hydroxymethyl)-2-(pyrrolidin-1-yl)-5,6,7,7a-tetrahydro-3aH-pyrano[3,2-d]thiazole-6,7-diol;(3aR,5R,6S,7R,7aR)-5-(acetoxymethyl)-2-(pyrrolidin-1-yl)-5,6,7,7a-tetrahydro-3aH-pyrano[3,2-d]thiazole-6,7-diyl diacetate;(3aR,5R,6S,7R,7aR)-2-((S)-3-fluoropyrrolidin-1-yl)-5-(hydroxymethyl)-5,6,7,7a-tetrahydro-3aH-pyrano[3,2-d]thiazole-6,7-diol;(3aR,5R,6S,7R,7aR)-2-((R)-3-fluoropyrrolidin-1-yl)-5-(hydroxymethyl)-5,6,7,7a-tetrahydro-3aH-pyrano[3,2-d]thiazole-6,7-diol;(3aR,5R,6S,7R,7aR)-2-(3,3-difluoropyrrolidin-1-yl)-5-(hydroxymethyl)-5,6,7,7a-tetrahydro-3aH-pyrano[3,2-d]thiazole-6,7-diol;(3aR,5R,6S,7R,7aR)-5-(hydroxymethyl)-2-(piperidin-1-yl)-5,6,7,7a-tetrahydro-3aH-pyrano[3,2-d]thiazole-6,7-diol;(3aR,5R,6S,7R,7aR)-5-(hydroxymethyl ...

Подробнее
Номер записи: 39
09-01-2014 дата публикации

Fused Aminodihydrothiazine Derivatives

Номер: US20140011802A1
Автор: Dimopoulos Paschalis, Hall Adrian, Kita Yoichi, Madin Andrew, Shuker Nicola Louise
Принадлежит: Eisai R&D Management Co., Ltd.

The present invention relates to a fused aminodihydrothiazine derivative of formula (I): wherein R is hydrogen or Calkyl, optionally substituted by one to five halogen atoms; n is 0, 1, 2 or 3; Ar is phenyl or a 5- or 6-membered heteroaromatic group containing 1, 2 or 3 N atoms, which Ar is optionally substituted by one to three substituents selected from hal, hydroxyl, —CN, Calkyl, Calkenyl, Calkynyl,alkoxy, Ccycloalkoxy and pyrazine, where Calkyl and Calkoxy are optionally substituted by one to three halogen atoms; and pharmaceutically acceptable salts thereof; which compound has an Aβ production inhibitory effect or a BACE1 inhibitory effect and is useful as a prophylactic or therapeutic agent for a neurodegenerative disease 1 caused by Aβ and typified by Alzheimer-type dementia. 2. The compound or pharmaceutically acceptable salt thereof according to claim 1 , wherein R is methyl.3. The compound or pharmaceutically acceptable salt thereof according to claim 1 , wherein n is 1.4. The compound or pharmaceutically acceptable salt thereof according to claim 1 , wherein Ar is phenyl or a 5- or 6-membered heteroaromatic group containing 1 claim 1 , 2 or 3 N atoms claim 1 , which Ar is optionally substituted by one or two substituents selected from hal claim 1 , —CN claim 1 , Calkyl claim 1 , Calkoxy and pyrazine claim 1 , where Calkyl and Calkoxy are optionally substituted by one to three fluorine atoms.8. (canceled)9. A method of inhibiting beta-site amyloid-β precursor protein cleaving enzyme 1 (BACE1) claim 1 , comprising administering to a human subject an effective amount of the compound or pharmaceutically acceptable salt thereof according to .10. A method of treating a neurodegenerative disease claim 1 , comprising administering to a human subject suffering from the neurodegenerative disease an effective amount of the compound or pharmaceutically acceptable salt thereof according to .11. (canceled)12. A method of treating type 2 diabetes claim 1 , comprising ...

Подробнее
Номер записи: 40
16-01-2014 дата публикации

BENZOXAZEPINES AS INHIBITORS OF mTOR AND METHODS OF THEIR USE AND MANUFACTURE

Номер: US20140018347A1
Автор: Rice Kenneth
Принадлежит: Exelixis, Inc.

The invention is directed to inhibitors of mTOR and pharmaceutically acceptable salts or solvates thereof, as well as methods of using them. The inhibitors are generally of structural Formula (I) wherein the variables are as defined herein. 9. The compound of claim 1 , wherein Ris H claim 1 , (C-C)alkyl claim 1 , or NH.10. The compound of which is:6-(4-{2-[(dimethylamino)methyl]-5-ethyl-6-methylpyrimidin-4-yl}-2,3,4,5-tetrahydro-1,4-benzoxazepin-7-yl)[1,3]thiazolo[5,4-b]pyridin-2-amine;6-(4-{2-[(dimethylamino)methyl]-5,6-dimethylpyrimidin-4-yl}-2,3,4,5-tetrahydro-1,4-benzoxazepin-7-yl)[1,3]thiazolo[5,4-b]pyridin-2-amine;{4-[7-(2-amino[1,3]thiazolo[5,4-b]pyridin-6-yl)-2,3-dihydro-1,4-benzoxazepin-4(5H)-yl]-6-methyl-5-(1-methylethyl)pyrimidin-2-yl}methanol;6-(4-{2-[(diethylamino)methyl]-6-methyl-5-(1-methylethyl)pyrimidin-4-yl}-2,3,4,5-tetrahydro-1,4-benzoxazepin-7-yl)[1,3]thiazolo[5,4-b]pyridin-2-amine;6-[4-(2-amino-5,6-dimethylpyrimidin-4-yl)-2,3,4,5-tetrahydro-1,4-benzoxazepin-7-yl][1,3]thiazolo[5,4-b]pyridin-2-amine;6-[4-(2-amino-5-ethyl-6-methylpyrimidin-4-yl)-2,3,4,5-tetrahydro-1,4-benzoxazepin-7-yl][1,3]thiazolo[5,4-b]pyridin-2-amine;6-[4-(2-amino-6-chloro-5-ethylpyrimidin-4-yl)-2,3,4,5-tetrahydro-1,4-benzoxazepin-7-yl][1,3]thiazolo[5,4-b]pyridin-2-amine;6-{4-[2-amino-6-chloro-5-(1-methylethyl)pyrimidin-4-yl]-2,3,4,5-tetrahydro-1,4-benzoxazepin-7-yl}[1,3]thiazolo[5,4-b]pyridin-2-amine;6-[4-(2-amino-6-chloro-5-propylpyrimidin-4-yl)-2,3,4,5-tetrahydro-1,4-benzoxazepin-7-yl][1,3]thiazolo[5,4-b]pyridin-2-amine;6-{4-[2-amino-6-fluoro-5-(1-methylethyl)pyrimidin-4-yl]-2,3,4,5-tetrahydro-1,4-benzoxazepin-7-yl}[1,3]thiazolo[5,4-b]pyridin-2-amine;6-[4-(2-amino-6-chloro-5-ethenylpyrimidin-4-yl)-2,3,4,5-tetrahydro-1,4-benzoxazepin-7-yl][1,3]thiazolo[5,4-b]pyridin-2-amine;6-(4-{2-amino-6-methyl-5-[2-(methyloxy)ethyl]pyrimidin-4-yl}-2,3,4,5-tetrahydro-1,4-benzoxazepin-7-yl)[1,3]thiazolo[5,4-b]pyridin-2-amine;6-(4-{2-[(dimethylamino)methyl]-6-methyl-5-[2-(methyloxy)ethyl] ...

Подробнее
Номер записи: 41
30-01-2014 дата публикации

MACROCYCLIC COMPOUNDS AND METHODS OF TREATMENT

Номер: US20140031400A1
Автор: Kanchan Taori, Luesch Hendrik, Paul Valerie J.
Принадлежит: UNIVERSITY OF FLORIDA RESEARCH FOUNDATION, INC.

The instant invention describes macrocyclic compounds having therapeutic activity, and methods of treating disorders such as cancer, tumors and cell proliferation related disorders, or affect cell differentiation, dedifferentiation or transdifferentiation. 2. The compound of claim 1 , wherein Rand Rare H.3. The compound of wherein Ris isopropyl.4. (canceled)5. The compound of wherein the compound is largazole.6. The compound of claim 1 , wherein Ris alkyl.7. The compound of claim 6 , wherein Ris alkylC(O)—.816.-. (canceled)17. A method of treating a subject suffering from or susceptible to a cell proliferation related disorder or disease claim 6 , wherein the subject has been identified as in need of treatment for a cell proliferation related disorder or disease claim 6 , comprising administering to said subject in need thereof claim 6 , an effective amount of a compound or pharmaceutical composition of formula I claim 6 , such that said subject is treated for said disorder.18. The method of claim 17 , wherein the compound of formula I is one of Compounds 1-8.19. The method of claim 17 , wherein the disorder is cancer claim 17 , solid tumor claim 17 , colon cancer claim 17 , breast cancer claim 17 , bone claim 17 , brain and others (e.g. claim 17 , osteosarcoma claim 17 , neuroblastoma claim 17 , colon adenocarcinoma the like.20. The method of claim 17 , wherein the disorder is an angiogenesis disorder.21. The method of claim 17 , wherein the disorder is solid tumor.22. The method of claim 17 , wherein the subject is a mammal.23. The method of wherein the subject is a primate or human.2427.-. (canceled)28. The method of claim 17 , wherein the compound of formula I is administered intravenously claim 17 , intramuscularly claim 17 , subcutaneously claim 17 , intracerebroventricularly claim 17 , orally or topically.29. The method of claim 17 , wherein the compound of formula I is administered alone or in combination with one or more other therapeutics.30. The method of ...

Подробнее
Номер записи: 42
06-02-2014 дата публикации

NOVEL (HETEROCYCLE/CONDENSED PIPERIDINE)-(PIPERAZINYL)-1-ALKANONE OR (HETEROCYCLE/CONDENSED PYRROLIDINE)-(PIPERAZINYL)-1-ALKANONE DERIVATIVES AND USE THEREOF AS p75 INHIBITORS

Номер: US20140038946A1
Автор: BARONI Marco, BONO Françoise, DELBARY-GOSSART Sandrine, VERCESI Valentina
Принадлежит: SANOFI

The disclosure relates to (heterocycle-fused piperidine)-(piperazinyl)-1-alkanone derivatives and (heterocycle-fused pyrrolidine)-(piperazinyl)-1-alkanone derivatives of formula (I): 3. The method according to claim 1 , wherein for the compound of formula (I) or pharmaceutically acceptable salt thereof:n represents 1.5. The method according to claim 1 , wherein for the compound of formula (I) or pharmaceutically acceptable salt thereof:Y represents a nitrogen atom or a single or double bond.6. The method according to claim 1 , wherein for the compound of formula (I) or pharmaceutically acceptable salt thereof: X claim 1 , Xand Xrepresent a carbon claim 1 , nitrogen or sulphur atom claim 1 , wherein one or more of X claim 1 , Xand Xis other than a carbon atom.8. The method according to claim 1 , wherein the compound of formula (I) is selected from the group consisting of:1-(6,7-dihydro-4H-thieno[3,2-c]pyridin-5-yl)-2-[8-(5-fluoropyrimidin-2-yl)-3,8-diazabicyclo[3.2.1]oct-3-yl]ethanone;2-[8-(5-fluoropyrimidin-2-yl)-3,8-diazabicyclo[3.2.1]oct-3-yl]-1-(2-phenyl-6,7-dihydro-4H-thiazolo[5,4-c]pyridin-5-yl)ethanone;1-(2-chloro-7,8-dihydro-5H-[1,6]naphthyridin-6-yl)-2-[8-(5-fluoropyrimidin-2-yl)-3,8-diazabicyclo[3.2.1]oct-3-yl]ethanone;2-[8-(5-fluoropyrimidin-2-yl)-3,8-diazabicyclo[3.2.1]oct-3-yl]-1-(2-phenyl-2,4,6,7-tetrahydropyrazolo[4,3-c]pyridin-5-yl)ethanone;6-{3-[2-oxo-2-(2-phenyl-6,7-dihydro-4H-thiazolo[5,4-c]pyridin-5-yl)ethyl]-3,8-diazabicyclo[3.2.1]oct-8-yl}nicotinic acid methyl ester;6-{(3S,5R)-3,5-dimethyl-4-[2-oxo-2-(2-phenyl-6,7-dihydro-4H-thiazolo[5,4-c]pyridin-5-yl)ethyl]piperazin-1-yl}nicotinic acid;6-{3-[2-oxo-2-(2-phenyl-6,7-dihydro-4H-thiazolo[5,4-c]pyridin-5-yl)ethyl]-3,8-diazabicyclo[3.2.1]oct-8-yl}nicotinic acid;6-{(3S,5R)-3,5-dimethyl-4-[2-oxo-2-(2-phenyl-6,7-dihydro-4H-thiazolo[5,4-c]pyridin-5-yl)ethyl]piperazin-1-yl}nicotinic acid;2-[(2S,6R)-2,6-dimethyl-4-(5-trifluoromethylpyridin-2-yl)piperazin-1-yl]-1-(2-phenyl-6,7-dihydro-4H-thiazolo[5,4-c] ...

Подробнее
Номер записи: 43
13-02-2014 дата публикации

AMINO-OXAZINES AND AMINO-DIHYDROTHIAZINE COMPOUNDS AS BETA-SECRETASE MODULATORS AND METHODS OF USE

Номер: US20140045828A1
Автор: Chen Jian, Cheng Yuan, DINEEN Thomas, Epstein Oleg, HUMAN Jason, JUDD Tedd, Liu Qingyian, Lopez Patricia, Low Jonathan D., MARX Isaac E., Minatti Ana Elena, Paras Nick A., Potashman Michele, Powers Timothy, Qian Wenyuan, WEISS Matthew, White Ryan, Yang Bryant, ZHONG Wenge
Принадлежит:

The present invention comprises a new class of compounds useful for the modulation of Beta-secretase enzyme activity and for the treatment of Beta-secretase mediated diseases, including Alzheimer's disease (AD) and related conditions. In one embodiment, the compounds have a general Formula I 3. The compound of claim 1 , or a a stereoisomer claim 1 , tautomer or pharmaceutically acceptable salt thereof claim 1 , wherein{'sup': '1', 'Ais CH, CF or N;'}{'sup': '2', 'Ais CH, CF or N;'}{'sup': '3', 'Ais CH, CF or N;'}{'sup': '4', 'Ais CH, CF or N;'}{'sup': '5', 'Ais CH, CF, CBr or N;'}{'sup': '6', 'Ais CH, CF or N;'}{'sub': '2', 'X is —CH—, —O— or —S—;'}{'sub': 2', '2', '2, 'Y is —O—, —S— or —CH—, provided that (1) when X is —O— or —S—, then Y is —CH—, or (2) when X is —CH, then Y is —O— or —S—; and'}{'sub': 2', '2', '3', '3', '2', '3, 'Z is CH, CHF, CF, CH(CH), C(CH)or CH(CF).'}4. The compound of claim 1 , or a stereoisomer or pharmaceutically acceptable salt thereof claim 1 , wherein{'sup': 1', '4', '5', '8, 'sub': 3', '3', '3', '3', '3', '3, 'each of R, R, Rand R, independently, is H, F, Cl, CF, OCF, methyl, ethyl, CN, OH, OCH, SCH, NHCHor C(O)CH;'}{'sup': 2', '7', '9, 'sub': 1-6', '2-6', '2-6', '1-6', '1-6', '1-6', '1-3', '2', '3', '3', '1-6', '2-4', '2-4', '1-6', '1-6', '1-6', '1-3', '2, 'one of Rand R, independently, is F, Cl, Br, I, haloalkyl, haloalkoxyl, C-alkyl, Calkenyl, Calkynyl, CN, —OCalkyl, —SCalkyl, —NHCalkyl, —N(Calkyl), —NH-phenyl, —NH-benzyl, —Si(CH)or a ring selected from the group consisting of phenyl, pyridyl, pyrimidyl, pyrazinyl, pyridazinyl, triazinyl, thienyl, pyrazolyl, imidazolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, diazolyl, triazolyl, tetrazolyl, pyranyl, dihydropyranyl, tetrahydropyranyl, furanyl, dihydrofuranyl, tetrahydrofuranyl, pyrrolyl, dihydropyrrolyl, pyrrolidinyl, piperidinyl, piperazinyl, morpholinyl, azetidinyl, 8-oxo-3-aza-bicyclo[3.2.1]oct-3-yl, aza-bicyclo[2.2.1]hept-5-yl, 2-oxo-7-aza-[3,5]-spironon-7-yl, cyclopropyl ...

Подробнее
Номер записи: 44
27-02-2014 дата публикации

Chromene compound

Номер: US20140054520A1
Автор: Junji Momoda, Junji Takenaka, Kazuhiro Teranishi, Mitsuyoshi Sando, Shinobu Izumi, Toshiaki Takahashi
Принадлежит: Tokuyama Corp

A novel photochromic compound which develops a color of a neutral tint and has high color optical density, high fading speed and excellent durability. The present invention is a chromene compound having an indeno(2,1-f)naphtho(1,2-b)pyran structure as the basic skeleton in which a hetero ring having two hetero atoms including at least one sulfur atom is directly bonded to the 6-position and the 7-position of the indeno(2,1-f)naphtho(1,2-b)pyran structure via the hetero atom like the compound represented by the following formula (18).

Подробнее
Номер записи: 45
27-02-2014 дата публикации

BENZOBISTHIAZOLE BUILDING BLOCKS FOR CONJUGATED POLYMERS

Номер: US20140058110A1
Автор: Huang Hui
Принадлежит: Phillips 66 Company

A composition having the structure comprising: 2. The composition of claim 1 , wherein the n-alkane chain has more than 3 carbons claim 1 ,3. The composition of claim 1 , wherein the n-alkane chain has 6 carbons.4. The composition of claim 1 , wherein X and Y are different elements.5. The composition of claim 1 , wherein Z is Br.6. The composition of claim 1 , wherein X is N.7. The composition of claim 1 , wherein Y is S.8. The composition of claim 1 , wherein Z is Br claim 1 , X is N and Y is S.9. The composition of claim 1 , wherein Z is Br claim 1 , X is N claim 1 , Y is S and the n-alkane chain has 6 carbons.10. The composition of claim 1 , wherein the mass spectrometry has a peak at 518.0.11. The composition of claim 1 , wherein the mass spectrometer has peaks at 55.0 claim 1 , 81.9 claim 1 , 188.9 claim 1 , 230.0 claim 1 , 250.9 claim 1 , 296.9 claim 1 , 376.8 claim 1 , 447.9 claim 1 , 474.9 claim 1 , and 518.0.13. A composition prepared by a process comprising the steps of:(a) synthesizing 2,5-dihyxylbenzene-1,4-diamine from 1,4-dibromohexyl benzene;(b) synthesizing 1,1′-(2,5-dihexyl-1,4-phenylene)bis(thiourea) from 2,5-dihyxylbenzene-1,4-diamine;(c) synthesizing 4,8-dihexylbenzo[1,2-d:4,5-d′]bis(thiazole)-2,6-diamine from 1,1-(2,5-dihexyl-1,4-phenylene)bis(thiourea); and(d) synthesizing 2,6-dibromo-4,8-dihexylbenzo[1,2-d:4,5-d′]bis(thiazole) from 4,8-dihexylbenzo[1,2-d:4,5-d′]bis(thiazole)-2,6-diamine.14. A composition prepared by a process comprising the steps of:(a) synthesizing 2,5-dihyxylbenzene-1,4-diamine from 1,4-dibromohexyl benzene;(b) synthesizing N,N′-(((2,5-dihexyl-1,4-phenylene)bis(azanediyl))bis(carbonothioyl))dibenzamide from 2,5-dihyxylbenzene-1,4-diamine;(c) synthesizing 1,1′-(2,5-dihexyl-1,4-phenylene)bis(thiourea) from N,N′-(((2,5-dihexyl-1,4-phenylene)bis(azanediyl))bis*carbonothiol))dibenzamide;(d) synthesizing 4,8-dihexylbenzo[1,2-d:4,5-d′]bis(thiazole)-2,6-diamine from 1,1′-(2,5-dihexyl-1,4-phenylene)bis(thiourea); and(e) synthesizing ...

Подробнее
Номер записи: 46
27-02-2014 дата публикации

PROCESS OF MANUFACTURING BENZOBISTHIAZOLE BUILDING BLOCKS FOR CONJUGATED POLYMERS

Номер: US20140058111A1
Автор: Huang Hui
Принадлежит: Phillips 66 Company

A process comprising the step of synthesizing 2,6-dibromo-4,8-dihexylbenzo[1, 2-d:4,5-d′]bis(thiazole) from 2,5-dihyxylbenzene-1,4-diamine. 1. A process comprising the step of:(a) synthesizing 2,6-dibromo-4,8-dihexylbenzo[1,2-d:4,5-d′]bis(thiazole) from 2,5-dihyxylbenzene-1,4-diamine.2. The process of claim 1 , wherein 2 claim 1 ,5-dihyxylbenzene-1 claim 1 ,4-diamine is synthesized from 1 claim 1 ,4-dibromohexyl benzene prior to synthesizing 2 claim 1 ,6-dibromo-4 claim 1 ,8-dihexylbenzo[1 claim 1 ,2-d:4 claim 1 , 5-d′]bis(thiazole).3. The process of claim 2 , wherein 1 claim 2 ,1′-(2 claim 2 ,5-phenylene)bis(thiourea) is synthesized from 2 claim 2 ,5-dihyxylbenzene-1 claim 2 ,4-diamine prior to synthesizing 2 claim 2 ,6-dibromo-4 claim 2 , 8-dihexylbenzo[1 claim 2 ,2-d:4 claim 2 ,5-d′]bis(thizole).4. The process of claim 3 , wherein 4 claim 3 ,8-dihexylbenzo[1 claim 3 ,2-d:4 claim 3 ,5-d′]bis(thiazole)-2 claim 3 ,6-diamine is synthesized from 1 claim 3 ,1′-(2 claim 3 ,5-dihexyl-1 claim 3 ,4-phenylene)bis(thiourea) prior to synthesizing 2 claim 3 ,6-dibromo-4 claim 3 ,8-dihexylbenzo[1 claim 3 ,2-d:4 claim 3 ,5-d′]bis(thiazole).5. The process of claim 2 , wherein N claim 2 ,N′-(((2 claim 2 ,5-dihexyl-1 claim 2 , 4-phenylene)bis(azanediyl))bis(carbonothioyl))dibenzamide is synthesized from 2 claim 2 ,5-dihyxylbenzene-1 claim 2 ,4-diamine prior to synthesizing 2 claim 2 ,6-dibromo-4 claim 2 ,8-dihexylbenzo[1 claim 2 ,2-d:4 claim 2 ,5-d′]bis(thiazole).6. The process of claim 5 , wherein 1 claim 5 ,1′-(2 claim 5 ,5-dihexyl-1 claim 5 ,4-phenylene)bis(thiourea) is synthesized from N claim 5 ,N′-(((2 claim 5 ,5-dihexyl-1 claim 5 ,4-phenylene)bis(azanediyl))bis(carbonothioyl))dibenzamide prior to synthesizing 2 claim 5 ,6-dibromo-4 claim 5 ,8-dihexylbenzo [1 claim 5 ,2-d:4 claim 5 ,5-d′]bis(thiazole).7. The process of claim 1 , wherein the 2 claim 1 ,6-dibromo-4 claim 1 ,8-dihexylbenzo[1 claim 1 ,2-d:4 claim 1 ,5-d′]bis(thiazole) is used in the synthesis of push-pull ...

Подробнее
Номер записи: 47
06-03-2014 дата публикации

FUSED HETEROCYCLIC DERIVATIVES AS S1P MODULATORS

Номер: US20140066433A1
Автор: Coolen Hein K.A.C., den Hartog Jacobus A.J., Hobson Adrian, Iwema Bakker Wouter I., Sliedregt Leonardus A.J.M., Smid Pieter, van Dongen Maria J.P.
Принадлежит:

The present invention relates to a fused heterocyclic derivative of the formula (I) The variables R1-R4, z, A, Q, X and Y are as defined in the claims. The following heterocycles are exemplified sub-structures of formula (I): The compounds of formula (I) are modulators of the S1P receptor (Sphingosine-1-phosphate receptor), More specifically, they are agonists of S1P5. The compounds have therapeutic use in treatment of cognitive disorders, age-relate cognitive decline and dementia. 2. The compound of claim 1 , wherein 'a group selected from a (3-6C)cycloalkyl group and a (8-10C)bicyclic group wherein the group is optionally substituted with a halogen atom, (1-4C)alkyl, and a phenyl group wherein the phenyl group is optionally substituted with at least one substituent independently selected from a halogen atom, cyano, (1-4C)alkyl, (1-4C)alkoxy, a trifluoromethyl, and a trifluoromethoxy;', 'R1 is selected from'}{'sub': '2', 'W is selected from a bond, —O—, —CO—, —S—, —SO—, —SO—, —NH—, —CH═CH—, —C≡C—, and a trans-cyclopropylene; and'}n is an integer from 0 to 4; andR2 is selected from H and at least one substituent independently selected from a halogen atom, (1-4C)alkyl optionally substituted with at least one fluoro, and (1-4C)alkoxy optionally substituted with at least one fluoro atom.5. The compound of claim 1 , wherein Y is O.6. The compound of claim 1 , wherein R4 is selected from —(CH)—COOH claim 1 , —(CH)—COOH claim 1 , —CH—CHCH—COOH claim 1 , —CH—C(CH)—COOH claim 1 , —CHCH—CH—COOH claim 1 , —CH—CF—COOH claim 1 , and 1 claim 1 ,3-cyclobutylene-COOH.7. The compound of claim 1 , wherein R1 is a phenyl group optionally substituted with at least one substituent independently selected from halogen claim 1 , cyano claim 1 , (1-4C)alkyl optionally substituted with at least one halogen atom claim 1 , (1-4C)alkoxy optionally substituted with at least one halogen atom claim 1 , amino claim 1 , dimethylamino claim 1 , and (3-6C)cycloalkyl optionally substituted with a ...

Подробнее
Номер записи: 48
06-03-2014 дата публикации

Inhibitors of Memapsin 2 Cleavage for the Treatment of Alzheimer's Disease

Номер: US20140066488A1
Автор: Ghosh Arun K., Kalapala Venkateswararao, Tang Jordan
Принадлежит:

Proteases such as memapsin 2 are important enzymes, playing roles in a variety of diseases including Alzheimer's Disease. The inventors have developed inhibitors of memapsin 2 and methods of use therefore in the treatment of disease. 210-. (canceled)1220-. (canceled)21. The method of claim 11 , wherein said subject is further treated with at least a second Alzheimer's Disease therapy.22. (canceled)23. The method of claim 11 , wherein treating comprises one or more of improvements in memory claim 11 , cognition or learning claim 11 , slowing the progression of symptoms or pathophysiology claim 11 , improving quality of life claim 11 , or increasing life span.24. The method of claim 11 , wherein said compound is administered orally or by injection claim 11 , including intravenously claim 11 , intradermally claim 11 , intraarterially claim 11 , intraperitoneally claim 11 , intracranially claim 11 , intraarticularly claim 11 , intraprostaticaly claim 11 , intrapleurally claim 11 , intramuscularly claim 11 , or subcutaneously.25. (canceled)26. The method of claim 11 , further comprising measuring cognition or memory in said subject prior to and/or after administration of said compound.27. The method of claim 11 , wherein said mammalian subject is a human.29. The compound of claim 28 , wherein the compound has formula I claim 28 , wherein X is H and Y is OH.30. The compound of claim 28 , wherein the compound has formula I claim 28 , wherein X is H and Y is H.31. The compound of claim 28 , wherein the compound has formula II claim 28 , wherein R is H claim 28 , R′ is —CH claim 28 , and R″ is isobutyl.32. The compound of claim 28 , wherein the compound has formula II claim 28 , wherein R is H claim 28 , R′ is n-propyl claim 28 , and R″ is isobutyl.33. The compound of claim 28 , wherein the compound has formula II claim 28 , wherein R is H claim 28 , R′ is isopropyl claim 28 , and R″ is isobutyl.34. The compound of claim 28 , wherein the compound has formula II claim 28 , ...

Подробнее
Номер записи: 49
20-03-2014 дата публикации

TETRAHYDROTHIAZEPINE DERIVATIVE

Номер: US20140080808A1
Автор: AOYAGI Atsushi, BABA Takayuki, FUJII Kunihiko, INUI Masaharu, MORI Makoto, Onishi Yukari
Принадлежит: Daiichi Sankyo Company, Limited

The present invention relates to a compound represented by the following general formula (I) 3. The compound or a pharmacologically acceptable salt thereof according to claim 1 , wherein Rrepresents a heterocyclic group that may be substituted with 1 to 4 group(s) independently selected from substituent group A.4. The compound or a pharmacologically acceptable salt thereof according to claim 1 , wherein Rrepresents a pyridyl group claim 1 , a pyrimidinyl group claim 1 , or a pyrazolyl group that may be substituted with one group selected from substituent group A.5. The compound or a pharmacologically acceptable salt thereof according to claim 1 , wherein substituent group A represents C-Calkyl groups or groups represented by the formula —C(═O)—NRR(Rand Rare identical to or different from each other and each independently represents a hydrogen atom claim 1 , a C-Calkyl group claim 1 , or a C-Ccycloalkyl group claim 1 , or Rand Rform a 4 to 6-membered saturated heterocyclic ring together with the nitrogen atom bound therewith claim 1 , wherein the 4 to 6-membered saturated heterocyclic ring may further contain one oxygen atom).6. The compound or a pharmacologically acceptable salt thereof according to claim 1 , wherein n represents 0.7. A compound selected from the group consisting of:[3-(1-biphenyl-4-ylcyclopropyl)-8-methyl-5,6,8,9-tetrahydro[1,2,4]triazolo[4,3-d][1,4]thiazepin-8-yl]methanol,{8-methyl-3-[1-(4-pyridin-3-ylphenyl)cyclopropyl]-5,6,8,9-tetrahydro [1,2,4]triazolo[4,3-d][1,4]thiazepin-8-yl}methanol,{(8S)-8-methyl-3-[1-(4-pyridin-3-ylphenyl)cyclopropyl]-5,6,8,9-tetrahydro [1,2,4]triazolo[4,3-d][1,4]thiazepin-8-yl}methanol,{(8R)-8-methyl-3-[1-(4-pyridin-3-ylphenyl)cyclopropyl]-5,6,8,9-tetrahydro [1,2,4]triazolo[4,3-d][1,4]thiazepin-8-yl}methanol,4′-{1-[8-(hydroxymethyl)-8-methyl-5,6,8,9-tetrahydro[1,2,4]triazolo[4,3-d][1,4]thiazepin-3-yl]cyclopropyl}-N,N-dimethylbiphenyl-4-carboxamide,4′-{1-[8-(hydroxymethyl)-8-methyl-5,6,8,9-tetrahydro [1,2,4]triazolo[4,3-d ...

Подробнее
Номер записи: 50
20-03-2014 дата публикации

HETEROCYCLIC COMPOUND AND USE THEREOF

Номер: US20140080817A1
Автор: ASANO Yasutomi, Honda Eiji, IMAEDA Toshihiro, KORI Masakuni, Mochizuki Michiyo, Nakamura Shinji, TOYOFUKU Masashi, Ujikawa Osamu
Принадлежит: Takeda Pharmaceutical Company Limited

Provided is a compound represented by the formula (I): 113-. (canceled)24. 9-[4-(4-Methylphenoxy)phenyl]-3 ,4-dihydropyrido[2 ,1-c][1 ,2 ,4]thiadiazine 2 ,2-dioxide or a pharmaceutically acceptable salt thereof.25. A medicament comprising 9-[4-(4-methylphenoxy)phenyl]-3 ,4-dihydropyrido[2 ,1-c][1 ,2 ,4]thiadiazine 2 ,2-dioxide or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier. The present invention relates to a heterocyclic compound, particularly a heterocyclic compound having an AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) receptor potentiating action.Glutamate is the most abundant excitatory neurotransmitter in the mammalian central nervous system. Glutamate plays a pivotal role in cognition, mood, and motor function, and its neurotransmission becomes unstable in psychiatric diseases and neurological disorder. Glutamate receptors are divided into ligand gated ion channels and G protein-coupled receptors, and the ligand gated ion channels are further divided into α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors, N-methyl-D-aspartic acid (NMDA) receptors, and kainic acid (KA) receptors. (non-patent document 1)AMPA receptor is one kind of receptor for excitatory neurotransmitter glutamate, and was named for the selective activation of the receptor by AMPA. AMPA receptors are composed of 4 subunits (GluR1, GluR2, GluR3, GluR4). Each subunit exists in flip and flop alternatively spliced variants. AMPA receptors form homo- or hetero-tetramers composed of these subunits in vivo. The physiological property of AMPA receptor has been reported to change depending on the subunit composition. (non-patent documents 1, 2, 3)The importance of AMPA receptor in cerebrophysiology is well known, and a compound having an AMPA receptor potentiating action is expected to be useful as a prophylactic or therapeutic drug for psychiatric diseases, neurodegenerative diseases, cognitive disorders, sleep disorders and ...

Подробнее
Номер записи: 51
27-03-2014 дата публикации

QUINOLONE ANALOGS FOR TREATING AUTOIMMUNE DISEASES

Номер: US20140086839A1
Автор: Achiron Anat, Gurevich Michael
Принадлежит: TEL HASHOMER MEDICAL RESEARCH INFRASTRUCTURE AND SERVICES LTD.

Provided are methods of treating autoimmune diseases by administering to the subject a therapeutically effective amount of a quinolone compound such as 2-(4-methyl-1,4-diazepan-1-yl)-N-((5-methylpyrazin-2-yl)methyl)-5-oxo-5H-benzo[4,5]thiazolo[3,2-a][1,8]naphthyridine-6-carboxamide (CX-5461). Also provided are methods of monitoring efficiency of treatment of the quinolone compound by determining the expression level of at least one gene of the RNA polymerase I pathway. 49-. (canceled)10. A method of monitoring treatment efficiency of a subject having an autoimmune disease , the method comprising:{'claim-ref': {'@idref': 'CLM-00001', 'claim 1'}, '(a) treating the subject with said compound according to the method of , and'}(b) comparing a level of expression of least one gene involved in the RNA polymerase I pathway in a cell of the subject following said treating with said compound to a level of expression of said at least one gene in a cell of the subject prior to said treating the subject with said compound,(i) wherein a decrease above a predetermined threshold in said level of expression of said at least one gene following said treating with said compound relative to said level of expression of said at least one gene prior to said treating with said compound indicates that said compound is efficient for treating the subject;(ii) wherein an increase above a predetermined threshold in said level of expression of said at least one gene following said treating with said compound relative to said level of expression of said at least one gene prior to said treating with said compound indicates that said compound is not efficient for treating the subject; or(iii) wherein when a level of expression of said at least one gene following said treating with said compound is identical or changed below a predetermined threshold as compared to prior to said treating with said compound then the treatment is not efficient for treating the subjectthereby monitoring treatment ...

Подробнее
Номер записи: 52
27-03-2014 дата публикации

6,7-DIHYDRO-[1,3,4]THIADIAZOLO-[3,2-a][1,3]DIAZEPIN DERIVATIVE AND PHARMACEUTICAL COMPOSITION CONTAINING THE SAME AS NEUROMUSCULAR BLOCKER OR SKELETAL MUSCLE RELAXANT, AND METHOD FOR THE PREPARATION

Номер: US20140088091A1
Автор: Abdelaziz Alaa A.-M., Al-Omar Mohamed A., Al-Omary Fatmah A., Al-Rashood Khalid A., El-Azab Adel S., El-Subbagh Hussein I., El-Taher Kamal E. H., Hassan Ghada S., Hefnawy Mohamed M.
Принадлежит: KING SAUD UNIVERSITY

The present invention relates to a compound of formula 1, a pharmaceutical composition containing the compound, a method for its preparation as well as the use of the compound as neuromuscular blocker or skeletal muscle relaxant. 2. The compound according to claim 1 , wherein Ris hydrogen claim 1 , mercapto or C-C-alkyl.3. The compound according to claim 2 , wherein Ris hydrogen or is taken together with Rto form an alicyclic claim 2 , aryl or heteroaryl ring system claim 2 , which is optionally substituted by halogen claim 2 , amino claim 2 , C-C-alkyl claim 2 , C-C-haloalkyl claim 2 , C-C-alkoxy claim 2 , C-C-haloalkoxy claim 2 , mercapto claim 2 , alkylthio claim 2 , alkylamino claim 2 , arylthio claim 2 , heteroarylthio claim 2 , arylamino or heteroarylamino.4. The compound according to claim 1 , wherein R claim 1 , R claim 1 , Rand Rare independently selected from aryl or heteroaryl.5. The compound according to claim 4 , wherein the compound is an addition salt of hydrochloride claim 4 , hydrobromide claim 4 , phosphate claim 4 , nitrate claim 4 , acetate claim 4 , malate claim 4 , succinate claim 4 , fumarate claim 4 , tartrate claim 4 , salicylate claim 4 , sorbate claim 4 , lactate claim 4 , p-toluene sulphate claim 4 , or naphthalene-1 claim 4 ,5-disulfonate.7. The method according to claim 6 , wherein the reaction of compound 2 and compound 3 is in the presence of a solvent.8. The method according to claim 7 , wherein the reaction of compound 4 is a cyclization reaction with diethyl amine claim 7 , pyrrolidine claim 7 , morpholine claim 7 , piperidine claim 7 , N-methylpiperazine claim 7 , in toluene claim 7 , ethylbenzane claim 7 , o-xylene claim 7 , m-xylene claim 7 , p-xylene claim 7 , or isopropylbenzene.9. A pharmaceutical composition comprising a compound according to and a pharmaceutically acceptable carrier or excipient.10. Use of the compound of as a neuromuscular blocker or skeletal muscle relaxant.11. The compound of claim 3 , wherein the ...

Подробнее
Номер записи: 53
03-04-2014 дата публикации

Method for Preparing Largazole Analogs and Uses Thereof

Номер: US20140093449A1
Автор: Bowers Albert, Bradner James E., Newkirk Tenaya, Wiest Olaf G., Williams Robert M.
Принадлежит:

Analogs of largazole are described herein. Methods of treating cancer and blood disorders using largazole and largazole analogs and pharmaceutical compositions comprising the same are additionally described herein. Methods for preparing largazole analogs are likewise described. 23-. (canceled)58-. (canceled)1021-. (canceled)22. A method for treating cancer in a subject , comprising administering to the subject a combination of: i) a therapeutically effective amount of the compound of or a pharmaceutical composition comprising a compound of ; and ii) an antibody against a tumor-associated antigen.2327-. (canceled)28. The method of claim 22 , further comprising obtaining the compound.29. The method of claim 22 , wherein the subject is human.30. A pharmaceutical composition comprising a therapeutically effective amount of the compound of and at least one pharmaceutically acceptable excipient for treating cancer in a subject.3133-. (canceled)34. The pharmaceutical composition of claim 30 , wherein the subject is human.35. (canceled)36. The compound of claim 1 , wherein Ris H or lower alkyl.37. The compound of claim 1 , wherein Ris methyl.38. The compound of claim 1 , wherein Ris lower alkyl.39. The compound of claim 1 , wherein Ris isopropyl.40. The compound of claim 1 , wherein X is S.41. The compound of claim 1 , wherein Z is S.42. The method of claim 22 , wherein the antibody is a naked antibody claim 22 , an immunotoxin claim 22 , or a radioconjugate.43. The method of claim 22 , wherein Y is NH.44. The method of claim 22 , wherein X is S.45. The method of claim 22 , wherein Z is S.46. The method of claim 22 , wherein the compound is a prodrug of the compound of Formula (I).47. A method for preparing the macrocycle compound of claim 1 , said method comprising:i) providing four building blocks or subunits of the macrocycle compound of Formula I;ii) coupling the building blocks or subunits of the macrocycle compound of Formula I by sequentially installing the ester or ...

Подробнее
Номер записи: 54
03-04-2014 дата публикации

TETRAHYDROPYRROLOTHIAZINE COMPOUNDS

Номер: US20140094454A1
Автор: BECK James Peter, GREEN Steven James, JR. Leonard Larry, LOPEZ Jose Eduardo, MATHES Brian Michael, MERGOTT Dustin James, PORTER Warren Jaye, RANKOVIC Zoran, SHI Yuan, WATSON Brian Morgan, WINNEROSKI
Принадлежит: ELI LILLY AND COMPANY

The present invention provides compounds of Formula I: 118-. (canceled)22. A pharmaceutical composition according to wherein Ris F.23. A pharmaceutical composition according to wherein Ris H.25. A pharmaceutical composition according to wherein Ris H.26. A pharmaceutical composition according to wherein Ris H. The present invention relates to novel tetrahydropyrrolothiazine compounds, to pharmaceutical compositions comprising the compounds, to methods of using the compounds to treat physiological disorders, and to intermediates and processes useful in the synthesis of the compounds.The present invention is in the field of treatment of Alzheimer's disease and other diseases and disorders involving amyloid β (Aβ) peptide, a neurotoxic and highly aggregatory peptide segment of the amyloid precursor protein (APP). Alzheimer's disease is a devastating neurodegenerative disorder that affects millions of patients worldwide. In view of the currently approved agents on the market which afford only transient, symptomatic benefits to the patient, there is a significant unmet need in the treatment of Alzheimer's disease.Alzheimer's disease is characterized by the generation, aggregation, and deposition of Aβ in the brain. Complete or partial inhibition of β-secretase βi-site amyloid precursor protein-cleaving enzyme; BACE) has been shown to have a significant effect on plaque-related and plaque-dependent pathologies in mouse models suggesting that even small reductions in Aβ peptide levels might result in a long-term significant reduction in plaque burden and synaptic deficits, thus providing significant therapeutic benefits, particularly in the treatment of Alzheimer's disease.US 2009/0209755 discloses fused aminodihydrothiazine derivatives which possess BACE inhibitory activity and are further disclosed as useful therapeutic agents for a neurodegenerative disease caused by Aβ peptide, such as Alzheimer's type dementia. In addition, 31(46), pages 16507-16516 (2011) discloses ( ...

Подробнее
Номер записи: 55
06-01-2022 дата публикации

FGFR4 INHIBITOR AND USE THEREOF

Номер: US20220002307A1
Автор: Ding Lieming, GAO Jinheng, LIU Xiangyong, SUN Zhongxin, Wang Jiabing, XU Xiaofeng, Zhang Yun
Принадлежит:

Disclosed is a compound as a fibroblast growth factor receptor 4 (FGFR4) inhibitor (as shown in formula (I)), and a pharmaceutical composition thereof and a preparation method therefor, as well as the use of same in the treatment of FGFR4-mediated diseases. The above-mentioned compounds act by participating in a number of processes, such as regulating cell proliferation, apoptosis, migration, neovascularization. 2. The compound or a pharmaceutically acceptable salt claim 1 , solvate claim 1 , chelate claim 1 , non-covalent complex claim 1 , or prodrug thereof of claim 1 , wherein L claim 1 , Q and T is selected from the following groups:{'sub': '2', '(i) L is C, Q is N, T is CH;'}(ii) L is C, Q is N, T is C;(iii) L is C, Q is C, T is N;(iv) L is C, Q is N, T is CH;{'sub': '2', '(v) L is N, Q is N, T is CH; or'}(vi) L is C, Q is CH, T is O.4. The compound or a pharmaceutically acceptable salt claim 1 , solvate claim 1 , chelate claim 1 , non-covalent complex claim 1 , or prodrug thereof of claim 1 , wherein ring A is phenyl claim 1 , Cheteroaryl or Cheterocyclyl claim 1 , wherein the Cheteroaryl optionally containing 1 claim 1 , 2 or 3 heteroatoms selected from N and S claim 1 , the Cheterocyclyl is a fused bicyclic which has two N atoms and one O atom in the ring.5. The compound or a pharmaceutically acceptable salt claim 1 , solvate claim 1 , chelate claim 1 , non-covalent complex claim 1 , or prodrug thereof of claim 1 , wherein ring A is Cheteroaryl.6. The compound or a pharmaceutically acceptable salt claim 1 , solvate claim 1 , chelate claim 1 , non-covalent complex claim 1 , or prodrug thereof of claim 1 , wherein Ris selected from the group consisting of H claim 1 , halogen claim 1 , cyano claim 1 , Calkyl claim 1 , halogen substituted Calkyl claim 1 , —(CH)NRRsubstituted amino claim 1 , Calkoxy which substituted with substituted Cheterocyclyl claim 1 , wherein Rand Rare each optionally selected from Calkyl.8. The compound or a pharmaceutically acceptable ...

Подробнее
Номер записи: 56
06-01-2022 дата публикации

PROCESS FOR THE PREPARATION OF CYCLIC DEPSIPEPTIDES

Номер: US20220002347A1
Автор: Fu Xiaoyong, Li Zhifeng, Liu Huayan, Piscopio Anthony D., Shi Feng
Принадлежит: OnKure, Inc.

Processes for preparing compounds of Formula (1) and Formula (2) are described, wherein X, Y, Z, R-R, L and n are defined herein. Intermediates useful in the preparation of the compounds of Formula (1) and Formula (2) are also described. 117.-. (canceled)19. The alkyl chloride compound according to claim 18 ,{'sub': 1', '2', '4', '5', '6', '1', '10, 'wherein R, R, Ra, R, Rand Rare independently H or C-Calkyl.'}20. The alkyl chloride compound according to claim 18 ,wherein:{'sub': 1', '2, 'Rand Rare H;'}{'sub': 3', '4', '1', '10, 'Rand Rare independently C-Calkyl; and'}{'sub': 5', '6', '1', '10', '5', '1', '10', '6, 'Ris H and Ris C-Calkyl, or Ris C-Calkyl and Ris H.'}21. The alkyl chloride compound according to claim 18 ,wherein:{'sub': 1', '2, 'Rand Rare H;'}{'sub': 3', '4', '3, 'Rand Rare CH; and'}{'sub': 5', '6', '5', '6, 'Ris H and Ris isopropyl, or Ris isopropyl and Ris H.'}24. The method according to claim 23 , wherein for the compound of Formula (XXV) or a pharmaceutically acceptable salt thereof claim 23 ,{'sub': 1', '2, 'Rand Rare H;'}{'sub': 3', '4', '1', '10, 'Rand Rare independently C-Calkyl; and'}{'sub': 5', '6', '1', '10', '5', '1', '10', '6, 'Ris H and Ris C-Calkyl, or Ris C-Calkyl and Ris H.'}25. The method according to claim 23 , wherein for the compound of Formula (XXV) or a pharmaceutically acceptable salt thereof claim 23 ,{'sub': 1', '2, 'Rand Rare H;'}{'sub': 3', '4', '3, 'Rand Rare CH; and'}{'sub': 5', '5', '6, 'Ris H and R is isopropyl, or Ris isopropyl and Ris H.'}27. The method according to claim 26 , wherein the pharmaceutically acceptable salt is a hydrochloride salt.28. The method according to claim 26 , wherein the pharmaceutically acceptable salt is a sulfonate salt.29. The method according to claim 28 , wherein the sulfonate salt is a benzenesulfonate salt. The invention relates to the preparation of substituted, cyclic depsipeptides and to intermediates useful in their preparation. The cyclic depsipeptides prepared as described ...

Подробнее
Номер записи: 57
07-01-2016 дата публикации

Carbocyclic- And Heterocyclic-Substituted Hexahydropyrano[3,4-d][1,3]Thiazin-2-Amine Compounds

Номер: US20160002264A1
Автор: "ONeill Brian Thomas", Brodney Michael Aaron, BUTLER CHRISTOPHER RYAN, LaChapelle Erik Alphie
Принадлежит: PFIZER INC.

The present invention provides compounds of formula I, 2. The compound of claim 1 , or a tautomer thereof or a pharmaceutically acceptable salt of said compound or tautomer claim 1 , wherein Ris —(C(R)(R))—(C-C)cycloalkyl; wherein said (C-C)cycloalkyl moiety is optionally substituted with one to three R; Rat each occurrence is independently fluoro or methyl claim 1 , wherein said methyl moiety is optionally substituted with one to three fluoro; Rat each occurrence is independently fluoro or methyl claim 1 , wherein said methyl moiety is optionally substituted with one to three fluoro; m is 0 or 1; and b is 0 claim 1 , 1 claim 1 , 2 claim 1 , or 3.3. The compound of claim 2 , or a tautomer thereof or a pharmaceutically acceptable salt of said compound or tautomer claim 2 , wherein Ris cyclopropyl.4. The compound of claim 3 , or a tautomer thereof or a pharmaceutically acceptable salt of said compound or tautomer claim 3 , wherein said compound is selected from the group consisting of:(4aR,6R,8aS)-6-Cyclopropyl-8a-(2,4-difluorophenyl)-4,4a,5,6,8,8a-hexahydropyrano[3,4-d][1,3]thiazin-2-amine;(4R,4aR,6R,8aS)-6-Cyclopropyl-8a-(2,4-difluorophenyl)-4-methyl-4,4a,5,6,8,8a-hexahydropyrano[3,4-d][1,3]thiazin-2-amine;rel-(4S,4aR,6R,8aS)-6-Cyclopropyl-8a-(2,4-difluorophenyl)-4-(methoxymethyl)-4,4a,5,6,8,8a-hexahydropyrano[3,4-d][1,3]thiazin-2-amine;(4S,4aR,6R,8aS)-6-Cyclopropyl-8a-(2,4-difluorophenyl)-4-(fluoromethyl)-4,4a,5,6,8,8a-hexahydropyrano[3,4-d][1,3]thiazin-2-amine;(4aR,6R,8aS)-8a-(2,4-Difluorophenyl)-6-(1-methylcyclopropyl)-4,4a,5,6,8,8a-hexahydropyrano[3,4-d][1,3]thiazin-2-amine;(4aR,6R,8aS)-6-Cyclopropyl-8a-(2,4,6-trifluorophenyl)-4,4a,5,6,8,8a-hexahydropyrano[3,4-d][1,3]thiazin-2-amine;(4aR,6R,8aS)-6-Cyclopropyl-8a-(4-fluorophenyl)-4,4a,5,6,8,8a-hexahydropyrano[3,4-d][1,3]thiazin-2-amine;(4aR,6R,8aS)-6-Cyclopropyl-8a-(2,5-difluorophenyl)-4,4a,5,6,8,8a-hexahydropyrano[3,4-d][1,3]thiazin-2-amine;(4aR,6R,8aS)-6-Cyclopropyl-8a-(2,6-difluorophenyl)-4,4a,5,6,8,8a- ...

Подробнее
Номер записи: 58
07-01-2016 дата публикации

MACROCYCLIC COMPOUNDS AS IRAK4 INHIBITORS FOR THE TREATMENT OF INFLAMMATORY DISEASES

Номер: US20160002265A1
Автор: Jenkins Tracy, Vessels Jeffery
Принадлежит: Biogen MA Inc.

Provided are compounds of Formula (I), or pharmaceutically acceptable salts thereof, wherein i.a. Ring A is phenylene or 5- to 6-membered heteroarylene; Ring B is phenylene, 5- to 6-membered heterocycloalkylene or 5- to 6-membered heteroarylen; Ris absent, heteroarylene, arylene, C1-3 alkylene, or Rand Rtaken together with the nitrogen to which they are bound form a 3- to 7-membered heterocycloalkyl ring; Ris absent, C(0)NR, NRor 0; Ris C2-10 alkylene or alkenylene, wherein one or two of the carbon atoms in the alkylene chain is optionally replaced by an 0, S, SO, SOor NR, and wherein two of the carbon atoms in the alkylene chain are optionally connected by a two or three carbon atom alkylene chain to form a 5- to 7-membered ring; Ris absent, NRor O. The compounds are IRAK4 inhibitors useful for the treatment of inflammatory diseases. 3. The compound of claim 2 , or a pharmaceutically acceptable salt thereof claim 2 , wherein ring A is chosen from phenylene claim 2 , pyridinediyl claim 2 , pyridazinediyl claim 2 , pyrimidinediyl claim 2 , pyrazinediyl claim 2 , triazinediyl claim 2 , imidazolediyl claim 2 , oxazolediyl claim 2 , thiazolediyl claim 2 , pyrazolediyl claim 2 , isoxazolediyl claim 2 , and isothiazolediyl claim 2 , wherein ring A is optionally substituted with lower alkyl that is further optionally substituted with hydroxyl claim 2 , alkoxy claim 2 , amino claim 2 , N-(alkyl)amino claim 2 , N claim 2 ,N-(dialkyl)amino claim 2 , or halogen.710.-. (canceled)12. (canceled)13. The compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 ,{'sup': 4', '41', '41, 'claim-text': heterocycloalkyl,', {'sup': 9', '10', '11, 'lower alkyl optionally substituted with —C(O)OR, —C(O)NRR, hydroxy, amino, N-(alkyl)amino, N,N-(dialkyl)amino, cycloalkyl, or heterocycloalkyl,'}, {'sup': '9', '—C(O)OR,'}, 'hydroxyl, and', {'sup': 10', '11, '—C(O)NRR,'}, {'sup': '9', 'wherein Ris chosen from hydrogen and lower alkyl,'}, {'sup': 10', '11', '10', '11, 'wherein ...

Подробнее
Номер записи: 59
03-01-2019 дата публикации

BACE1 INHIBITORS

Номер: US20190002476A1
Автор: Bartels Bjoern, Dolente Cosimo, Guba Wolfgang, Haap Wolfgang, Obst Sander Ulrike, Vifian Walter, Woltering Thomas
Принадлежит:

The present invention provides a compound of formula I, having BACE1 inhibitory activity, their manufacture, pharmaceutical compositions containing them and their use as therapeutically active substances. The active compounds of the present invention are useful in the therapeutic and/or prophylactic treatment of e.g. Alzheimer's disease. 2. The compound according to claim 1 , wherein n claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , Rand Rare as described and when n=1 claim 1 , then the 5-ring has cis configuration.4. The compound according to claim 1 , wherein Rand Rare methyl.5. The compound according to claim 1 , wherein Rand Rare hydrogen.6. The compound according to claim 1 , wherein Ris hydrogen.7. The compound according to claim 1 , wherein Ris methyl.8. The compound according to claim 1 , wherein Ris F.9. The compound according to claim 1 , wherein Ris heteroaryl claim 1 , substituted by 1-2 substituents individually selected from cyano claim 1 , halogen claim 1 , halogen-C-alkoxy claim 1 , halogen-C-alkyl and C-alkyl.10. The compound according to claim 1 , wherein Ris heteroaryl which is selected from pyridinyl claim 1 , pyrazinyl claim 1 , pyrimidyl or 1H-pyrazolyl claim 1 , each substituted by 1-2 substituents individually selected from cyano claim 1 , halogen claim 1 , halogen-C-alkoxy claim 1 , halogen-C-alkyl and C-alkyl.11. The compound according to claim 1 , wherein Ris heteroaryl claim 1 , substituted by 1-2 substituents individually selected from cyano and C-alkyl.12. The compound according to claim 1 , wherein Ris phenyl substituted by 1-2 substituents individually selected from cyano claim 1 , halogen and C-alkyl.13. The compound according to claim 1 , wherein n is 1.14. The compound according to claim 1 , selected from the group consisting of:N-(3-((3aR,4R,8S)-6-amino-4,7,7-trimethyl-8-oxido-3,3a,4,7-tetrahydro-2H-isothiazolo[1,5-a][1,4]thiazin-4-yl)-4-fluorophenyl)-5-cyano-3-methylpicolinamide,N-(3-((3aS,4R,8R ...

Подробнее
Номер записи: 60
02-01-2020 дата публикации

MACROCYCLIC COMPOUNDS FOR TREATMENT OF MEDICAL DISORDERS

Номер: US20200002347A1
Автор: Agarwal Atul, Barrish Joel Charles, Chen Dawei, EASTMAN Kyle J., Gadhachanda Venkat Rao, Phadke Avinash S., Wiles Jason Allan
Принадлежит: ACHILLION PHARMACEUTICALS, INC.

Macrocyclic Complement Factor D inhibitors, pharmaceutical compositions, and uses thereof, as well as processes for their manufacture are provided. The compounds provided include Formula I, Formula II, Formula III, Formula IV, Formula V, Formula VI, Formula VII, and Formula VIII or a pharmaceutically acceptable salt, prodrug, isotopic analog, N-oxide, or isolated isomer thereof, optionally in a pharmaceutically acceptable composition. The inhibitors described herein target Factor D and inhibit or regulate the complement cascade. 5. The compound of claim 1 , wherein B2 is a six membered heteroaryl substituted with 1 or 2 groups selected from R.6. A pharmaceutical composition comprising a compound of or a pharmaceutically acceptable salt thereof claim 1 , and a pharmaceutically acceptable carrier.11. The compound of claim 7 , wherein B1 is a six membered heteroaryl substituted with 1 claim 7 , 2 claim 7 , or 3 groups selected from R.12. A pharmaceutical composition comprising a compound of or a pharmaceutically acceptable salt thereof claim 7 , and a pharmaceutically acceptable carrier.18. The compound of claim 14 , wherein B2 is a six membered heteroaryl substituted with 1 or 2 groups selected from R.19. A pharmaceutical composition comprising a compound of or a pharmaceutically acceptable salt thereof claim 14 , and a pharmaceutically acceptable carrier.24. The compound of claim 20 , wherein B1 is a six membered heteroaryl substituted with 1 claim 20 , 2 claim 20 , or 3 groups selected from R.25. A pharmaceutical composition comprising a compound of or a pharmaceutically acceptable salt thereof claim 20 , and a pharmaceutically acceptable carrier. This application is a continuation of International Application No. PCT/US2018/020531, which claims the benefit of U.S. Application No. 62/465,600 filed Mar. 1, 2017; U.S. Application No. 62/466,252 filed Mar. 2, 2017; and U.S. Application No. 62/500,287 filed May 2, 2017. The entirety of these applications is hereby ...

Подробнее
Номер записи: 61
02-01-2020 дата публикации

POLYMORPHIC MIXTURE OF RIFAXIMIN AND ITS USE FOR THE PREPARATION OF SOLID FORMULATIONS

Номер: US20200002356A1
Автор: Argese Maria, Fumagalli Emanuela, Grilli Maria Donata, Grisenti Paride, Motta Giuseppe, Pengo Daniele
Принадлежит:

A Rifaximin polymorphic mixture of α/β form in a relative ratio of 85/15±3 and a process for its preparation. The polymorphic mixture of Rifaximin is for use as a medicament, in particular in the treatment of traveler's diarrhea and hepatic encephalopathy. A pharmaceutical composition comprises the polymorphic mixture of Rifaximin as active ingredient, in particular, a solid formulation, more in particular, a film coated tablet. A polymorphic form of crude wet rifaximin and of purified wet rifaximin their use are used as intermediates in a process for the preparation of Rifaximin polymorphic mixture of α/β form in a relative ratio of 85/15±3. 113-. (canceled)14. A method of treating a subject suffering from traveler's diarrhea comprising:selecting a subject in need of treatment of traveler's diarrhea;administering to said subject a pharmaceutical composition comprising a therapeutically effective amount of Rifaximin in an α/β polymorphic mixture of 85/15±3 in an amount sufficient to treat the traveler's diarrhea, wherein the Rifaximin α/β polymorphic mixture is characterized by an X-Ray spectrum with characteristic 2theta values at: 5.32, 5.78, 6.50, 7.24, 7.82, 8.80, 10.50, 11.02, 11.58, 13.08, 14.42, 17.32, 17.68, 18.58, 19.52, 21.04, 21.60, and 21.92.15. The method of claim 14 , wherein the pharmaceutical composition is a solid pharmaceutical composition.16. The method of claim 15 , wherein the pharmaceutical composition is a film coated tablet.17. The method of claim 14 , wherein the pharmaceutical composition comprises 550 mg of Rifaximin α/β polymorphic mixture of 85/15±3.18. The method of claim 14 , wherein the pharmaceutical composition further comprises excipients.19. The method of claim 18 , wherein the excipients comprise cellulose microcrystalline claim 18 , sodium starch glycolate claim 18 , glyceryl palmitostearate claim 18 , hydrated silicon dioxide claim 18 , and talc.20. The method of claim 19 , wherein the pharmaceutical composition further ...

Подробнее
Номер записи: 62
02-01-2020 дата публикации

POLYMORPHIC MIXTURE OF RIFAXIMIN AND ITS USE FOR THE PREPARATION OF SOLID FORMULATIONS

Номер: US20200002357A1
Автор: Argese Maria, Fumagalli Emanuela, Grilli Maria Donata, Grisenti Paride, Motta Giuseppe, Pengo Daniele
Принадлежит:

A Rifaximin polymorphic mixture of α/β form in a relative ratio of 85/15±3 and a process for its preparation. The polymorphic mixture of Rifaximin is for use as a medicament, in particular in the treatment of traveler's diarrhea and hepatic encephalopathy. A pharmaceutical composition comprises the polymorphic mixture of Rifaximin as active ingredient, in particular, a solid formulation, more in particular, a film coated tablet. A polymorphic form of crude wet rifaximin and of purified wet rifaximin their use are used as intermediates in a process for the preparation of Rifaximin polymorphic mixture of α/β form in a relative ratio of 85/15±3. 113-. (canceled)14. A Rifaximin polymorphic mixture of α/β form in a relative ratio of 85/15±3 , characterized by an X-Ray spectrum with characteristic 2theta values at: 5.32 , 5.78 , 6.50 , 7.24 , 7.82 , 8.80 , 10.50 , 11.02 , 11.58 , 13.08 , 14.42 , 17.32 , 17.68 , 18.58 , 19.52 , 21.04 , 21.60 , and 21.92.15. A pharmaceutical composition comprising the polymorphic mixture of Rifaximin of claim 14 , and a vehicle claim 14 , excipient claim 14 , or formulative ingredient.16. The pharmaceutical composition of claim 15 , wherein the pharmaceutical composition is a solid pharmaceutical composition.17. The pharmaceutical composition of claim 16 , wherein the pharmaceutical composition is a film coated tablet.18. The pharmaceutical composition of claim 15 , wherein the pharmaceutical composition comprises 550 mg of Rifaximin α/β polymorphic mixture of 85/15±3.19. The pharmaceutical composition of claim 15 , wherein the pharmaceutical composition further comprises excipients.20. The pharmaceutical composition of claim 19 , wherein the excipients comprise cellulose microcrystalline claim 19 , sodium starch glycolate claim 19 , glyceryl palmitostearate claim 19 , hydrated silicon dioxide claim 19 , and talc.21. The pharmaceutical composition of claim 20 , wherein the pharmaceutical composition further comprises polyvinyl alcohol claim ...

Подробнее
Номер записи: 63
04-01-2018 дата публикации

PHENOTHIAZINE-PYRIDINE COMPOUNDS AND USES THEREOF

Номер: US20180002348A1
Автор: Lee Hungkay, Leung Wing Nang, Wang Pan, Xiao Qicai, Xu Chuanshan
Принадлежит:

The present invention provides a novel phenothiazine-pyridine compound that is an effective photosensitizer useful for photodynamic therapy. Also provided is a method for inhibiting cell proliferation or for treating a disease involving inappropriate cell proliferation. 2. The compound according to claim 1 , wherein Ris H claim 1 , C-Calkyl claim 1 , C-Calkyl claim 1 , C-Calkoxy or C-Ccycloalkyl.3. The compound according to claim 1 , wherein Ris H claim 1 , —CH claim 1 , —CH claim 1 , —CH claim 1 , —OCH claim 1 , —OCH claim 1 , —OCH claim 1 , -cyclopropyl claim 1 , -cyclobutyl claim 1 , -cyclopentyl or -cyclohexyl.4. The compound according to claim 1 , wherein Rand Rare each independently H claim 1 , methyl claim 1 , ethyl claim 1 , propyl claim 1 , n-butyl claim 1 , n-pentyl claim 1 , n-hexyl claim 1 , n-heptyl claim 1 , n-octyl claim 1 , cyclopropyl claim 1 , cyclobutyl claim 1 , cyclopentyl claim 1 , cyclohexyl claim 1 , —CH(CH)NH claim 1 , —CH(CH)NH claim 1 , —CH(CH)NH claim 1 , —CH(CH)NH claim 1 , —N(CH)(CH)NH claim 1 , N(CH)(CH)NH claim 1 , N(CH)(CH)NHor N(CH)(CH)NH.5. The compound according to claim 1 , wherein when taken together claim 1 , Rand Rwith a nitrogen to which they are both attached form a form a 5 to 7 membered heterocyclic ring wherein any one carbon atom of said heterocyclic ring can optionally be replaced with —O— claim 1 , —S— claim 1 , —SO— or —NR—.7. The compound according to claim 1 , wherein Rand Rare each independently H or C-Calkyl.8. The compound according to claim 1 , wherein Rand Rform a six membered azaoxa-ring or azathia-ring.10. The compound according to claim 1 , wherein Zis a halide ion claim 1 , NO— claim 1 , CHCO— claim 1 , NO claim 1 , CHCO claim 1 , CFCO claim 1 , ClO claim 1 , HSO claim 1 , HPO claim 1 , SCN claim 1 , FB claim 1 , lactate claim 1 , citrate claim 1 , tartrate claim 1 , malate claim 1 , glycolate claim 1 , glycerate claim 1 , gluconate claim 1 , glutamate claim 1 , or aspartate.11. The compound according to ...

Подробнее
Номер записи: 64
07-01-2021 дата публикации

AhR MODULATORS

Номер: US20210002297A1
Автор: Alam Muzaffar, BECK Hilary Plake, Dillon Michael Patrick, GONZALEZ-LOPEZ Marcos, JR. James Clifford, Sutton
Принадлежит:

Provided herein are compounds, compositions and methods of using the compounds and compositions for the treatment of diseases modulated, as least in part, by AhR. The compounds are represented by formulae: 2. The compound of wherein:the dashed bonds are single bonds;{'sup': 4', '4, 'vertex a is selected from the group consisting of O, S, N, CH(R) and N(R);'}{'sup': 4', '4, '4 each of ring vertices b, c, d, e, f, and g are independently selected from the group consisting of O, S, N, C(R) and N(R), and'}the bonds joining the ring vertices are independently single or double bonds.3. The compound of wherein Z has subformula A′.4. (canceled)5. The compound of wherein Z has subformula C′.6. (canceled)7. (canceled)9. (canceled)10. (canceled)12. The compound of wherein W is —C(O)—.13. The compound of wherein W is —SO—.14. The compound of wherein W is —C(O)—.15. The compound of wherein W is —SO—.16. The compound of wherein Xis N.17. The compound of wherein Xis N.18. (canceled)19. The compound of wherein Ris selected from the group consisting of H claim 16 , deuterium claim 16 , halogen claim 16 , Calkyl claim 16 , —O Calkyl claim 16 , Chaloalkyl claim 16 , and —OChaloalkyl.20. (canceled)21. The compound of wherein R claim 19 , Rand Rare each independently selected from the group consisting of H claim 19 , deuterium claim 19 , halogen claim 19 , Calkyl claim 19 , Chaloalkyl and OChaloalkyl.22. The compound of wherein R claim 21 , R claim 21 , R claim 21 , Rare independently selected from the group consisting of H claim 21 , deuterium claim 21 , halogen claim 21 , Calkyl and Chaloalkyl.23. (canceled)24. (canceled)25. (canceled)26. (canceled)27. The compound of wherein each Ris independently selected from the group consisting of H claim 22 , halogen claim 22 ,{'sup': f', 'd', 'd', 'e', 'd, 'sub': '2', 'CN, —R, —COR, —CONRR, —C(O)R,'}{'sup': e', 'd', 'e', 'f', 'd', 'd', 'e', 'd', 'e', 'd', 'a', 'a', 'd', 'a', 'd', 'e', 'a', 'd', 'a', 'd', 'e', 'a', 'e', 'd', 'a', 'e', 'f', 'a', ...

Подробнее
Номер записи: 65
13-01-2022 дата публикации

RIP1K INHIBITORS

Номер: US20220009936A1
Автор: BHMIDIPATI Somasekhar, Darwish Ihab, Irving Mark, Kolluri Rao, Masuda Esteban, Shaw Simon, Taylor Vanessa, Yu Jiaxin
Принадлежит:

Disclosed herein are kinase inhibitory compounds, such as a receptor-interacting protein-1 (RIP1) kinase inhibitor compounds, as well as pharmaceutical compositions and combinations comprising such inhibitory compounds. The disclosed compounds, pharmaceutical compositions, and/or combinations may be used to treat or prevent a kinase-associated disease or condition, particularly a RIP1-associated disease or condition. 9. The compound according to claim 1 , wherein X is O.10. The compound according to wherein Yis N.11. The compound according to wherein Y claim 1 , Yand Yare each N.12. The compound according to wherein Yis O.13. The compound according to wherein Yis C═O.14. The compound according to wherein Y claim 1 , Yand Yare each C(R).15. The compound of claim 14 , wherein at least one Rof Y claim 14 , Yand Yis halo.16. The compound according to wherein m is zero.17. The compound according to wherein at least one Ris a linker-Rgroup.21. The compound according to wherein W is pyridyl.23. The compound according to wherein the compound is present in a salt form.24. A method for treating a RIP1K associated condition in a subject claim 1 , comprising administering to the subject a therapeutically effective amount of a compound according to . The present disclosure concerns compounds and methods of making and using the compounds, such as for inhibiting receptor-interacting protein-1 kinase (“RIP1”), and for treating diseases and/or conditions related to RIP1.Receptor-interacting protein-1 kinase (referred to herein as “RIP1”) belongs to the tyrosine kinase-like family and is a serine/threonine protein kinase involved in innate immune signaling. RIP1 plays a central role in regulating cell signaling and its role in programmed cell death has been linked to various inflammatory diseases, such as inflammatory bowel disease, psoriasis, and other diseases and/or conditions associated with inflammation and/or necroptotic cell death.Disclosed herein are compounds according to ...

Подробнее
Номер записи: 66
12-01-2017 дата публикации

HETEROCYCLIC COMPOUNDS

Номер: US20170008888A1
Автор: Cociorva Oana M., HU Yi, Li Bei, Lin Emme C. K., ROSENBLUM Jonathan S., SETO Shigeki, Shreder Kevin R., Sidique Shyama
Принадлежит:

Provided herein are compounds of formula I and compositions containing the compounds. The compounds and compositions are useful in the methods of inhibiting the action of ERK5, a BET family protein or both. In certain embodiments, the compounds and compositions are useful in the prevention, amelioration or treatment of a ERK5-mediated disease, a BET protein-mediated disease or both. 2. The compound of claim 1 , wherein{'sup': 7', '7', '8, 'Y is CRor CRR;'}{'sup': 9', '9', '10', '7', '9', '8', '10, 'Z is CRor CRR; wherein Rand Rtogether with the atoms on which they are substituted form a 3 to 6-membered cycloalkyl, aryl, heterocyclyl or heteroaryl ring; and Rand R, when present, are each independently selected from hydrogen, alkyl and cycloalkyl.'}3. The compound of claim 1 , wherein Ris phenyl claim 1 , pyridinyl claim 1 , cyclohexyl claim 1 , tetrahydropyranyl or pyrazolyl claim 1 , where Ris optionally substituted with 1 or 2 substituents Q.6. The compound of claim 4 , wherein Qis alkoxy.7. The compound of claim 4 , wherein Qis ethoxy.9. The compound of claim 8 , wherein{'sup': '3', 'sub': '0-2', 'X is NR, O or S(O);'}{'sup': '2', 'Ris alkyl or deuteroalkyl;'}{'sup': 3', '19, 'sub': '2', 'Ris alkyl, deuteroalkyl, cycloalkyl or SOR;'}{'sup': '4', 'Rhydrogen or alkyl;'}{'sup': '19', 'Ris alkyl;'}{'sub': '2', 'E is CO or SO;'}{'sup': '1', 'Ris aryl, heteroaryl, heterocyclyl or cycloalkyl;'}{'sup': 1', '3', '3', 'u', 'x', 'u', 'y', 'z', 'u', 'y', 'z', 'u', 'y', 'z', 'u', 'x', 'w', '4', '4, 'sub': t', 't, 'claim-text': [{'sup': 'u', 'each Ris independently alkylene or a direct bond;'}, {'sup': 'w', 'Ris alkyl or amino;'}, {'sup': 'x', 'each Ris independently hydrogen, alkyl or hydroxyalkyl;'}, {'sup': y', 'z, 'Rand Rare each independently selected from (i) or (ii) below, {'sup': y', 'z', 'y', 'z', '5, '(i) Ris hydrogen or alkyl; and Ris hydrogen, alkyl, haloalkyl, hydroxyalkyl, alkoxyalkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkylalkyl, cycloalkenylalkyl, ...

Подробнее
Номер записи: 67
12-01-2017 дата публикации

BENZOTHIAZOLE MACROCYCLES AS INHIBITORS OF HUMAN IMMUNODEFICIENCY VIRUS REPLICATION

Номер: US20170008912A1
Автор: Naidu B. Narasimhulu, Patel Manoj
Принадлежит:

The disclosure generally relates to compounds of formula I, including compositions and methods for treating human immunodeficiency virus (HIV) infection. The disclosure provides novel inhibitors of HIV, pharmaceutical compositions containing such compounds, and methods for using these compounds in the treatment of HIV infection. 2. A compound of where Ris alkyl; Ris alkyl; Ris hydrogen; Ris Ar; Ris chromanyl; Xis CH claim 1 , O claim 1 , or NR; Xis alkylene; and Xis CH; or a pharmaceutically acceptable salt thereof.3. A compound of where Ris alkyl claim 1 , Ris alkyl and Ris hydrogen.4. A compound of where Ris Ar.5. A compound of where Ris Ar.6. A compound of where Ris (R)-piperazinyl.7. A compound of where Aris chromanyl.8. A compound of where Xis CH claim 1 , O claim 1 , or NR; Xis alkylene; and Xis CH.9. A compound of selected from the group consisting of{'sup': 6', '9', '10', '14', '2', '7', '15', '20', '31', '35, '(2S)-2-(tert-Butoxy)-2-[(22S)-4,17,22-trimethyl-21,30-dioxa-8-thia-37-azaheptacyclo[25.6.2.1,.1,.0,.0,.0,]heptatriaconta-1(33),2,4,6,9(37),10(36), 11,13,15(20),16,18,31,34-tridecaen-3-yl]acetic acid;'}{'sup': 6', '9', '10', '14', '2', '7', '15', '23', '18', '22', '34', '38, '(2S)-2-(tert-Butoxy)-2-[(25S)-4,19,21,25-tetramethyl-24,33-dioxa-8-thia-19,20,40-triazaoctacyclo[28.6.2.1,.1,.0,.0,.0,.0,]tetraconta-1(36),2,4,6,9(40),10(39),11,13,15(23),16,18(22),20,34,37-tetradecaen-3-yl]acetic acid;'}{'sup': 6', '9', '10', '14', '2', '7', '15', '23', '17', '21', '34', '38, '(2S)-2-(tert-Butoxy)-2-[(25S)-4,20,25-trimethyl-24,33-dioxa-8-thia-12,19,20,39,40-pentaazaoctacyclo[28.6.2.1,.1,.0,.0,.0,.0,]tetraconta-1(36),2,4,6,9(40),10(39),11,13,15(23),16,18,21,34,37-tetradecaen-3-yl]acetic acid;'}{'sup': 6', '9', '10', '14', '2', '7', '15', '20', '31', '35, '(2S)-2-(tert-Butoxy)-2-[(22S)-4,22-dimethyl-18-(4-methylpiperazin-1-yl)-21,30-dioxa-8-thia-13,19,37-triazaheptacyclo[25.6.2.1,.1,.0,.0,.0,]heptatriaconta-1(33),2,4,6,9(37),10(36),11,13,15(20),16,18,31,34- ...

Подробнее
Номер записи: 68
14-01-2016 дата публикации

BICYCLIC HETEROAROMATIC CARBOXAMIDE COMPOUNDS USEFUL AS PIM KINASE INHIBITORS

Номер: US20160009726A1
Автор: Li Yun-Long, Vechorkin Oleg, Zhu Wenyu
Принадлежит:

The present disclosure describes bicyclic heteroaromatic carboxamide derivatives, as well as their compositions and methods of use. The compounds inhibit the activity of the Pim kinases, and are useful in the treatment of diseases related to the activity of Pim kinases including, e.g., cancer and other diseases. 2. The compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein{'sup': '6', 'sub': 6-10', '3-6, 'Cyis unsubstituted or substituted Caryl, unsubstituted or substituted 5-10 membered heteroaryl, unsubstituted or substituted Ccycloalkyl, or unsubstituted or substituted 4-12 membered heterocycloalkyl,'}{'sub': 6-10', '3-6', '2-6', '2-6', '1-6', '2', '2', '2, 'sup': 6', 'Cy6', 'a3', 'a3', 'b3', 'c3', 'd3', 'a3', 'b3', 'c3', 'd3', 'c3', 'd3', 'c3', 'b3', 'c3', 'c3', 'd3', 'c3', 'a3', 'e3', 'c3', 'd3', 'c3', 'e3', 'c3', 'd3', 'b3', 'c3', 'd3', 'b3', 'c3', 'b3', 'c3', 'd3, 'wherein the substituted Caryl, 5-10 membered heteroaryl, Ccycloalkyl or 4-12 membered heterocycloalkyl forming Cyis substituted with 1, 2, 3, 4 or 5 substituents each independently selected from halogen, R, Calkenyl, Calkynyl, Chaloalkyl, CN, OR, SR, C(O)R, C(O)NRR, C(O)OR, OC(O)R, OC(O)NRR, NRR, NRC(O)R, NRC(O)NRR, NRC(O)OR, C(═NR)NRR, NRC(═NR)NRR, S(O)R, S(O)NRR, S(O)R, NRS(O)Rand S(O)NRR.'}4. The compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein:{'sup': '1', 'Ris H; and'}{'sup': 2', 'a2', 'a2', 'b2', 'c2', 'd2', 'a2', 'b2', 'c2', 'd2', 'c2', 'd2', 'c2', 'b2', 'c2', 'c2', 'a2', 'c2', 'a2', 'e2', 'c2', 'd2', 'c2', 'e2', 'c2', 'd2', 'b2', 'c2', 'a2', 'b2', 'c2', 'b2', 'c2', 'd2, 'sub': 1-6', '2-6', '2-6', '1-6', '2', '2', '2, 'Ris H, halogen, Calkyl, Calkenyl, Calkynyl, Chaloalkyl, CN, OR, SR, C(O)R, C(O)NRR, C(O)OR, OC(O)R, OC(O)NRR, NRR, NRC(O)R, NRC(O)NRR, NRC(O)OR, C(═NR)NRR, NRC(═NR)NRR, S(O)R, S(O)NRR, S(O)R, NRS(O)Ror S(O)NRR.'}5. The compound of claim 4 , or a pharmaceutically acceptable salt thereof claim 4 , wherein Ris H ...

Подробнее
Номер записи: 69
14-01-2016 дата публикации

SUBSTITUTED THIAZOLOPYRIMIDINES

Номер: US20160009734A1
Автор: Graham Keith, Kettschau Georg, Klar Ulrich, Lienau Philip, Puehler Florian, SÜLZLE DETLEV, Wortmann Lars
Принадлежит: BAYER PHARMA AKTIENGESELLSCHAFT

The present invention relates to substituted thiazolopyrimidine compounds of general formula I as described and defined herein, to methods of preparing said compounds, to intermediate compounds useful for preparing said compounds, to pharmaceutical compositions and combinations comprising said compounds and to the use of said compounds for manufacturing a pharmaceutical composition for the treatment or prophylaxis of a disease, in particular of a hyperproliferative and/or angiogenesis disorder, as a sole agent or in combination with other active ingredients. 4. A compound according to claim 1 , wherein:{'sup': '1a', 'claim-text': {'sub': 1', '3', '1', '3, 'C-C-alkyl-, C-C-alkoxy-, halo-;'}, 'Rrepresents a hydrogen atom or a group selected from{'sup': 1b', '1c', '1d, 'R, R, Rrepresents a hydrogen atom.'}5. A compound according to claim 1 , wherein:{'sup': '1a', 'Rdoes not represent a hydrogen atom.'}6. A compound according to claim 1 , wherein:{'sup': '2', 'claim-text': [{'sub': 1', '6', '3', '6', '2', 'q', '2', 'p, 'sup': '3', 'C-C-alkyl-, C-C-cycloalkyl-, aryl-, cyano-, —(CH)—X—(CH)—R;'}, {'sub': 1', '6', '3', '6, 'sup': '4', 'wherein said C-C-alkyl-, C-C-cycloalkyl- or aryl- group is optionally substituted, identically or differently, with 1, 2 or 3 Rgroups;'}], 'Rrepresents a hydrogen atom, a halogen atom, or a group selected from {'sup': 3a', '3a, '—O—, —C(═O)—, —C(═O)—(NR)—, —(NR)—C(═O)—;'}, 'X represents a bond or a bivalent group selected from{'sup': '3a', 'sub': 1', '6', '3', '6, 'claim-text': {'sub': 1', '6', '3', '6, 'sup': '4', 'wherein said C-C-alkyl-, C-C-cycloalkyl-, 3- to 10-membered heterocycloalkyl- or aryl- group is optionally substituted, identically or differently, with 1, 2 or 3 Rgroups;'}, 'Rrepresents a hydrogen atom or a group selected from C-C-alkyl-, C-C-cycloalkyl-, 3- to 10-membered heterocycloalkyl-, aryl-;'}{'sup': 4', '5', '5', '5', '5', '5a', '5b, 'sub': 1', '6', '1', '6', '1', '6', '1', '6', '1', '6', '1', '6', '1', '6, 'Rrepresents ...

Подробнее
Номер записи: 70
09-01-2020 дата публикации

SOLID STATE FORMS OF MIDOSTAURIN

Номер: US20200010481A1
Автор: Ferenczi Renata Kertine, Juhasz Zsuzsa Potarine, Racz Csilla Nemethe, Struba Szabolcs, Tamas Tivadar
Принадлежит:

The present disclosure relates to solid state forms of Midostaurin, processes for preparation thereof, pharmaceutical compositions thereof, and use thereof in the treatment of Acute Myelogenous Leukemia (AML) and Aggressive Systemic Mastocytosis. Chemical SHNCH formula: CHNOMolecular mass: 570.64 g/mol 1. Crystalline Form VI of Midostaurin , which is characterized by data selected from one of the following:(i) an XRPD pattern having peaks at 7.5, 9.5, 11.0, 14.2 and 16.1 degrees 2-theta±0.2 degrees 2-theta;{'figref': {'@idref': 'DRAWINGS', 'FIG. 3'}, '(ii) an XRPD pattern as depicted in ; and'}combinations of any of (i) or (ii).2. Crystalline Form VI of Midostaurin according to which is characterized by data selected from one or more of the following:(i) an XRPD pattern having peaks at 7.5, 9.5, 11.0, 14.2 and 16.1 degrees 2-theta±0.2 degrees 2-theta, and also having one, two, three, four or five additional peaks selected from 17.3, 18.4, 20.4, 23.0, and 26.1 degrees 2-theta±0.2 degrees 2-theta;{'sup': −1', '−1, '(ii) an FT-IR spectrum having one, two, three, four or more peaks selected from 3428, 1701, 1635, 1454, 1345, 1223, 1115, 1064, 823, 750 and 713 cm±1 cm;'}{'figref': {'@idref': 'DRAWINGS', 'FIG. 17'}, '(iii) an FT-IR spectrum as depicted in ; and'}combinations of any of (i)-(iii).3. Crystalline Form VI of Midostaurin according to wherein crystalline Form VI is a hydrate.4. Crystalline Form VI of Midostaurin according to characterized by a water content of between 1 to 5%.5. Crystalline Form VI of Midostaurin according to characterized by a water content of about 2%.6. A pharmaceutical composition comprising a crystalline form according to .7. Use of the crystalline form according to in the preparation of pharmaceutical compositions and/or formulations.8. A pharmaceutical formulation comprising a crystalline form according to claim 1 , and at least one pharmaceutically acceptable excipient.9. The crystalline form according to claim 1 , for use as a ...

Подробнее
Номер записи: 71
09-01-2020 дата публикации

AZAPHENOTHIAZINES AND AZAPHENOXAZINES AS ANTIOXIDANTS

Номер: US20200010776A1
Автор: HAIDASZ Evan, Pratt Derek Andrew
Принадлежит:

The present disclosure relates generally to antioxidants. More particularly, the present disclosure relates to lubricating compositions comprising an antioxidant. 2. The compound of claim 1 , where said electron donating group is an H atom claim 1 , a hydrocarbon group claim 1 , an aryl group claim 1 , an alkyl group claim 1 , an alkoxy group claim 1 , an amine group claim 1 , a monosubstituted amine claim 1 , or a disubstituted amine.13. A lubricant composition claim 1 , comprising:{'claim-ref': [{'@idref': 'CLM-00001', 'claims 1'}, {'@idref': 'CLM-00012', '12'}], 'an oil of lubricating viscosity, and a compound of any one of to .'}14. The lubricant of claim 13 , wherein said oil of lubricating viscosity comprises a natural oil claim 13 , a synthetic oil claim 13 , or a mixture of a natural oil and a synthetic oil.15. The lubricant of claim 13 , where said oil of lubricating viscosity comprises an API base oil of Group I claim 13 , Group II claim 13 , Group III claim 13 , Group IV claim 13 , or Group V.16. The lubricant of any one of to claim 13 , further comprising an additive.17. The lubricant of claim 16 , wherein said additive comprises one or more of a metal deactivator claim 16 , a detergent claim 16 , a friction modifier claim 16 , an antiwear agent claim 16 , a rust inhibitor claim 16 , a dispersant claim 16 , a viscosity index improver claim 16 , an extreme pressure agent claim 16 , an additional antioxidant claim 16 , a foam inhibitors claim 16 , a pour point depressant claim 16 , a seal swelling agent.18. Use of a lubricant composition according to any one of to as a lubricant for a combustion engine.19. A method of forming a lubricant composition claim 16 , comprising: combining an oil of lubricating viscosity claim 16 , providing with an antioxidant according to any one of to .20. The method of claim 19 , wherein said oil of lubricating viscosity comprises a natural oil claim 19 , a synthetic oil claim 19 , or a mixture of a natural oil and a synthetic ...

Подробнее
Номер записи: 72
14-01-2021 дата публикации

COMPOUND FOR ORGANIC ELECTRIC ELEMENT, ORGANIC ELECTRIC ELEMENT COMPRISING THE SAME, AND ELECTRONIC DEVICE THEREOF

Номер: US20210013420A1
Автор: KANG Byoung Yeop, KIM Won Sam, LEE Hyung Dong, OH Dae Hwan, SO Ki Ho
Принадлежит: DUK SAN NEOLUX CO., LTD.

Provided are a compound represented by Formula 1, an organic electric element comprising a first electrode, a second electrode, and an organic material layer formed between the first electrode and the second electrode, and an electronic device thereof, wherein by comprising compound represented by Formula 1 in the organic material layer, the driving voltage of the organic electric element can be lowered, and the luminous efficiency and life time, in particular, life time can be improved. 5. The compound of claim 1 , wherein at least one of Lto Lis a single bond.7. An organic electric element comprising an anode claim 1 , a cathode claim 1 , and an organic material layer formed between the anode and the cathode claim 1 , wherein the organic material layer comprises a single compound or a mixture of two or more compounds represented by Formula 1 of .8. An organic electric element comprising an anode claim 1 , a cathode claim 1 , an organic material layer formed between the anode and the cathode claim 1 , and a layer for improving luminous efficiency claim 1 , wherein the layer for improving luminous efficiency is formed on one side of the anode and/or the cathode claim 1 , the one side not facing the organic material layer claim 1 , and the organic material layer or the layer for improving luminous efficiency comprises a single compound or a mixture of two or more compounds represented by Formula 1 of .9. The organic electric element of claim 7 , wherein the organic material layer comprises at least one of a hole injection layer claim 7 , a hole transport layer claim 7 , an emission-auxiliary layer claim 7 , a light emitting layer claim 7 , an electron transport-auxiliary layer claim 7 , an electron transport layer and an electron injection layer.10. The organic electric element of claim 9 , wherein the compound is comprised in the emission-auxiliary layer.11. The organic electric element of claim 7 , wherein the organic material layer comprises two or more stacks and ...

Подробнее
Номер записи: 73
19-01-2017 дата публикации

POLYMORPHIC MIXTURE OF RIFAXIMIN AND ITS USE FOR THE PREPARATION OF SOLID FORMULATIONS

Номер: US20170015682A1
Автор: Argese Maria, Fumagalli Emanuela, Grilli Maria Donata, Grisenti Paride, Motta Giuseppe, Pengo Daniele
Принадлежит:

A Rifaximin polymorphic mixture of α/β form in a relative ratio of 85/15±3 and a process for its preparation. The polymorphic mixture of Rifaximin is for use as a medicament, in particular in the treatment of traveler's diarrhea and hepatic encephalopathy. A pharmaceutical composition comprises the polymorphic mixture of Rifaximin as active ingredient, in particular, a solid formulation, more in particular, a film coated tablet. A polymorphic form of crude wet rifaximin and of purified wet rifaximin their use are used as intermediates in a process for the preparation of Rifaximin polymorphic mixture of α/β form in a relative ratio of 85/15±3. 1. A Rifaximin polymorphic mixture of α/β form in a relative ratio of 85/15±3.2. A process for the preparation of a Rifaximin polymorphic mixture , comprising:a) reacting a molar equivalent of Rifamycin O with 2 or 3 equivalents of 2-amino-4-methylpyridine in a solvent mixture of water and ethyl alcohol in a volumetric ratio between 1:2 and 1:3, at a temperature between 20° C. and 30° C., to give a reaction mass;b) treating said reaction mass at 20-30° C. with ascorbic acid, then with a mixture of water and ethyl alcohol and concentrated aqueous hydrochloric acid, and adjusting the pH of the reaction mass to 6.0-6.5, to obtain a suspension;c) filtering the suspension to obtain a first solid, washing the first solid with a water/ethyl alcohol solvent mixture to obtain crude wet Rifaximin;d) purifying the crude wet Rifaximin by dissolving the crude wet Rifaximin in ethyl alcohol at a temperature between 50° C. and 60° C. and precipitating wet purified Rifaximin by adding water and lowering the temperature to between 28-33° C. under stirring for a period of 1-3 hours, cooling to 20-25° C. under stirring for 1-2 hours, and then cooling to 0-5° C. under stirring to obtain a precipitate of wet purified Rifaximin;e) filtering the wet purified Rifaximin to obtain a second solid, washing the second solid with water, andf) drying the ...

Подробнее
Номер записи: 74
19-01-2017 дата публикации

PYRAZOLOPYRIMIDINE MACROCYCLES AS INHIBITORS OF HUMAN IMMUNODEFICIENCY VIRUS REPLICATION

Номер: US20170015683A1
Автор: Kadow John F., Langley David R., Naidu B. Narasimhulu, Peese Kevin, WANG ZHONGYU
Принадлежит:

The disclosure generally relates to compounds of formula I, including compositions and methods for treating human immunodeficiency virus (HIV) infection. The disclosure provides novel inhibitors of HIV, pharmaceutical compositions containing such compounds, and methods for using these compounds in the treatment of HIV infection. 2. A compound of where Ris alkyl; Ris alkyl; Ris hydrogen; Ris azetidinyl claim 1 , pyrrolidinyl claim 1 , piperidinyl claim 1 , piperazinyl claim 1 , morpholinyl claim 1 , homopiperidinyl claim 1 , homopiperazinyl claim 1 , or homomorpholinyl substituted with 0-3 alkyl substituents; Aris phenyl substituted with 0-3 substituents selected from cyano claim 1 , halo claim 1 , alkyl claim 1 , haloalkyl claim 1 , alkoxy claim 1 , and haloalkoxy; Aris pyrrolyl claim 1 , furanyl claim 1 , thienyl claim 1 , pyrazolyl claim 1 , isoxazolyl claim 1 , isothiazolyl claim 1 , imidazolyl claim 1 , oxazolyl claim 1 , thiazolyl claim 1 , triazolyl claim 1 , oxadiazolyl claim 1 , or thiadiazolyl claim 1 , and is substituted with 0-3 alkyl substituents; Xis CHor O; Xis alkylene or alkenylene; and Xis CH claim 1 , CHor O; or a pharmaceutically acceptable salt thereof.3. A compound of where Ris piperidinyl substituted with 0-1 alkyl substituents; Aris phenyl; Aris pyrazolyl claim 2 , imidazolyl claim 2 , or thiazolyl substituted with 0-3 alkyl substituents; Xis CHor O; Xis alkylene or alkenylene; and Xis CH claim 2 , CHor O; or a pharmaceutically acceptable salt thereof.4. A compound of where Ris alkyl claim 1 , Ris alkyl and Ris hydrogen.5. A compound of where Ris piperidinyl substituted with 0-3 alkyl substituents.6. A compound of where Aris phenyl.7. A compound of where Aris pyrazolyl claim 1 , imidazolyl claim 1 , or thiazolyl substituted with 0-3 alkyl substituents.8. A compound of Xis CHor O; Xis alkylene or alkenylene; and Xis CH claim 1 , CHor O.9. A compound of where Xis CH; Xis alkylene or alkenylene; and Xis CH.10. A compound of selected from the ...

Подробнее
Номер записи: 75
21-01-2016 дата публикации

C2-AZASPIRO IMINOTHIAZINE DIOXIDES AS BACE INHIBITORS, COMPOSITIONS, AND THEIR USE

Номер: US20160016975A1
Автор: Burnett Duane A., Cumming Jared N., Gilbert Eric J., Scott Jack D., Stamford Andrew W., Wu Wen-Lian
Принадлежит: Merck Sharp & Dohme Corp.

In its many embodiments, the present invention provides certain C2-azaspiro substituted iminothiazine dioxide compounds. The novel compounds of the invention are useful as BACE inhibitors and/or for the treatment and prevention of various pathologies related thereto. Pharmaceutical compositions comprising one or more such compounds (alone and in combination with one or more other active agents), and methods for their preparation and use, including for the possible treatment of Alzheimer's disease, are also disclosed. 2. A compound of claim 1 , or a tautomer thereof claim 1 , or a pharmaceutically acceptable salt of said compound or said tautomer claim 1 , wherein:{'sup': '2', 'each Ris H;'}{'sup': '3', 'each R(when present) is H;'}{'sup': '1A', 'Ris H;'}{'sup': '1B', 'Ris H;'}{'sup': '4', 'sub': '2', 'Ris selected from the group consisting of methyl and —CHF; and'}{'sup': 'N', 'sub': 3', '3', '2', '3', '2', '3', '2', '2', '3', '2', '3', '2', '3', '2', '2', '3', '2', '2', '3', '2', '2', '2', '2, 'Ris selected from the group consisting of H, —C(O)CH, —C(O)OCH, —C(O)OCHCH, —C(O)OCHCH(CH), —C(O)O-cyclopropyl, —C(O)O—CH-cyclopropyl, —C(O)N(CH), —C(O)NHCH, C(O)-aryl, C(O)-heteroaryl, —S(O)CH, —S(O)-cyclopropyl, —S(O)N(CH), —S(O)NHCH, —S(O)-aryl, —S(O)-heteroaryl, methyl, ethyl, propyl, isopropyl, cyclopropyl, —CH-cyclopropyl, benzyl, phenyl, pyridyl, pyrimidinyl, pyrazinyl, oxadiazoyl, isoxazoyl, oxazoyl, pyrrolyl, thiazolyl, isothiazolyl, thiadiazolyl, imidazolyl, —CH-heteroaryl,'}{'sub': 2', '2', '2, 'sup': N', '9, 'wherein said benzyl, phenyl, pyridyl, oxadiazoyl, isoxazoyl, oxazoyl, pyrrolyl, thiazolyl, isothiazolyl, thiadiazolyl, imidazolyl, —CH-heteroaryl, C(O)-aryl, C(O)-heteroaryl, —S(O)-aryl, —S(O)-heteroaryl of Rare each optionally unsubstituted or substituted with R.'}3. A compound of claim 2 , or a tautomer thereof claim 2 , or a pharmaceutically acceptable salt of said compound or said tautomer claim 2 , wherein:{'sup': 'N', 'sub': 3', '2', '3', '3', '2', '2, ...

Подробнее
Номер записи: 76
15-01-2015 дата публикации

Glycosidase inhibitors

Номер: US20150018318A1
Автор: Donnelly Marianne, Goutopoulos Andreas, Liu-Bujalski Lesley, Qiu Hui, Yu Henry
Принадлежит:

Novel compounds of formula (I) 2. The method according to claim 1 , wherein the condition is selected from the group of tauopathy claim 1 , Amyotrophic lateral sclerosis (ALS) claim 1 , Amyotrophic lateral sclerosis with cognitive impairment (ALSci) claim 1 , Argyrophilic grain dementia claim 1 , Bluit disease claim 1 , Corticobasal degeneration (CBP) claim 1 , Dementia pugilistica claim 1 , Diffuse neurofibrillary tangles with calcification claim 1 , Down's syndrome claim 1 , Familial British dementia claim 1 , Familial Danish dementia claim 1 , Frontotemporal dementia with parkinsonism linked to chromosome 17 (FTDP-17) claim 1 , Gerstmann-Straussler-Scheinker disease claim 1 , Guadeloupean parkinsonism claim 1 , Hallevorden-Spatz disease (neurodegeneration with brain iron accumulation type 1) claim 1 , Multiple system atrophy claim 1 , Myotonic dystrophy claim 1 , Niemann-Pick disease (type C) claim 1 , Pallido-ponto-nigral degeneration claim 1 , Parkinsonism-dementia complex of Guam claim 1 , Pick's disease (PiD) claim 1 , Postencephalitic parkinsonism (PEP) claim 1 , Prion diseases (including Creutzfeldt-Jakob Disease (GJD) claim 1 , Variant Creutzfeldt-Jakob Disease (vCJD) claim 1 , Fatal Familial Insomnia claim 1 , Kuru claim 1 , Progressive supercortical gliosis claim 1 , Progressive supranuclear palsy (PSP) claim 1 , Richardson's syndrome claim 1 , Subacute sclerosing panencephalitis claim 1 , Tangle-only dementia claim 1 , Huntington's disease and Parkinson's disease.3. The method according to for treating a tauopathy.4. The method according to claim 1 , wherein the condition is selected from the group of Progressive supranuclear palsy (PSP) claim 1 , Frontotemporal dementia with parkinsonism linked to chromosome 17 (FTDP-17) claim 1 , Corticobasal degeneration (CBP) and Pick's disease (PiD).5. The method according to claim 1 , wherein{'sup': 1', '2', '3, 'R, R, Rdenote independently from one another H or A.'}6. The method according to claim 5 , wherein{' ...

Подробнее
Номер записи: 77
17-01-2019 дата публикации

COMPOUNDS THAT INHIBIT MCL-1 PROTEIN

Номер: US20190016736A1
Автор: Brown Sean P., GONZALEZ BUENROSTRO Ana, LI Yunxiao, LI Zhihong, LIZARZABURU Mike Elias, Lucas Brian S., Paras Nick A., TAYGERLY Joshua, VIMOLRATANA Marc, Wang Xianghong, Yu Ming, ZANCANELLA Manuel, ZHU Liusheng
Принадлежит: Amgen Inc.

Provided herein are compounds that are useful intermediates that may used to synthesize myeloid cell leukemia 1 protein (Mcl-1) inhibitors. Also provided are Mcl-1 inhibitors, methods of their preparation, related pharmaceutical compositions, and methods of using the same. For example, provided herein are compounds of Formula I, This application is a continuation of U.S. patent application Ser. No. 15/376,456, filed Dec. 12, 2016, which is a continuation of U.S. patent application Ser. No. 14/839,149, filed Aug. 28, 2015, now U.S. Pat. No. 9,562,061, which claims the benefit of U.S. Provisional Patent Application No. 62/043,929, filed Aug. 29, 2014, now expired, each of which is hereby incorporated by reference in its entirety and for all purposes as if fully set forth herein.The present invention relates to compounds that inhibit myeloid cell leukemia 1 protein (Mcl-1, also abbreviated as MCL-1 or MCL1); methods of treating diseases or conditions, such as cancer, using the compounds; and pharmaceutical compositions containing the compounds.One common characteristic of human cancer is overexpression of Mcl-1. Mcl-1 overexpression prevents cancer cells from undergoing programmed cell death (apoptosis), allowing the cells to survive despite widespread genetic damage.Mcl-1 is a member of the Bcl-2 family of proteins. The Bcl-2 family includes pro-apoptotic members (such as BAX and BAK) which, upon activation, form a homo-oligomer in the outer mitochondrial membrane that leads to pore formation and the escape of mitochondrial contents, a step in triggering apoptosis. Antiapoptotic members of the Bcl-2 family (such as Bcl-2, Bcl-XL, and Mcl-1) block the activity of BAX and BAK. Other proteins (such as BID, BIM, BIK, and BAD) exhibit additional regulatory functions.Research has shown that Mcl-1 inhibitors can be useful for the treatment of cancers. MCI-1 is overexpressed in numerous cancers. See Beroukhim et al. (2010) Nature 463, 899-905. Cancer cells containing ...

Подробнее
Номер записи: 78
28-01-2016 дата публикации

FLUORESCENT COMPOUNDS AND USES THEREOF

Номер: US20160024067A1
Автор: Cheung Chingying, Leung Wal-Yee, Mao Fei, ROBERTS Lori M., Windler Sarah Lynn
Принадлежит:

The invention provides compounds, including fluorescent nucleic acid dyes, and methods for use including nucleic acid detection, nucleic acid amplification reactions, and high-resolution melt curve analysis. Further provided are kits, instruments and systems comprising compounds of the invention or adapted for use with compounds of the invention or other nucleic acid dyes. 2. The compound of claim 1 , wherein Ris C-Calkyl claim 1 , optionally substituted with —NRRor —NRRR; or Ris L-G.3. The compound of claim 1 , wherein Ris C-Calkyl.4. The compound of claim 1 , wherein Lis a C-Calkyl group.5. The compound of claim 1 , wherein Lis a C-Calkyl group.6. The compound of claim 1 , wherein Lis a C-Calkyl group.7. The compound of claim 1 , wherein L claim 1 , Lor Lis a C-Calkyl group wherein at least one methylene is replaced with —O— claim 1 , —S— claim 1 , or —NR— claim 1 , where Ris H claim 1 , C-Calkyl claim 1 , heteroalkyl claim 1 , aryl claim 1 , or heteroaryl.9. The compound of claim 1 , wherein W is +1 claim 1 , a is 1 claim 1 , and Rand Rin combination form a 5-9 membered ring.10. The compound of claim 1 , wherein W is +1 claim 1 , a is 1 claim 1 , and Rand Rin combination form a 5-9 membered ring.12. The compound of claim 11 , wherein Rand Rin combination form a 5-9 membered ring.13. The compound of claim 11 , wherein n is 0 claim 11 , and Ris H.14. The compound of claim 11 , wherein R claim 11 , Rand Rare H.15. The compound of or claim 11 , wherein Gis substituted or unsubstituted guanidino claim 11 , or substituted or unsubstituted amidino.19. The compound of claim 18 , wherein Q is Q1 claim 18 , Q5 claim 18 , Q6 claim 18 , or Q7.20. The compound of claim 1 , wherein Ris L-G.21. The compound of claim 1 , wherein Ris L-G.22. The compound of claim 1 , wherein Ris V.2328.-. (canceled)30. The compound of claim 29 , wherein Gis selected from the group consisting of substituted or unsubstituted guanidino and substituted or unsubstituted amidino.33. The compound of ...

Подробнее
Номер записи: 79
28-01-2016 дата публикации

INHIBITORS OF HUMAN IMMUNODEFICIENCY VIRUS REPLICATION

Номер: US20160024077A1
Автор: Connolly Timothy P., Naidu B. Narasimhulu, Patel Manoj
Принадлежит:

The disclosure generally relates to compounds of formula (I), including compositions and methods for treating human immunodeficiency virus (HIV) infection. The disclosure provides novel inhibitors of HIV, pharmaceutical compositions containing such compounds, and methods for using these compounds in the treatment of HIV infection. 2. A compound of where:{'sup': 1', '7', '8, 'Ris —CON(R)(R);'}{'sup': 1', '1', '1', '1, 'or Ris pyrrolyl, furanyl, thienyl, pyrazolyl, isoxazolyl, isothiazolyl, imidazolyl, oxazolyl, thiazolyl, triazolyl, oxadiazolyl, thiadiazolyl, indolyl, benzofuranyl, benzothiophenyl, benzimidazolyl, or phenyl, and is substituted with 0-3 substituents selected from halo, alkyl, haloalkyl, alkenyl, Ar, (Ar)alkyl, and (Ar)O;'}{'sup': '2', 'Ris hydrogen or alkyl;'}{'sup': '3', 'Ris azetidinyl, pyrrolidinyl, piperidinyl, piperazinyl, morpholinyl, homopiperidinyl, homopiperazinyl, or homomorpholinyl, and is substituted with 0-3 substituents selected from halo, alkyl, haloalkyl, hydroxyalkyl, alkoxyalkyl, alkenyl, cycloalkyl, hydroxy, alkoxy, haloalkoxy, alkenyloxy, and phenyl;'}{'sup': '3', 'or Ris cycloalkyl, cycloalkenyl, chromanyl, oxazinyl, or dihydropyranoquinolinyl, and is substituted with 0-3 substituents selected from halo, alkyl, haloalkyl, hydroxyalkyl, alkoxyalkyl, alkenyl, cycloalkyl, hydroxy, alkoxy, haloalkoxy, alkenyloxy, and phenyl;'}{'sup': '4', 'Ris alkyl or haloalkyl;'}{'sup': '5', 'Ris alkyl;'}{'sup': '6', 'Ris hydrogen or alkyl;'}{'sup': 7', '1', '1, 'Ris Aror (Ar)alkyl;'}{'sup': '8', 'Ris hydrogen or alkyl;'}{'sup': '1', 'Aris phenyl or pyridinyl and is substituted with 0-3 substituents selected from halo, cyano, alkyl, haloalkyl, alkoxy, haloalkoxy, and alkenyloxy;'}{'sup': '1', 'Xis pyrrolyl, furanyl, thienyl, pyrazolyl, isoxazolyl, isothiazolyl, imidazolyl, oxazolyl, thiazolyl, triazolyl, oxadiazolyl, thiadiazolyl, benzimidazolyl, or phenyl;'}{'sup': '2', 'Xis benzyl wherein the benzyl can be substituted with 0-3 substituents ...

Подробнее
Номер записи: 80
28-01-2016 дата публикации

HEDGEHOG PATHWAY SIGNALING INHIBITORS AND THERAPEUTIC APPLICATIONS THEREOF

Номер: US20160024095A1
Автор: Zhang Xiaohu
Принадлежит:

The hedgehog (Hh) signaling pathway is a pathway which regulates patterning, growth and cell migration during embryonic development, but in adulthood is limited to tissue maintenance and repair. Mutational inactivation of the inhibitory pathway components leads to constitutive ligand-independent activation of the Hh signaling pathway, results in cancers such as basal cell carcinoma and medulloblastoma. Ligand-dependent activation of Hh signaling is involved in prostate cancer, pancreatic cancer, breast cancer and some blood cancers. Therefore, inhibition of the aberrant Hh signaling represents a promising approach toward novel anticancer therapy. The present invention provides novel molecules of formula I that inhibit hedgehog pathway signaling and provides therapeutic applications for the treatment of malignancies (basal cell carcinoma, medulloblastoma, glioblastoma, non-small cell lung cancer, prostate cancer, pancreatic cancer, blood cancers, mesenchymal cancers, etc.), prevention of tumor regrowth, sensitization of radio-chemo therapies, and other diseases (inflammation, fibrosis and immune disorders) related to hedgehog signaling. 110-. (canceled)20. The compound of claim 19 , wherein U is selected from a group consisting of pyridine claim 19 , pyrazine claim 19 , quinoline claim 19 , and thiazole claim 19 , with 0-2 substituents.22. A pharmaceutical composition comprising a compound of formula I in and a pharmaceutically acceptable carrier. This application claims the benefit of Chinese Patent Applications 201310014254.4, filed on Jan. 15, 2013; 201310057744.2, filed on Feb. 25, 2013; 201310465383.5, filed on Oct. 8, 2013; 201310463448.2, filed on Oct. 8, 2013; and 201310485380.8, filed on Oct. 16, 2013; all of which are hereby incorporated by reference.The present invention generally relates to heterocyclic compounds and, more particularly, relates to novel heterocyclic compounds that are useful in therapies targeting the hedgehog signaling pathway mediated ...

Подробнее
Номер записи: 81
28-01-2016 дата публикации

MACROCYCLIC SALT-INDUCIBLE KINASE INHIBITORS

Номер: US20160024113A1
Автор: Benderitter Pascal Andre, Blom Petra Marcella, Cyriel, Françoise, HOFLACK Jan Marie, Jozef, Rene
Принадлежит: ONCODESIGN S.A.

The present invention relates to macrocyclic compounds and compositions containing said compounds acting as kinase inhibitors, in particular as inhibitors of SIK kinase, more in particular SIK1, SIK2 and/or SIK3 and/or mutants thereof, for use in the diagnosis, prevention and/or treatment of SIK-kinase associated diseases. Moreover, the present invention provides methods of using said compounds, for instance as a medicine or diagnostic agent. 2. The method of claim 1 , wherein:{'sub': 1', '2, 'Ais C and Ais N;'}{'sub': 1', '41', '1-6', '1-6', '1-6', '9', '10', '4', '4', '2', '4', '9', '2', '4', '3-6', '7', '1', '1-6', '11', '12', '1-6', '1-6, 'Rand Rare each independently selected from —H, -halo, —OH, —Calkyl, —O—Calkyl, —S—Calkyl, —NRR, —(C═O)—R, —(C═S)—R, —SO—R, —CN, —NR—SO—R, —Ccycloalkyl, —Arand -Het; wherein each of said —Calkyl is optionally and independently substituted with from 1 to 3 substituents selected from -halo, —OH, —NRR, —O—Calkyl, and —S—Calkyl;'}{'sub': 2', '1-6', '1-6', '1-6', '1-6', '1-6', '1-6', '1-6', '27', '28', '27', '28', '3-6', '3', '2', '3', '3', '2', '2', '3-6', '3-6', '2', '1-6', '1-6', '1-6', '1-6', '3', '2', '13', '14, 'Ris selected from —H, -halo, —OH, —Calkyl, —O—Calkyl, —S—Calkyl, —(C═O)—Calkyl, —(C═S)—Calkyl, —(C═O)—O—Calkyl, —(C═S)—O—Calkyl, —(C═O)—NRR, —(C═S)—NRR, —Ccycloalkyl, -Het, —Ar, —(C═O)-Het, —(C═S)-Het, —(C═O)—Ar, —(C═S)—Ar, —(C═O)—Ccycloalkyl, —(C═S)—Ccycloalkyl, and —SO—Calkyl; wherein each of said —Calkyl is optionally and independently substituted with from 1 to 3 substituents selected from -halo, —OH, —O—Calkyl, —S—Calkyl, -Het, —Ar, and —NRR;'}{'sub': 3', '1-6', '1-6', '1-6', '1-6', '1-6', '1-6', '1-6', '29', '30', '29', '30', '3-6', '2', '3', '2', '2', '3', '3', '3-6', '3-6', '2', '1-6', '1-6', '1-6', '1-6', '3-6', '2', '3', '15', '16, 'Ris selected from —H, -halo, —OH, —Calkyl, —O—Calkyl, —S—Calkyl, —(C═O)—Calkyl, —(C═S)—Calkyl, —(C═O)—O—Calkyl, —(C═S)—O—Calkyl, —(C═O)—NRR, —(C═S)—NRR, —Ccycloalkyl -Het, —Ar, —( ...

Подробнее
Номер записи: 82
26-01-2017 дата публикации

OPIOID AGONISTS AND USES THEREOF

Номер: US20170022167A1
Автор: Anand Neel K., Duarte Franco J., Sharma Pankaj, Singh Devendrapratap
Принадлежит:

Provided are compounds, including those of Formula I; and pharmaceutically acceptable salts and solvates thereof. The compounds described herein relate to and/or have application(s) in (among others) the fields of drug discovery, pharmacotherapy, physiology, organic chemistry and polymer chemistry. 2. The compound of claim 1 , wherein Ris hydrogen.3. The compound of any one of the preceding claims claim 1 , wherein Ris alkyl.4. The compound of any one of the preceding claims claim 1 , wherein Ris cyclopropylmethyl.5. The compound of any one of the preceding claims claim 1 , wherein G is O and represents a double bond.6. The compound of any one of the preceding claims claim 1 , wherein Ris hydrogen.7. The compound of any one of the preceding claims claim 1 , wherein Ris selected from optionally substituted alkyl claim 1 , optionally substituted amino claim 1 , and —X-POLY.8. The compound of any one of the preceding claims claim 1 , wherein Ris optionally substituted amino.9. The compound of any one of the preceding claims claim 1 , wherein Ris amino substituted with an optionally substituted aryl or optionally substituted alkyl.10. The compound of any one of the preceding claims claim 1 , wherein Ris amino substituted with an optionally substituted phenyl.12. The compound of claim 11 , wherein q is 1.13. The compound of any one or claim 11 , wherein X is —NH—.14. The compound of any one of or claim 11 , wherein X is —O—.15. The compound of any one of to claim 11 , wherein POLY is a poly(alkylene oxide) oligomer.16. The compound of any one of to claim 11 , wherein POLY is a poly(ethylene oxide) oligomer.17. The compound of any one of to claim 11 , wherein POLY is capped with an optionally substituted alkyl.18. The compound of any one of to claim 11 , wherein POLY is capped with a methyl claim 11 , trifluoromethyl claim 11 , or methyl substituted with a carboxy group.20. The compound of claim 19 , wherein X is —O—.21. The compound of claim 19 , wherein X is —NH—.22. ...

Подробнее
Номер записи: 83
26-01-2017 дата публикации

MACROCYLIC PYRIDINE DERIVATIVES

Номер: US20170022201A1
Автор: Berthelot Didier Jean-Claude, Diels Gaston Stanislas Marcella, Meerpoel Lieven, Schoentjes Bruno, Sommen Francois Maria, Versele Matthias Luc Aime, Viellevoye Marcel, Willems Mar, Wroblowski Berthold
Принадлежит: Janssen Pharmaceutica NV

The present invention relates to substituted macrocylic pyrimidine derivatives of Formula (I) 4. The compound according to claim 1 , wherein{'sub': a', 'b', 'c, 'Xis N; Xand Xrepresent CH;'}{'sub': 1', '1-4', '2-4', '2-4', '1-4', '1-4', '1-4', '1-4', '7', '8', '2', '7', '8', '2', '9', '11', '1-4', '11', '11', '1-4', '11, 'Rrepresents hydrogen, Calkyl, Calkenyl, Calkynyl, cyanoCalkyl, —C(═O)—Calkyl, —C(═O)-haloCalkyl, haloCalkyl, —C(═O)NRR, —SO—NRR, —SO—R, R, Calkyl substituted with R, —C(═O)—R, or —C(═O)—Calkyl-R;'}{'sub': 2', '1-4', '1-4', '3-6', '1-4', '1-4', '1-4', '1-4', '1-4', '1-4', '2, 'each Rindependently represents hydrogen, Calkyl, Calkyl substituted with Ccycloalkyl, hydroxyCalkyl, CalkyloxyCalkyl, carboxyl, —C(═O)—O—Calkyl wherein Calkyl is optionally substituted with Calkyloxy, or —C(═O)—NH;'}or{'sub': 1', '2', '3-4', '3-4', '3-4', '3-4', '3', '1-4', '7', '8', '2', '7', '8', '2', '7', '8', '7', '8', '7', '8, 'Rand one Rare taken together to form Calkanediyl or Calkenediyl, each of said Calkanediyl and Calkenediyl optionally being substituted with 1 to 4 substituents each independently selected from hydroxyl, oxo, halo, cyano, N, hydroxyCalkyl, —NRR, —SO—NRR, —NH—SO—NRR, —C(═O)—NRR, or —NH—C(═O)—NRR;'}{'sub': '12', 'Ris hydrogen.'}8. The compound according to claim 1 , wherein{'sub': 1', '1-4', '2-4', '1-4', '1-4', '1-4', '1-4', '11', '11, 'Rrepresents hydrogen, Calkyl, Calkenyl, hydroxyCalkyl, CalkyloxyCalkyl, Calkyl substituted with R, or —C(═O)—R;'}{'sub': 2', '1-4', '1-4', '3-6', '1-4', '2', '1-4, 'each Rindependently represents hydrogen, Calkyl, Calkyl substituted with Ccycloalkyl, carboxyl, —C(═O)—O—Calkyl, —C(═O)—NH, —C(═O)—NH(Calkyl); or'}{'sub': 1', '2', '1-4', '2-4', '1-4', '2-4', '3', '7', '8', '2', '7', '8, 'Rand one Rare taken together to form Calkanediyl or Calkenediyl, each of said Calkanediyl and Calkenediyl optionally being substituted with 1 substituent selected from hydroxyl, oxo, halo, cyano, N, —NRR, —NH—SO—NRR.'}9. The compound ...

Подробнее
Номер записи: 84
26-01-2017 дата публикации

High-purity crystals of active blood coagulation factor x (fxa) inhibitor

Номер: US20170022220A1
Автор: Koutarou Kawanami, Yasuo Kitani
Принадлежит: Daiichi Sankyo Co Ltd

An object of the present invention is to provide a high-purity crystal of a compound represented by formula (1 a ) that is an activated blood coagulation factor X (FXa) inhibitor. Solution: High-purity crystals of a compound represented by the following formula (1 a ): wherein, with regard to the content of impurities, the maximum content of any one type of impurity is 0.03% or less, and the total content of impurities is 0.13% or less, and wherein the high-purity crystals are obtained by a step of dissolving crystals in a solvent and then recrystallizing them.

Подробнее
Номер записи: 85
26-01-2017 дата публикации

HETEROCYCLIC COMPOUND AND USE THEREOF

Номер: US20170022222A1
Автор: ASANO Yasutomi, Honda Eiji, IMAEDA Toshihiro, KORI Masakuni, Mochizuki Michiyo, Nakamura Shinji, TOYOFUKU Masashi, Ujikawa Osamu
Принадлежит:

Provided is a compound represented by the formula (I): 5. The compound according to claim 2 , wherein L is a bond claim 2 , or a salt thereof.6. The compound according to claim 2 , wherein ring D is an optionally substituted 3-8-membered monocyclic non-aromatic hydrocarbon ring claim 2 , an optionally substituted 6-14-membered aromatic hydrocarbon ring claim 2 , an optionally substituted 6-14-membered non-aromatic hydrocarbon ring claim 2 , an optionally substituted 5-6-membered monocyclic aromatic heterocycle claim 2 , an optionally substituted 3-8-membered monocyclic non-aromatic heterocycle claim 2 , an optionally substituted 8-14-membered condensed aromatic heterocycle or an optionally substituted 6-14-membered condensed non-aromatic heterocycle claim 2 , or a salt thereof.7. The compound according to claim 2 , wherein ring D is{'sub': '3-7', 'optionally substituted Ccycloalkane,'}{'sub': '6-14', 'optionally substituted Carene,'}optionally substituted dihydronaphthalene,optionally substituted tetrahydronaphthalene,optionally substituted dihydroinden,optionally substituted thiophene,optionally substituted azetidine,optionally substituted piperidine,optionally substituted furan,optionally substituted pyridine,optionally substituted pyrazole,optionally substituted 1,2,4-oxadiazole,optionally substituted dihydrobenzodioxin,optionally substituted dihydrobenzofuran,optionally substituted benzodioxole,optionally substituted benzofuran,optionally substituted indole,optionally substituted quinoline,optionally substituted benzimidazole,optionally substituted benzothiazole,optionally substituted indazole, oroptionally substituted dibenzothiophene,or a salt thereof.9. The compound according to claim 2 , wherein ring D is benzene optionally substituted by 1-3 substituents selected from(1) a halogen atom;(2) cyano;(3) hydroxy;{'sub': 1-6', '1-6', '1-6, '(4) Calkyl optionally substituted by substituent(s) selected from 1) a halogen atom, 2)phenyl optionally substituted by ...

Подробнее
Номер записи: 86
17-04-2014 дата публикации

AMINO-DIHYDROTHIAZINE AND AMINO-DIOXIDO DIHYDROTHIAZINE COMPOUNDS AS BETA-SECRETASE ANTAGONISTS AND METHODS OF USE

Номер: US20140107109A1
Автор: Allen Jennifer R., Cheng Yuan, Choquette Deborah, Epstein Oleg, Guzman-Perez Angel, Harrington Paul E., HUA Zihao, Human Jason Brooks, Hungate Randall W., Judd Ted, Lewis Richard T., Liu Qingyian, Lopez Patricia, Minatti Ana Elena, Olivieri Philip, Romero Karina, Rumfelt Shannon, Rzasa Robert M., SCHENKEL Laurie, STELLWAGEN John, White Ryan, Xue Qiufen, ZHENG Xiao, ZHONG Wenge
Принадлежит:

The present invention provides a new class of compounds useful for the modulation of beta-secretase enzyme (BACE) activity. The compounds have a general Formula I: 2. The compound according to claim 1 , or a stereoisomer or pharmaceutically acceptable salt thereof claim 1 , wherein n is 2.4. The compound according to claim 2 , or a stereoisomer or pharmaceutically acceptable salt thereof claim 2 , wherein{'sup': 4', '4, 'Ais CRor N;'}{'sup': 5', '5, 'Ais CRor N;'}{'sup': 6', '6, 'Ais CRor N;'}{'sup': 8', '8', '4', '5', '6', '8, 'Ais CRor N, provided that no more than one of A, A, Aand Ais N;'}{'sup': 1', '2, 'sub': 3', '3', '3', '3', '3', '3', '2', '2, 'each of Rand R, independently, is H, F, Cl, CF, OCF, methyl,ethyl, CN, OH, OCH, SCH, NHCH, C(O)CHor CHOCHF;'}{'sup': '3', 'sub': 1-4', '1-4', '2', '2', '2, 'Ris Calkyl, Chaloalkyl, CHOH, CHOCHFor cyclopropyl; and'}{'sup': 4', '5', '6', '8, 'sub': 3', '3', '3', '3', '3', '3, 'each of R, R, Rand R, independently, is H, F, Cl, CF, OCF, methyl, ethyl, CN, OH, OCH, SCH, NHCHor C(O)CH.'}6. The compound according to claim 2 , or a stereoisomer or pharmaceutically acceptable salt thereof claim 2 , wherein Ris —NH—C(═O)—R.7. The compound according to claim 2 , or a stereoisomer or pharmaceutically acceptable salt thereof claim 2 , wherein Ris —NH—R claim 2 , —O—Ror S—R.9. The compound according to claim 2 , or a stereoisomer or pharmaceutically acceptable salt thereof claim 2 , wherein{'sup': 4', '4, 'Ais CR;'}{'sup': 5', '5, 'Ais CR;'}{'sup': 6', '6, 'Ais CR; and'}{'sup': 8', '8', '4', '5', '6', '8, 'sub': 3', '2', '2', '3, 'Ais CR; wherein each of R, R, Rand R, independently, is H, F, CF, CFH, CHF or CH.'}11. The compound according to claim 10 , or a stereoisomer claim 10 , tautomer or pharmaceutically acceptable salt thereof claim 10 , wherein{'sup': 4', '4, 'Ais CRor N;'}{'sup': 5', '5, 'Ais CRor N;'}{'sup': 6', '6, 'Ais CRor N;'}{'sup': 8', '8', '4', '5', '6', '8, 'Ais CRor N, provided no more than one of A, A, Aand Ais ...

Подробнее
Номер записи: 87
25-01-2018 дата публикации

CONDENSED HETEROCYCLIC COMPOUNDS AND PESTICIDES

Номер: US20180022760A1
Автор: Kobayashi Masaki, KUDO Takao, MAIZURU Yukihiro, MATSUI Hiroto, NOTO Kenkichi, TANAKA Ayano
Принадлежит: NISSAN CHEMICAL INDUSTRIES, LTD.

To provide novel pesticides, especially insecticides or acaricides. 2: The condensed heterocyclic compound or its salt or an N-oxide thereof according to claim 1 , wherein:{'sub': 'n', 'sup': '1', 'D substituted with —S(O)Ris a ring represented by D1;'}{'sub': '1', 'Gis C(Y1);'}{'sub': '2', 'Gis C(Y2);'}{'sub': '3', 'Gis C(Y3);'}{'sub': '4', 'Gis C(Y4);'}{'sup': 2', '2, 'Ais C(R);'}{'sup': 3', '3, 'Ais C(R);'}{'sup': '1', 'sub': 1', '6', '1', '6', '2', '6', '2', '6', '2', '6', '2', '6', '3', '6', '1', '6', '3', '6', '1', '6, 'Ris C-Calkyl, C-Chaloalkyl, C-Calkenyl, C-Chaloalkenyl, C-Calkynyl, C-Chaloalkynyl, C-Ccycloalkyl (C-C) alkyl or C-Chalocycloalkyl (C-C) alkyl;'}{'sup': '2', 'sub': 1', '6', '1', '6, 'Ris a hydrogen atom, a halogen atom, C-Calkyl or C-Chaloalkyl;'}{'sup': 3', '3a, 'sub': 1', '6', '1', '6', '1', '8', '1', '8', '1', '6', '1', '6', '1', '6', '1', '6', '1', '6', '1', '6', '1', '6, 'Ris a hydrogen atom, a halogen atom, C-Calkyl, C-Chaloalkyl, C-Calkoxy, C-Chaloalkoxy, C-Calkylthio, C-Chaloalkylthio, (C-C) alkylthio optionally substituted with R, C-Calkylsulfinyl, C-Chaloalkylsulfinyl, C-Calkylsulfonyl or C-Chaloalkylsulfonyl;'}{'sup': 4', '4a, 'sub': 1', '6', '1', '6', '1', '8', '1', '8', '1', '6', '1', '6', '1', '6', '1', '6', '1', '6', '1', '6', '1', '6, 'Ris a hydrogen atom, a halogen atom, C-Calkyl, C-Chaloalkyl, C-Calkoxy, C-Chaloalkoxy, C-Calkylthio, C-Chaloalkylthio, (C-C) alkylthio optionally substituted with R, C-Calkylsulfinyl, C-Chaloalkylsulfinyl, C-Calkylsulfonyl or C-Chaloalkylsulfonyl;'}{'sup': 5', '6', '8, 'sub': 1', '6', '1', '6, 'each of R, Rand Ris independently a hydrogen atom, a halogen atom, C-Calkyl or C-Chaloalkyl;'}{'sup': '7', 'sub': 1', '6, 'Ris a hydrogen atom, a halogen atom or C-Chaloalkyl;'}{'sup': 1a', '1a-a', '10a, 'sub': 1', '6', '1', '6', '2', '6', '2', '6', '1', '8', '3', '6, 'Ais a hydrogen atom, C-Calkyl, (C-C) alkyl optionally substituted with A, C-Calkenyl, C-Calkynyl, C-Calkoxy, C-Ccycloalkyl or C(O)R;'}{'sup ...

Подробнее
Номер записи: 88
10-02-2022 дата публикации

COMPOUNDS AND METHODS FOR INHIBITING MITOTIC PROGRESSION

Номер: US20220041605A1
Автор: Boyce Richard J., Claiborne Christopher F., Payne Lloyd J., Sells Todd B., Stroud Stephen G., Travers Stuart, Vos Tricia J., Weatherhead Gabriel S.
Принадлежит:

This invention relates to compounds and methods for the treatment of cancer. In particular, the invention provides compounds that inhibit Aurora kinase, pharmaceutical compositions comprising the compounds, and methods of using the compounds for the treatment of cancer. 2. The compound of claim 1 , wherein:{'sup': x', 'y', '3', 'x', 'y, 'sub': '1-6', 'each of Rand Rindependently is hydrogen, fluoro, or a Caliphatic optionally substituted with one or two R; or Rand R, taken together with the carbon atom to which they are attached, form an optionally substituted 3- to 6-membered cycloaliphatic ring;'}{'sup': e', '4', '3', '7, 'sub': '1-3', 'Ris hydrogen, —OH, —NHR, —SH, or a Caliphatic optionally substituted with Ror R;'}{'sup': f1', 'f2, 'Rand Rtogether form a bond;'}{'sub': 2', '1-3', '1-3', '1-3', '2', '1-3', '1-3', '1-3, 'sup': 1', '7', '1', '7', '1', '7, 'G is —H, —OH, —NH, —O(Calkyl), —NH(Calkyl), —N(Calkyl), Calkyl, Cfluoroalkyl, —O-L-R, —N(Calkyl)-L-R, or -L-R; and'}{'sup': '1', 'sub': '1-3', 'Lis a covalent bond or Calkylene.'}5. The compound of claim 3 , wherein each of Rand Rindependently is hydrogen claim 3 , fluoro claim 3 , or a Caliphatic optionally substituted with one or two R; or Rand R claim 3 , taken together with the carbon atom to which they are attached claim 3 , form an optionally substituted 3- to 6-membered cycloaliphatic ring.6. The compound of claim 5 , wherein Ring A is a substituted or unsubstituted ring selected from the group consisting of furano claim 5 , dihydrofurano claim 5 , thieno claim 5 , dihydrothieno claim 5 , cyclopenteno claim 5 , cyclohexeno claim 5 , 2H-pyrrolo claim 5 , pyrrolo claim 5 , pyrrolino claim 5 , pyrrolidino claim 5 , oxazolo claim 5 , thiazolo claim 5 , imidazolo claim 5 , imidazolino claim 5 , imidazolidino claim 5 , pyrazolo claim 5 , pyrazolino claim 5 , pyrazolidino claim 5 , isoxazolo claim 5 , isothiazolo claim 5 , oxadiazolo claim 5 , triazolo claim 5 , thiadiazolo claim 5 , 2H-pyrano claim 5 , 4H- ...

Подробнее
Номер записи: 89
10-02-2022 дата публикации

POLYMORPHIC MIXTURE OF RIFAXIMIN AND ITS USE FOR THE PREPARATION OF SOLID FORMULATIONS

Номер: US20220041622A9
Автор: Argese Maria, Fumagalli Emanuela, Grilli Maria Donata, Grisenti Paride, Motta Giuseppe, Pengo Daniele
Принадлежит:

A Rifaximin polymorphic mixture of α/β form in a relative ratio of 85/15±3 and a process for its preparation. The polymorphic mixture of Rifaximin is for use as a medicament, in particular in the treatment of traveler's diarrhea and hepatic encephalopathy. A pharmaceutical composition comprises the polymorphic mixture of Rifaximin as active ingredient, in particular, a solid formulation, more in particular, a film coated tablet. A polymorphic form of crude wet rifaximin and of purified wet rifaximin their use are used as intermediates in a process for the preparation of Rifaximin polymorphic mixture of α/β form in a relative ratio of 85/15±3. 1. (canceled)2. A process for the preparation of a Rifaximin polymorphic mixture of α/β form in a relative ratio of 85/15±3 , said process comprising:a) reacting a molar equivalent of Rifamycin O with 2 or 3 equivalents of 2-amino-4-methylpyridine in a solvent mixture of water and ethyl alcohol in a volumetric ratio between 1:2 and 1:3, at a temperature between 20° C. and 30° C., to give a reaction mass;b) treating said reaction mass at 20-30° C. with ascorbic acid, then with a mixture of water and ethyl alcohol and concentrated aqueous hydrochloric acid, and adjusting the pH of the reaction mass to 6.0-6.5, to obtain a suspension;c) filtering the suspension to obtain a first solid, washing the first solid with a water/ethyl alcohol solvent mixture to obtain crude wet Rifaximin;d) purifying the crude wet Rifaximin by dissolving the crude wet Rifaximin in ethyl alcohol at a temperature between 50° C. and 60° C. and precipitating wet purified Rifaximin by adding water and cooling to between 28-33° C. under stirring for a period of 1-3 hours, cooling to 20-25° C. under stirring for 1-2 hours, and then cooling to 0-5° C. under stirring to obtain a precipitate of wet purified Rifaximin;e) filtering the wet purified Rifaximin to obtain a second solid and washing the second solid with water, andf) drying the second solid under ...

Подробнее
Номер записи: 90
24-01-2019 дата публикации

SUBSTITUTED TETRAHYDROCARBAZOLE AND CARBAZOLE CARBOXAMIDE COMPOUNDS

Номер: US20190023719A1
Автор: Batt Douglas G., Bertrand Myra Beaudoin, De Lucca George V., Galella Michael A., Ko Soo Sung, Langevine Charles M., Liu Qingjie, SHI Qing, Srivastava Anurag S., Tino Joseph A., Watterson Scott Hunter
Принадлежит:

Disclosed are compounds of Formula (I) 3. The compound according to wherein: Ris F or Cl.4. The compound according to wherein Ris —C(CH)OH.6. The compound according to wherein: Ris F or Cl.7. The compound according to wherein Ris —C(CH)OH.8. (canceled)9. (canceled)10. (canceled)11. (canceled)12. (canceled)13. A pharmaceutical composition comprising a compound according to and a pharmaceutically acceptable carrier. This application is a continuation application of U.S. patent application Ser. No. 15/625,417, filed Jun. 16, 2017, which is a continuation application of U.S. patent application Ser. No. 15/067,915, filed Mar. 11, 2016, which is a continuation application of U.S. patent application Ser. No. 14/314,602 filed Jun. 25, 2014, which claims priority to U.S. Provisional Application 61/839,141, filed Jun. 25, 2013, the contents of which are herein incorporated by reference in their entirety.The present invention generally relates to substituted tetrahydrocarbazole and carbazole carboxamide compounds useful as kinase inhibitors, including the modulation of Bruton's tyrosine kinase (Btk) and other Tec family kinases such as Itk. Provided herein are substituted tetrahydrocarbazole and carbazole carboxamide compounds, compositions comprising such compounds, and methods of their use. The invention further pertains to pharmaceutical compositions containing at least one compound according to the invention that are useful for the treatment of conditions related to kinase modulation and methods of inhibiting the activity of kinases, including Btk and other Tec family kinases such as Itk, in a mammal.Protein kinases, the largest family of human enzymes, encompass well over 500 proteins. Btk is a member of the Tec family of tyrosine kinases, and is a regulator of early B-cell development, as well as mature B-cell activation, signaling, and survival.B-cell signaling through the B-cell receptor (BCR) leads to a wide range of biological outputs, which in turn depend on the ...

Подробнее
Номер записи: 91
24-01-2019 дата публикации

COMPOUNDS THAT INHIBIT MCL-1 PROTEIN

Номер: US20190023720A1
Автор: Brown Sean P., GONZALEZ BUENROSTRO Ana, LI Yunxiao, LI Zhihong, LIZARZABURU Mike Elias, LUCAS Brian S, Paras Nick A., TAYGERLY Joshua, VIMOLRATANA Marc, Wang Xianghong, Yu Ming, ZANCANELLA Manuel, ZHU Liusheng
Принадлежит: Amgen Inc.

Provided herein are myeloid cell leukemia 1 protein (Mcl-1) inhibitors, methods of their preparation, related pharmaceutical compositions, and methods of using the same. For example, provided herein are compounds of Formula I, 2. The method of claim 1 , wherein the cancer is a hematological malignancy.3. The method of claim 1 , wherein the cancer is acute myelogenous leukemia.4. The method of claim 1 , wherein the cancer is multiple myeloma.5. The method of claim 1 , wherein the cancer is non-Hodgkin's lymphoma.6. The method of claim 1 , wherein the method further comprises administering to the patient a therapeutically effective amount of at least one additional pharmaceutically active compound.7. The method of claim 6 , wherein the at least one additional pharmaceutically active compound is carfilzomib.8. The method of claim 1 , wherein b is a double bond.9. The method of claim 1 , wherein R is Cl.10. The method of claim 1 , wherein Ris Calkyl.11. The method of claim 4 , wherein Ris CH.12. The method of claim 1 , wherein Ris H and Ris Calkyl.13. The method of claim 1 , wherein Ris H and Ris Calkyl.16. The method of claim 15 , wherein the cancer is a hematological malignancy.17. The method of claim 15 , wherein the cancer is acute myelogenous leukemia.18. The method of claim 15 , wherein the cancer is multiple myeloma.19. The method of claim 15 , wherein the cancer is non-Hodgkin's lymphoma.20. The method of claim 15 , wherein the method further comprises is administering to the patient a therapeutically effective amount of at least one additional pharmaceutically active compound.21. The method of claim 20 , wherein the at least one additional pharmaceutically active compound is carfilzomib.23. The method of claim 22 , wherein the cancer is a hematological malignancy.24. The method of claim 22 , wherein the cancer is acute myelogenous leukemia.25. The method of claim 22 , wherein the cancer is multiple myeloma.26. The method of claim 22 , wherein the cancer is non- ...

Подробнее
Номер записи: 92
24-04-2014 дата публикации

FILAMIN A BINDING ANTI-INFLAMMATORY AND ANALGESIC

Номер: US20140113895A1
Автор: Blasko Andrei, Burns Barbier Lindsay, Lin Nan-Horng, Wang Hoau-Yan
Принадлежит:

A compound or its pharmaceutically acceptable salt, optionally including both individual enantiomeric forms, a racemate, diastereomers and mixtures thereof, composition and method are disclosed that can provide analgesia and reduce inflammation. A contemplated compound has a structure that corresponds to Formula A, wherein the R group substituents, d, e, f, k, n, m, D, E, F, K, G, P, Q, W, and Z are defined within. 5. The compound or its pharmaceutically acceptable salt according to claim 4 , wherein X is C(O) claim 4 , CH claim 4 , CD claim 4 , or SO.6. The compound or its pharmaceutically acceptable salt according to claim 4 , wherein W is NR claim 4 , S or O.7. The compound or its pharmaceutically acceptable salt according to claim 4 , wherein circle A is selected from the group consisting of phenyl claim 4 , pyridyl claim 4 , pyrazinyl claim 4 , pyrimidinyl claim 4 , pyridazinyl claim 4 , triazinyl (1 claim 4 ,3 claim 4 ,5-triazinyl claim 4 , 1 claim 4 ,2 claim 4 ,4-triazinyl and 1 claim 4 ,2 claim 4 ,3-triazinyl) claim 4 , furanyl claim 4 , thienyl claim 4 , oxazolyl claim 4 , isoxazolyl claim 4 , thiazolyl claim 4 , isothiazolyl claim 4 , naphthyl claim 4 , benzofuranyl claim 4 , isobenzofuranyl claim 4 , benzothiophenyl claim 4 , isobenzothiophenyl claim 4 , benzoxazolyl claim 4 , benzisoxazole claim 4 , quinolyl claim 4 , isoquinolyl claim 4 , quinazolyl claim 4 , cinnolinyl claim 4 , quinoxalinyl claim 4 , naphthyridinyl claim 4 , and benzopyrimidinyl.8. The compound or its pharmaceutically acceptable salt according to claim 4 , wherein one of Q and Z is CHand the other is absent.11. The compound or its pharmaceutically acceptable salt according to claim 10 , wherein X is C(O) claim 10 , CH claim 10 , CD claim 10 , or SO.12. The compound or its pharmaceutically acceptable salt according to claim 10 , wherein W is NR claim 10 , S or O.13. The compound or its pharmaceutically acceptable salt according to claim 10 , wherein circle A is selected from the group ...

Подробнее
Номер записи: 93
29-01-2015 дата публикации

POLY (ADP-RIBOSE) POLYMERASE (PARP) INHIBITORS

Номер: US20150031652A1
Автор: Gangloff Anthony R., Jennings Andrew John, Jones Benjamin, Kiryanov Andre A.
Принадлежит: Takeda Pharmaceutical Company Limited

Disclosed are compounds of the following formula: 2. (canceled)5. The compound , tautomer or pharmaceutically acceptable salt thereof according to or , wherein each Ris independently selected from the group consisting of hydrogen , halo , and a substituted or unsubstituted (C)alkyl.7. The compound claim 6 , tautomer or pharmaceutically acceptable salt thereof according to claim 6 , wherein each Ris independently selected from the group consisting of hydrogen claim 6 , halo claim 6 , and a substituted or unsubstituted (C)alkyl.10. The compound claim 6 , tautomer or pharmaceutically acceptable salt thereof according to or claim 6 , wherein each Ris independently selected from the group consisting of hydrogen claim 6 , halo claim 6 , and a substituted or unsubstituted (C)alkyl.12. The compound claim 11 , tautomer or pharmaceutically acceptable salt thereof according to claim 11 , wherein each Ris independently selected from the group consisting of hydrogen claim 11 , halo claim 11 , and a substituted or unsubstituted (C)alkyl.13. The compound claim 11 , tautomer or pharmaceutically acceptable salt thereof according to or claim 11 , wherein Ris selected from (C)alkyl and aryl(C)alkyl claim 11 , each substituted or unsubstituted.1417-. (canceled)181417. The compound claim 11 , tautomer or pharmaceutically acceptable salt thereof according to any one of claim 11 , claim 11 , and to claim 11 , wherein Rand Rare each independently selected from hydrogen claim 11 , halo claim 11 , and substituted or unsubstituted (C)alkyl.19. The compound claim 1 , tautomer or pharmaceutically acceptable salt thereof according to any one of the preceding claim 1 , wherein X is O.20. The compound claim 1 , tautomer or pharmaceutically acceptable salt thereof according to any one of to claim 1 , wherein X is NR claim 1 , and Ris selected from the group consisting of hydrogen and a substituted or unsubstituted (C)alkyl.2122-. (canceled)23211. The compound claim 1 , tautomer or pharmaceutically ...

Подробнее
Номер записи: 94
29-01-2015 дата публикации

INHIBITORS OF BETA-SECRETASE

Номер: US20150031691A1
Автор: Cacatian Salvacion, Dillard Lawrence Wayne, Jia Lanqi, Leftheris Katerina, Morales-Ramos Angel, Singh Suresh B., VENKATRAMAN SHANKAR, Wu Guosheng, Xu Zhenrong, YUAN Jing, ZHENG Yajun
Принадлежит:

The present invention relates to compounds represented by Structural Formula (I): 2. The compound of claim 1 , wherein:{'sup': '1', 'sub': 1', '3, 'Ris a —H or a (C-C)alkyl;'}{'sup': 2', '5', '12', '13', '6', '7', 'c, 'sub': 2', '1', '6', '2', '6', '2', '6', '2', '6', '3', '8', '4', '8', '1', '6', '2', '6', '2', '6', '2', '6', '3', '8', '4', '8', '2', '1', '6', '2', '6', '1', '6', '3', '8', '1', '3', '1', '3', '1', '3', '1', '6', '2, 'each Ris independently selected from the group consisting of —H, halogen, —CN, —NO, —OR, —C(═O)NRR, (C-C)alkyl, (C-C)alkenyl, (C-C)alkynyl, phenyl(C-C)alkynyl, (C-C)cycloalkyl, (C-C)cyclohexenyl, phenyl, pyridyl, thiazolyl, pyridazinyl, pyridazinone, pyridinone, thiophenyl, pyrrolyl, pyrimidinyl, pyrazinyl, indolyl, pyrrolidinyl, piperazinyl and morpholinyl, each of the (C-C)alkyl, (C-C)alkenyl, (C-C)alkynyl, phenyl(C-C)alkynyl, (C-C)cycloalkyl, (C-C)cycloalkenyl, phenyl, pyridinyl, thiazolyl, pyridazinyl, pyridazinone, pyridinone, thiophenyl, pyrrolyl, pyrimidinyl, pyrazinyl, indolyl, pyrrolidinyl, piperazinyl and morpholinyl is optionally substituted with 1 to 3 substituents independently selected from the group consisting of halogen, —OH, —CN, —NO, (C-C)alkyl, (C-C)alkynyl, halo(C-C)alkyl, (C-C)cycloalkyl, (C-C)alkoxy, halo(C-C)alkoxy, (C-C)alkoxy(C-C)alkyl, —NRRand —SOR; and'}{'sup': 0', '6', '7', '0, 'sub': 1', '6', '1', '6', '1', '3', '3', '6, 'each R, when present, is independently selected from the group consisting of —H, halogen, —CN, (C-C)alkyl, halo(C-C)alkyl, (C-C)alkoxy and —NRR, or tow R, taken together to the carbon atom to which they are attached, form a Cto Ccycloalkyl.'}3. The compound of claim 2 , wherein:{'sup': 2', '5, 'sub': 1', '6', '2', '6', '1', '6', '2', '6', '3', '6', '1', '3', '1', '3', '1', '3', '1', '3, 'each Ris independently selected from —Br, —Cl, —CN, —OR, (C-C)alkyl, (C-C)alkynyl, phenyl and pyridinyl, wherein each of the (C-C)alkyl, (C-C)alkynyl, phenyl and pyridinyl is optionally substituted with 1 ...

Подробнее
Номер записи: 95
29-01-2015 дата публикации

ISOTHIAZOLOPYRIDINONES USEFUL FOR THE TREATMENT OF (INTER ALIA) CYSTIC FIBROSIS

Номер: US20150031720A1
Автор: Gallardo-Godoy Alejandra
Принадлежит: VERTEX PHARMACEUTICALS INCORPORATED

The present invention relates to modulators of ATP-Binding Cassette (“ABC”) transporters or fragments thereof, including Cystic Fibrosis Transmembrane Conductance Regulator, compositions thereof, and methods therewith. The present invention also relates to methods of treating ABC transporter mediated diseases using such modulators. 135-. (canceled)39. The kit of claim 38 , further comprising instructions for:a) contacting an additional composition with the biological sample;b) measuring the activity of said CFTR or a fragment thereof in the presence of said additional compound, andc) comparing the activity of the CFTR in the presence of the additional compound with the density of CFTR in the presence of a composition of formula I. The present application is a continuation of International Application No. PCT/US2008/073242 filed Aug. 15, 2008 entitled “Isothiazolopyridinones Useful for the Treatment of (Inter Alia) Cystic Fibrosis” which in turn claims the benefit under 35 U.S.C. §119, to U.S. Provisional Application No. 60/957,750, filed Aug. 24, 2007 and entitled “MODULATORS OF CYSTIC FIBROSIS TRANSMEMBRANE CONDUCTANCE REGULATOR,” the entire contents of which is incorporated herein by reference.The present invention relates to modulators of cystic fibrosis transmembrane conductance regulator (“CFTR”), compositions thereof, and methods therewith. The present invention also relates to methods of treating CFTR mediated diseases using such modulators.ABC transporters are a family of membrane transporter proteins that regulate the transport of a wide variety of pharmacological agents, potentially toxic drugs, and xenobiotics, as well as anions. ABC transporters are homologous membrane proteins that bind and use cellular adenosine triphosphate (ATP) for their specific activities. Some of these transporters were discovered as multidrug resistance proteins (like the MDR1-P glycoprotein, or the multidrug resistance protein, MRP1), defending malignant cancer cells against ...

Подробнее
Номер записи: 96
17-02-2022 дата публикации

POLYMORPHIC MIXTURE OF RIFAXIMIN AND ITS USE FOR THE PREPARATION OF SOLID FORMULATIONS

Номер: US20220048926A1
Автор: Argese Maria, Fumagalli Emanuela, Grilli Maria Donata, Grisenti Paride, Motta Giuseppe, Pengo Daniele
Принадлежит:

A Rifaximin polymorphic mixture of α/β form in a relative ratio of 85/15±3 and a process for its preparation. The polymorphic mixture of Rifaximin is for use as a medicament, in particular in the treatment of traveler's diarrhea and hepatic encephalopathy. A pharmaceutical composition comprises the polymorphic mixture of Rifaximin as active ingredient, in particular, a solid formulation, more in particular, a film coated tablet. A polymorphic form of crude wet rifaximin and of purified wet rifaximin their use are used as intermediates in a process for the preparation of Rifaximin polymorphic mixture of α/β form in a relative ratio of 85/15±3. 113-. (canceled)14. A Rifaximin polymorphic mixture of α/β form in a relative ratio of 85/15±3 , characterized by an X-Ray spectrum with characteristic 2theta values at about: 5.32 , 5.78 , 6.50 , 7.24 , 7.82 , 8.80 , 10.50 , 11.02 , 11.58 , 13.08 , 14.42 , 17.32 , 17.68 , 18.58 , 19.52 , 21.04 , 21.60 , and 21.92.15. A pharmaceutical composition comprising the polymorphic mixture of Rifaximin of and a vehicle claim 14 , excipient claim 14 , or formulative ingredient.16. The pharmaceutical composition of claim 15 , wherein the pharmaceutical composition is a solid pharmaceutical composition.17. The pharmaceutical composition of claim 16 , wherein the pharmaceutical composition is a film coated tablet.18. The pharmaceutical composition of claim 15 , wherein the pharmaceutical composition comprises 550 mg of Rifaximin α/β polymorphic mixture of 85/15±3.19. The pharmaceutical composition of claim 15 , wherein the pharmaceutical composition further comprises excipients.20. The pharmaceutical composition of claim 19 , wherein the excipients comprise cellulose microcrystalline claim 19 , sodium starch glycolate claim 19 , glyceryl palmitostearate claim 19 , hydrated silicon dioxide claim 19 , and talc.21. The pharmaceutical composition of claim 20 , wherein the pharmaceutical composition further comprises polyvinyl alcohol claim 20 , ...

Подробнее
Номер записи: 97
05-02-2015 дата публикации

ORGANIC SEMICONDUCTING COMPOUNDS FOR USE IN ORGANIC ELECTRONIC DEVICES

Номер: US20150034161A1
Автор: Hoven Corey V., Smith Braden, Tamayo Arnold B., Wood Thomas K.
Принадлежит:

Organic molecule semi-conducting chromophores containing a halogen-substituted core structure are disclosed. Such compounds can be used in organic heterojunction devices, such as organic molecule solar cells and transistors. 6. A compound of wherein Bis a substituted or unsubstituted thiophene.7. A compound of claim 6 , wherein Q is independently selected from substituted or unsubstituted thiophene claim 6 , pyrrole claim 6 , furan claim 6 , phenyl claim 6 , phosphole claim 6 , benzodithiophene claim 6 , spirofluorene claim 6 , spirothiophene claim 6 , bithiophene claim 6 , terthiophene claim 6 , thienothiophene claim 6 , dithienothiophene claim 6 , benzothiophene claim 6 , isobenzothiophene claim 6 , benzodithiophene claim 6 , cyclopentadithiophene claim 6 , silacyclopentadiene claim 6 , silacyclopentadiencbithiophene claim 6 , indole claim 6 , benzene claim 6 , naphthalene claim 6 , anthracene claim 6 , perylene claim 6 , indene claim 6 , fluorene claim 6 , pyrene claim 6 , azulene claim 6 , pyridine claim 6 , oxazole claim 6 , thiazole claim 6 , thiazine claim 6 , pyrimidine claim 6 , pyrazine claim 6 , imidazole claim 6 , benzoxazole claim 6 , benzoxadiazole claim 6 , benzothiazole claim 6 , benzimidazole claim 6 , benzofuran claim 6 , isobenzofuran claim 6 , thiadiazole claim 6 , dithienopyrrole claim 6 , dithienophosphole and carbazole 9 claim 6 ,9-RR′-9H-fluorene claim 6 , 9-R-9H-carbazole claim 6 , 3 claim 6 ,3′-RR′silylene-2 claim 6 ,2′-bithiophene claim 6 , 3 claim 6 ,3′RR′-cyclopenta[2 claim 6 ,1-b:3 claim 6 ,4-b′]-dithiophene claim 6 , where R and R′═C-Calkyl or C-Caryl.8. A compound of claim 5 , wherein Bis independently selected from substituted or unsubstituted thiophene claim 5 , pyrrole claim 5 , furan claim 5 , phenyl claim 5 , phosphole claim 5 , benzodithiophene claim 5 , spirofluorene claim 5 , spirothiophene claim 5 , bithiophene claim 5 , terthiophene claim 5 , thienothiophene claim 5 , dithienothiophene claim 5 , benzothiophene claim 5 , ...

Подробнее
Номер записи: 98
05-02-2015 дата публикации

SPIROPYRROLIDINE BETA-SECRETASE INHIBITORS FOR THE TREATMENT OF ALZHEIMER'S DISEASE

Номер: US20150038490A1
Автор: Cai Yaxian, Coburn Craig A., Du Xiaoxiang, Li Jian, LIU Kun, Peng Xuanjin, Soll Richard, Stachel Shawn J., Steele Thomas G., Wu Hao
Принадлежит: Merck Sharp & Dohme Corp.

The present invention is directed to spiropyrrolidine compounds of formula (I) which are inhibitors of the beta-secretase enzyme and that are useful in the treatment of diseases in which the beta-secretase enzyme is involved, such as Alzheimer's disease. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the treatment of such diseases in which the beta-secretase enzyme is involved. 2. (canceled)3. A compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein -Q-Y—Z— together forms the groups —N═CR—CR═CR— or —CR═CR—CR═N— claim 1 , thereby forming a fused pyridyl ring.4. A compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein{'sup': 10', '11', '10', '11, '-Q-Y—Z— together forms the groups —N═CR—CR═N— or —N═CR—N═CR—, thereby forming a fused pyrimidinyl ring.'}5. A compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein{'sup': 10', '10', '10', '10', '10', '10', '10', '10', '10', '10', '10, '-Q-Y—Z— together forms the groups —NH—CR═CR—, —S—CR═CR—, —O—CR═CR—, —N═CR—S—, —CR═CR═S— or —CR═CR—O—, thereby forming a five-membered heteroaryl ring.'}6. A compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 ,{'sup': 1', '2', '10', '11', '12', '13, 'wherein X-Xis —CRR—CRCR— and n is 0 or 1.'}7. A compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein X-Xis —NR—CRR— or —CRR—NR— and n is 1.8. A compound of any of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein X-Xis —S(═O)pR—CRR— and n is 1.9. A compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein X-Xis —CRR—O— or —O—CRR— claim 1 , and n is 1.10. A compound of claim 1 , wherein Ris selected from the group consisting of(1) hydrogen{'sub': '1-6', '(2) Calkyl,'}{'sub': '3-9', '(3) Ccycloalkyl, or'}(4) phenyl,{'sup': '1', 'claim-text': (a) halo,', '(b) ...

Подробнее
Номер записи: 99
09-02-2017 дата публикации

AN IMPROVED PROCESS FOR THE PREPARATION OF RIFAMYCIN DERIVATIVES

Номер: US20170037055A1
Автор: Boini Ambaiah, CHIGURUPATI KRISHNA PRASAD, Gilla Goverdhan, Vetukuri Vnkv Prasada Raju
Принадлежит:

The present invention relates to an improved and industrially advantageous process for the preparation of Rifaximin with high purity and yield. Particularly, the present invention relates to improved processes for the preparation of Rifaximin from Rifamycin O and S. More particularly the present invention relates to a process for the preparation of Rifaximin through 3-halorifamycin S. The present invention further relates to a novel polymorph of Rifaximin and process for its preparation. 2) An improved process for the preparation of Rifaximin according to claim 1 , wherein halogenating agents in step (a) are selected from Iodine or bromine.3) The process according to claim 1 , wherein suitable solvents used are selected from nitrile solvents such as acetonitrile claim 1 , propionitrile or alcohol solvents such as methanol claim 1 , ethanol claim 1 , n-propanol claim 1 , isopropanol claim 1 , n-butanol and t-butanol or hydrocarbon solvents such as toluene claim 1 , xylene claim 1 , or esters solvents such as ethyl acetate claim 1 , methyl acetate claim 1 , or water or mixtures thereof.4) The process according to claim 1 , wherein the base used in step (a) selected from pyridine claim 1 , dimethylaminopyridine claim 1 , 2-amino-4-methyl pyridine and acid used in step (b) are selected from HCl claim 1 , H2SO4 claim 1 , HNO3 claim 1 , and claim 1 , H3CCOOH.514)-) (canceled)15) A process for the preparation of Rifaximin according to claim 1 , wherein step (f) of purification comprising the steps of:a) providing Rifaximin in a solvent or mixture of solvents;b) heating the suspension of step (a) and stirring the solution at temperature 20-85° C.;c) optionally filtering the solution of step (b) on celite or on carbon bed;d) cooling the solution of step (c) to 30-50° C.;e) cooling the solution of step (d) further to −5-20° C.; andf) recovering the pure Rifaximin Form G.16) The process according to claim 15 , wherein the solvents used in step (a) is selected from water claim ...

Подробнее
Номер записи: 100