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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

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Мониторинг СМИ

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

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Поддерживает ввод нескольких поисковых фраз (по одной на строку). При поиске обеспечивает поддержку морфологии русского и английского языка
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Применить Всего найдено 8186. Отображено 100.
19-01-2012 дата публикации

Taspase1 inhibitors and their uses

Номер: US20120015990A1
Автор: Emily Cheng, James Hsieh
Принадлежит: Washington University in St Louis WUSTL

Provided herein are small molecule inhibitors of Taspase1 and methods of using the small molecule inhibitors of Taspase1 to treat neoplasm in subjects in need thereof.

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Номер записи: 1
08-03-2012 дата публикации

Compounds derived from muscodor fungi

Номер: US20120058058A1
Автор: John Kenneth Baird, Jonathan S. Margolis, Jorge I. Jimenez, Sarah F. Lego
Принадлежит: AgraQuest Inc

The present invention relates to novel compounds and compositions and the use of them for the control of fungal and bacterial pathogens, insect pests, acari, nematodes and other invertebrate pests including, but not limited to post-harvest and soil diseases, building mold remediation, and seed and grain sanitation.

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Номер записи: 2
28-06-2012 дата публикации

Process for the preparation of linagliptin

Номер: US20120165525A1
Автор: Emanuele Attolino, Marco Artico, Pietro Allegrini
Принадлежит: Dipharma Francis Srl

The present invention relates to processes for the preparation of 8-(3R)-3-aminopiperidinyl)-7-butyn-2-yl-3 -methyl-1-(4-methyl-quinazolin-2-ylmethyl)-3,7-dihydropurine-2,6-dione and novel intermediates useful in its synthesis.

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Номер записи: 3
26-07-2012 дата публикации

Novel Protein Kinase B Inhibitors - 060

Номер: US20120190679A1
Автор: Andrew Leach, Jeffrey James Morris, Paul David Johnson, Richard William Arthur Luke, Zbigniew Stanley Matusiak
Принадлежит: AstraZeneca AB

The invention relates to a novel group of compounds of Formula (I) or salts thereof: wherein Y, Z 1 , Z 2 , R 1 , R 4 , R 5 and n are as described in the specification, which may be useful in the treatment or prevention of a disease or medical condition mediated through protein kinase B (PKB) such as cancer. The invention also relates to pharmaceutical compositions comprising said compounds, methods of treatment of diseases mediated by PKB using said compounds and methods for preparing compounds of Formula (I).

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Номер записи: 4
27-09-2012 дата публикации

Process for the production of a pemetrexed salt

Номер: US20120245349A1
Автор: Huanghsiung Lin, Shanghong Chen
Принадлежит: Scinopharm Taiwan Ltd

A process of making a pemetrexed salt comprising: a) reacting a compound of formula II or an acid salt thereof, wherein each of R 1 and R 2 is independently a C1-C6 alkyl group, with an aqueous basic solution at a temperature of no more than 10° C. to obtain a first mixture comprising the pemetrexed salt; b) isolating the pemetrexed salt from the first mixture.

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Номер записи: 5
22-11-2012 дата публикации

Azabenzimidazoles as fatty acid synthase inhibitors

Номер: US20120295915A1
Автор: Amita M. Chaudhari, Christopher P. Laudeman, Cynthia A. Parrish, David Lee Musso, Jason Hallman
Принадлежит: Individual

Disclosed are compounds having Formula (I), wherein R 1 , R 2 , R 3 , R 4 , Ra, Rb, X, Y, m, and n are defined herein and methods of using the same.

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Номер записи: 6
22-11-2012 дата публикации

Methods of using selective chemotherapeutic agents for targeting tumor cells

Номер: US20120295927A1
Автор: Aleem Gangjee, Larry Matherly
Принадлежит: Duquesne Univ of Holy Spirit, WAYNE STATE UNIVERSITY

A method for treating cancer tumors, particularly ovarian cancer tumors, is described, where fused cyclic pyrimidine having a cancer treating ability is selectively delivered to an FR expressing cancerous tumor.

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Номер записи: 7
21-03-2013 дата публикации

6,8-DISUBSTITUTED PURINE COMPOSITIONS

Номер: US20130072506A1
Автор: Hanus Jan, Spichal Lukas, Strnad Miroslav, Voller Jiri, ZAHAJSKA Lenka
Принадлежит:

6,8-Disubstituted purines which can be used in drug and cosmetic compositions and/or applications are provided. These 6,8-disubstituted purines have a wide range of biological activities, including for example anti-inflammatory, anti-senescent, as well as well as other activities which are especially useful in pharmaceutical and cosmetic applications. The 6,8-disubstituted purine compounds and compositions containing such 6,8-disubstituted purines provide growth-regulatory, differentiating, antisenescent and antiaging properties with improved selectivities and efficiencies and lower toxicities than analogues known heretofore. 2. The 6 claim 1 ,8-disubstituted purines of claim 1 , wherein Ris selected from the group consisting of furfuryl claim 1 , phenyl claim 1 , benzyl claim 1 , 3-methylbut-2-en-1-yl claim 1 , cyclohexylmethyl claim 1 , allyl claim 1 , and 3 claim 1 ,3-dimethylallyl claim 1 , wherein the selected Rcan be unsubstituted or substituted with one or more halogen claim 1 , hydroxy claim 1 , methoxy claim 1 , methyl claim 1 , amino claim 1 , nitro or combinations thereof.3. The 6 claim 1 ,8-disubstituted purines of claim 1 , wherein R8 is selected from the group consisting of amino claim 1 , hydroxy claim 1 , chloro claim 1 , fluoro claim 1 , bromo claim 1 , amino(C-Calkyl)amino claim 1 , hydroxy(C-Calkyl)amino claim 1 , NHOH claim 1 , NHNH claim 1 , carboxyl claim 1 , nitro claim 1 , sulphanyl claim 1 , methylsulphanyl claim 1 , and methoxy.4. The 6 claim 3 ,8-disubstituted purines of claim 3 , wherein R8 is amino.5. The 6 claim 1 ,8-disubstituted purines of claim 1 , wherein the 6 claim 1 ,8-disubstituted purines are 6-furfurylamino-8-(amino claim 1 , hydroxy claim 1 , chloro claim 1 , fluoro claim 1 , bromo claim 1 , amino(C-Calkyl)amino claim 1 , hydroxy(C-Calkyl)amino claim 1 , NHOH claim 1 , NHNH claim 1 , carboxyl claim 1 , nitro claim 1 , sulphanyl claim 1 , methylsulphanyl claim 1 , methoxy)purine claim 1 , 6-(3-hydroxybenzylamino)-8-(amino ...

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Номер записи: 8
28-03-2013 дата публикации

PURINONE DERIVATIVE

Номер: US20130079327A1
Автор: YAMAMOTO Shingo, Yoshizawa Toshio
Принадлежит:

Compounds represented by general formula (I) (all of the symbols in the formula conform to the definitions in the Description) are compounds that, in addition to having a Btk-selective inhibitory activity, exhibit an excellent metabolic stability and can avoid hepatotoxicity or the like, and as a consequence can provide safe therapeutic agents for diseases in which B cells or mast cells participate. 2. The compound according to claim 1 , wherein Ris a Calkenyl group or a Calkynyl group claim 1 , each of which may be substituted by from one to five substituents each independently selected from the group consisting of (1) NRR claim 1 , (2) halogen atoms claim 1 , (3) CONRR claim 1 , (4) COR claim 1 , and (5) OR.3. The compound according to claim 1 , wherein ring1 is a benzene claim 1 , cyclohexane claim 1 , or pyridine ring claim 1 , each of which may be substituted by from one to five substituents each independently selected from the group consisting of (1) halogen atoms claim 1 , (2) Calkyl groups claim 1 , (3) Calkoxy groups claim 1 , (4) nitrile claim 1 , and (5) CF.4. The compound according to claim 1 , wherein ring2 is a 4- to 7-membered nitrogenous saturated heterocycle claim 1 , which may be substituted by from one to three —K—R.5. The compound according to claim 4 , wherein the 4- to 7-membered nitrogenous saturated heterocycle is an azetidine claim 4 , pyrrolidine claim 4 , or piperidine ring.7. The compound according to claim 6 , wherein Ris a Calkenyl group or a Calkynyl group claim 6 , each of which may be substituted by from one to five substituents each independently selected from the group consisting of (1) NRR claim 6 , (2) halogen atoms claim 6 , (3) CONRR claim 6 , (4) COR claim 6 , and (5) OR.8. The compound according to claim 1 , which is (1) 9-(1-acryloyl-3-azetidinyl)-6-amino-7-(4-phenoxyphenyl)-7 claim 1 ,9-dihydro-8H-purin-8-one claim 1 , (2) 6-amino-9-{(3R)-1-[(2E)-4-(dimethylamino)-2-butenoyl]-3-pyrrolidinyl}-7-(4-phenoxyphenyl)-7 claim 1 ,9 ...

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Номер записи: 9
28-03-2013 дата публикации

PYRIMIDINE SUBSTITUTED PURINE DERIVATIVES

Номер: US20130079512A1
Автор: Nagaraj Harish K., Williams Meredith
Принадлежит: Verastem

The present invention relates to purine compounds that are useful as kinase inhibitors. More particularly, the present invention relates to purine compounds, methods for their preparation, pharmaceutical compositions containing these compounds and uses of these compounds in the treatment of proliferative conditions or disorders. These compounds may be useful as medicaments for the treatment of a number of proliferative conditions or disorders including tumours and cancers as well as other disorders or conditions related to or associated with PI3 and/or mTOR kinases. 1. (canceled)3. The method of claim 2 , wherein the addition of the morpholine of Formula (III) is performed at elevated temperature.4. The method of claim 2 , wherein the reaction of the compound of Formula (II) and the morpholine of Formula (III) is performed in the presence of a solvent.5. The method of claim 4 , wherein the solvent is dimethyl acetamide claim 4 , DMF claim 4 , or THF.6. The method of claim 2 , wherein the reaction of the compound of Formula (II) and the morpholine of Formula (III) is performed in the presence of microwave irradiation.9. The method of claim 8 , wherein the activated compound of Formula Z—X—Ris an alkyl halide claim 8 , arylalkyl halide claim 8 , or heteroaryl alkyl halide.10. The method of claim 9 , wherein the alkyl halide is an alkyl bromide.11. The method of claim 9 , wherein the arylalkyl halide is a benzyl halide.12. The method of claim 8 , wherein the reaction of the compound of Formula (VI) and the activated compound of Formula Z—X—Ris performed in the presence of a base.13. The method of claim 12 , wherein the base is potassium carbonate.14. The method of claim 8 , wherein the activated compound of Formula Z—X—Ris an activated alcohol.15. The method of claim 14 , wherein the alkylation of the compound of Formula (VI) and the activated alcohol is performed in the presence of a phosphine.16. The method of claim 14 , wherein the reaction of the compound of ...

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Номер записи: 10
18-04-2013 дата публикации

IMIDAZOPYRIDINE COMPOUNDS, COMPOSITIONS AND METHODS OF USE

Номер: US20130096104A1
Автор: Lai Yingjie, Liang Jun, Magnuson Steven R., Robarge Kirk D., Tsui Vickie H., Zhang Birong, Zhou Aihe
Принадлежит: Genentech, Inc.

The invention provides compounds of Formulas Ia-Ib, stereoisomers or pharmaceutically acceptable salts thereof, wherein A, X, R, R, R, Rand Rare defined herein, a pharmaceutical composition that includes a compound of Formulas Ia-Ib and a pharmaceutically acceptable carrier, adjuvant or vehicle, and methods of using the compound or composition in therapy, as an inhibitor of TYK2 kinase and conditions related, such as inflammatory illnesses, inflammatory bowel disease or psoriasis. 2. The compound of claim 1 , wherein A is CRand X is CR.3. The compound of claim 1 , wherein A is CRand X is N.43. The compound of any one of - claims 1 , wherein Ris independently hydrogen claims 1 , halogen claims 1 , C-Calkyl claims 1 , —CF claims 1 , —OR claims 1 , —SR claims 1 , —OCF claims 1 , —NOor —NRR claims 1 , wherein both Rcannot be hydrogen at the same time claims 1 , and wherein said alkyl is optionally substituted by halogen claims 1 , ORor —NRR.53. The compound of any one of - claims 1 , wherein one Ris halogen and the other Ris hydrogen claims 1 , halogen claims 1 , C-Calkyl claims 1 , C-Ccycloalkyl claims 1 , —CF claims 1 , —OH claims 1 , —O(C-Calkyl) claims 1 , —SH claims 1 , —S(C-Calkyl) claims 1 , —OCF claims 1 , —CN claims 1 , —NO claims 1 , —NHSOCH claims 1 , —NHC(O)Ror —NRR claims 1 , wherein said alkyl and cycloalkyl are optionally substituted by halogen claims 1 , OR claims 1 , —NRRor phenyl.65. The compound of any one of - claims 1 , wherein Ris independently hydrogen claims 1 , halogen or C-Calkyl optionally substituted by R. In certain embodiments claims 1 , Ris independently F claims 1 , Cl claims 1 , Br claims 1 , —CHOH claims 1 , —CHNHor —CHmorpholinyl.76. The compound of any one of - claims 1 , wherein A is CRand Ris hydrogen claims 1 , C-Calkyl claims 1 , C-Calkenyl claims 1 , C-Calkynyl claims 1 , halogen claims 1 , —(C-Calkyl)CN claims 1 , —(C-Calkyl)OR claims 1 , —(C-Calkyl)SR claims 1 , —(C-Calkyl)NRR claims 1 , —(C-Calkyl)C(O)NRR claims 1 , —(C-Calkyl ...

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Номер записи: 11
18-04-2013 дата публикации

HETEROCYCLIC COMPOUNDS AND THEIR USES

Номер: US20130096134A1
Автор: Duquette Jason A., Lucas Brian
Принадлежит: Amgen Inc.

Substituted bicyclic heteroaryls and compositions containing them, for the treatment of general inflammation, arthritis, rheumatic diseases, osteoarthritis, inflammatory bowel disorders, inflammatory eye disorders, inflammatory or unstable bladder disorders, psoriasis, skin complaints with inflammatory components, chronic inflammatory conditions, including but not restricted to autoimmune diseases such as systemic lupus erythematosis (SLE), myestenia gravis, rheumatoid arthritis, acute disseminated encephalomyelitis, idiopathic thrombocytopenic purpura, multiples sclerosis, Sjoegren's syndrome and autoimmune hemolytic anemia, allergic conditions including all forms of hypersensitivity, The present invention also enables methods for treating cancers that are mediated, dependent on or associated with pi 105 activity, including but not restricted to leukemias, such as Acute Myeloid leukaemia (AML) Myelodysplastic syndrome (MDS) myelo-proliferative diseases (MPD) Chronic Myeloid Leukemia (CML) T-cell Acute Lymphoblastic leukaemia (T-ALL) B-cell Acute Lymphoblastic leukaemia (B-ALL) Non Hodgkins Lymphoma (NHL) B-cell lymphoma and solid tumors, such as breast cancer. 2. A method of treating rheumatoid arthritis claim 1 , ankylosing spondylitis claim 1 , osteoarthritis claim 1 , psoriatic arthritis claim 1 , psoriasis claim 1 , inflammatory diseases and autoimmune diseases claim 1 , inflammatory bowel disorders claim 1 , inflammatory eye disorders claim 1 , inflammatory or unstable bladder disorders claim 1 , skin complaints with inflammatory components claim 1 , chronic inflammatory conditions claim 1 , autoimmune diseases claim 1 , systemic lupus erythematosis (SLE) claim 1 , myestenia gravis claim 1 , rheumatoid arthritis claim 1 , acute disseminated encephalomyelitis claim 1 , idiopathic thrombocytopenic purpura claim 1 , multiples sclerosis claim 1 , Sjoegren's syndrome and autoimmune hemolytic anemia claim 1 , allergic conditions and hypersensitivity claim 1 , ...

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Номер записи: 12
09-05-2013 дата публикации

QUINAZOLINONES AS INHIBITORS OF HUMAN PHOSPHATIDYLINOSITOL 3-KINASE DELTA

Номер: US20130116266A1
Автор: FOWLER Kerry W., HUANG Danwen, KESICKI Edward A., OLIVER Amy, OOI Hua Chee, PURI Kamal Deep, Ruan Fuqiang, TREIBERG Jennifer
Принадлежит: ICOS CORPORATION

Compounds that inhibit P13Kδ activity, including compounds that selectively inhibit P13Kδ activity, are disclosed. Methods of inhibiting phosphatidylinositol 3-kinase delta isoform (P13Kδ) activity, and methods of treating diseases, such as disorders of immunity and inflammation in which P13Kδ plays a role in leukocyte function, using the compounds also are disclosed. 2. The compound according to claim 1 , wherein the compound is the S-enantiomer or a pharmaceutically acceptable salt thereof.3. A pharmaceutical composition comprising a compound according to and at least one pharmaceutically acceptable excipient.4. The pharmaceutical composition of claim 3 , wherein the compound is the S-enantiomer or a pharmaceutically acceptable salt thereof.5. A kit for use in the treatment of a medical condition comprising the compound according to .6. The kit according to claim 5 , wherein the compound is the S-enantiomer or a pharmaceutically acceptable salt thereof. This application is a continuation of U.S. application Ser. No. 12/732,124, filed Mar. 25, 2010; which is a continuation of U.S. application Ser. No. 11/596,092, filed Dec. 14, 2007, now U.S. Pat. No. 7,932,260; which is a U.S. National Phase Application of International Application No. PCT/US2005/016778, filed May 12, 2005; which claims the benefit of U.S. Provisional Patent Application No. 60/570,784, filed May 13, 2004; the entire disclosure of each of which is incorporated herein by reference.The present invention relates generally to phosphatidylinositol 3-kinase (PI3K) enzymes, and more particularly to selective inhibitors of PI3K activity and methods of using such inhibitors.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 (see Rameh et al., 274:8347-8350 (1999) for a review). The enzyme responsible for generating these phosphorylated signaling products is ...

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Номер записи: 13
16-05-2013 дата публикации

A2B ADENOSINE RECEPTOR ANTAGONISTS

Номер: US20130123280A1
Автор: Elzein Elfatih, Ibrahim Prabha N., Kalla Rao V., Li Xiaofen, Palle Venkata, Perry Thao, Varkhedkar Vaibhav, Xiao Dengming, Zablocki Jeff
Принадлежит: Gilead Sciences, Inc.

Disclosed are novel compounds that are Aadenosine receptor antagonists, useful for treating various disease states, including asthma and diarrhea. 2. The method of claim 1 , wherein the disease state is chosen from atherosclerosis claim 1 , and angiogenesis.39.-. (canceled)10. A method of treating a cardiovascular disease by inhibition of an adenosine receptor characterized as A claim 1 , comprising administering to a human in need thereof a therapeutically effective dose of the compound 3-ethyl-1-propyl-8-{1-[(3-trifluoromethylphenyl)methyl]pyrazol-4-yl}-1 claim 1 ,3 claim 1 ,7-trihydropurine-2 claim 1 ,6-dione.11. The method of claim 1 , wherein the disease state is chosen from atherosclerosis claim 1 , and angiogenesis.1218.-. (canceled) This application is a Continuation of U.S. patent application Ser. No. 11/950,740, filed Dec. 5, 2007, which is a Divisional of U.S. patent application Ser. No. 11/189,202, filed Jul. 25, 2005, now U.S. Pat. No. 7,317,017, which is a Continuation of U.S. patent application Ser. No. 10/431,167, filed May 6, 2003, now U.S. Pat. No. 6,977,300, which is a Continuation in Part of U.S. Non-Provisional patent application Ser. No. 10/290,921, filed Nov. 8, 2002, now U.S. Pat. No. 6,825,349, which claims the benefit of U.S. Provisional Patent Application Ser. No. 60/401,408, filed Aug. 5, 2002 and U.S. Provisional Patent Application Ser. No. 60/348,222, filed Nov. 9, 2001 the complete disclosure of which is hereby incorporated by reference.The present invention relates to Aadenosine receptor antagonists, and to their use in treating mammals for various disease states, such as gastrointestinal disorders, immunological disorders, neurological disorders, and cardiovascular diseases due to both cellular hyperproliferation and apoptosis, and the like. The invention also relates to methods for the preparation of such compounds, and to pharmaceutical compositions containing them.Adenosine is a naturally occurring nucleoside, which exerts its ...

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Номер записи: 14
16-05-2013 дата публикации

SOLID STATE FORMS OF LINAGLIPTIN

Номер: US20130123282A1
Автор: Burstein Revital, Erlich Motti, Metsger Leonid, Mitteman Ariel, Yurkovsky Slavik
Принадлежит:

The present invention provides solid state forms of Linagliptin, processes for preparing the solid state forms, and pharmaceutical compositions thereof. 1. Crystalline Form X of Linagliptin , characterized by data selected from: a powder XRD pattern having peaks at 8.3° , 9.6° , 13.0° , 17.6° , and 18.9°±0.2 degrees 2θ; a powder XRD pattern as shown in ; and any combinations thereof.2. The crystalline Form X according to claim 1 , characterized by a powder XRD pattern having peaks at 8.3° claim 1 , 9.6° claim 1 , 13.0° claim 1 , 17.6° claim 1 , and 18.9°±0.2 degrees 2θ claim 1 , further characterized by one claim 1 , two claim 1 , three claim 1 , four claim 1 , or five peaks selected from 8.8° claim 1 , 10.6 13.6° claim 1 , 16.2° claim 1 , and 17.0°±0.2 degrees 2θ.3. The crystalline Form X of any one of and claim 1 , which is anhydrous.4. The crystalline Form X of any one of to claim 1 , which is non-hygroscopic.5. Crystalline Form XXII of Linagliptin claim 1 , characterized by data selected from: a powder XRD pattern having peaks at 9.8° claim 1 , 10.6° claim 1 , 12.3° claim 1 , 20.1° claim 1 , and 23.7°±0.2 degrees 2θ; a powder XRD pattern as shown in ; and any combinations thereof.6. The crystalline Form XXII according to claim 5 , characterized by a powder XRD pattern having peaks at 9.8° claim 5 , 10.6° claim 5 , 12.3° claim 5 , 20.1° claim 5 , and 23.7°±0.2 degrees 2θ claim 5 , and further characterized by one or more powder XRD peaks selected from 7.1° claim 5 , 14.1° claim 5 , 15.7° claim 5 , 21.8° claim 5 , and 27.2°±0.2 degrees 2θ.7. The crystalline Form XXII of any one of and claim 5 , having a total solvent content of about 5000 ppm to about 20 ppm claim 5 , as measured by GC.8. The crystalline Form XXII of any one of to claim 5 , which is non-hygroscopic.98. The use of the solid state forms of Linagliptin according to any one of to for the preparation of a different solid state form of Linagliptin.108. The use of the solid state forms of Linagliptin ...

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Номер записи: 15
16-05-2013 дата публикации

METHODS AND COMPOSTIONS FOR TREATING PAIN

Номер: US20130123283A1
Автор: Chong Jayhong A., Fanger Christopher, McNamara Colleen, Mendel-Brehm Josh, Moran Magdalene M., Zhen Xiaoguang
Принадлежит:

The present application relates to compounds and methods for treating pain, incontinence and other conditions. 186-. (canceled) This application is a continuation of U.S. patent application Ser. No. 12/688,241, allowed, which is a divisional of and claims priority under 35 U.S.C. §121 to U.S. patent application Ser. No. 11/645,307, now U.S. Pat. No. 7,671,061, filed on Dec. 22, 2006, which is a non-provisional application of and which claims priority under 35 U.S.C. §119 to U.S. patent application Ser. No. 60/753,665, filed on Dec. 22, 2005 and U.S. patent application Ser. No. 60/817,892, filed on Jun. 29, 2006. The specifications of each of the foregoing applications are hereby incorporated by reference in their entirety.A variety of ion channel proteins exist to mediate ion flux across cellular membranes. The proper expression and function of ion channel proteins is essential for the maintenance of cell function, intracellular communication, and the like. Numerous diseases are the result of misregulation of membrane potential or aberrant calcium handling. Given the central importance of ion channels in modulating membrane potential and ion flux in cells, identification of agents that can promote or inhibit particular ion channels are of great interest as research tools and as possible therapeutic agents.One such channel is the Transient Receptor Potential A1 (TRPA1) channel (ANKTM1). TRPA1 is a calcium permeable channel, specifically a non-selective calcium permeable cation channel. In addition to calcium ions, TRPA1 channels are permeable to other cations, for example sodium. Thus, TRPA1 channels modulate membrane potential by modulating the flux of cations such as calcium and sodium ions. Although non-selective cation channels such as TRPA1 modulate, among other things, calcium ion flux, they are mechanistically distinct from voltage-gated calcium channels. Generally, voltage-gated calcium channels respond to depolarization of the potential difference across the ...

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Номер записи: 16
23-05-2013 дата публикации

SUBSTITUTED 6-(ALKYLBENZYLAMINO) PURINE DERIVATIVES FOR USE AS CYTOKININ RECEPTOR ANTAGONISTS AND PREPARATIONS CONTAINING THESE DERIVATIVES

Номер: US20130130906A1
Автор: Dolezal Karel, POPA IGOR, Schmulling Thomas, Spichal Lukas, Strnad Miroslav, Voller Jiri, Werner Tomàs
Принадлежит:

6-(alkylbenzylamino)purine derivatives of the general formula I for use as cytokinin receptor antagonists. R1 is selected from a group which includes, but is not limited to, hydroxyl, amino, nitro, thio and alkyl group. R2 denotes one to four alkyl groups. The invention also relates to preparations containing these derivatives and methods of using the derivatives. 4. A method of claim 1 , wherein the substituted 6-(alkylbenzylamino)purine derivatives are selected from the group consisting of 6-(2-amino-3-methylbenzylamino)purine claim 1 , 6-(2-amino-4-methylbenzylamino)purine claim 1 , 6-(2-amino-5-methylbenzylamino)purine claim 1 , 6-(2-amino-3-ethylbenzylamino)purine claim 1 , 6-(2-amino-5-ethylbenzylamino)purine claim 1 , 6-(2-amino-3-isopropylbenzylamino)purine claim 1 , 6-(2-amino-5-isopropylbenzylamino)purine claim 1 , 6-(2-hydroxy-3-methylbenzylamino)purine claim 1 , 6-(2-hydroxy-4-methylbenzylamino)purine claim 1 , 6-(2-hydroxy-5-methylbenzylamino)purine claim 1 , 6-(2-hydroxy-6-methylbenzylamino)purine claim 1 , 6-(2-hydroxy-3-ethylbenzylamino)purine claim 1 , 6-(2-hydroxy-4-ethylbenzylamino)purine claim 1 , 6-(2-hydroxy-5-ethylbenzylamino)purine claim 1 , 6-(2-hydroxy-6-ethylbenzylamino)purine claim 1 , 6-(2-hydroxy-3-isopropylbenzylamino)purine claim 1 , 6-(2-hydroxy-5-isopropylbenzylamino)purine claim 1 , 6-(2-nitro-3-methylbenzylamino)purine claim 1 , 6-(2-nitro-4-methylbenzylamino)purine claim 1 , 6-(2-thio-3-methylbenzylamino)purine claim 1 , 6-(2-thio-5-methylbenzylamino)purine claim 1 , 6-(2-thio-3-ethylbenzylamino)purine 6-(2-hydroxy-3 claim 1 ,5-dimethylbenzylamino)purine claim 1 , 6-(2-hydroxy-3 claim 1 ,4-dimethylbenzylamino)purine claim 1 , 6-(2-hydroxy-3 claim 1 ,6-dimethylbenzylamino)purine claim 1 , 6-(2-hydroxy-3 claim 1 ,4 claim 1 ,5-trimethylbenzylamino)purine claim 1 , 6-(2-amino-3 claim 1 ,5-dimethylbenzylamino)purine claim 1 , 6-(2-amino-3 claim 1 ,6-dimethylbenzylamino)purine claim 1 , 6-(2-hydroxy-3 claim 1 ,5-diethylbenzylamino) ...

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Номер записи: 17
30-05-2013 дата публикации

NOVEL MODULATORS OF NRF2 AND USES THEREOF

Номер: US20130137694A1
Автор: BATIST Gérald, WU Jian Hui
Принадлежит:

There is provided modulators of Nrf2 protein which comprises a compound which binds at least one of the BTB domain, IVR domain and Kelch domain of Keap1 protein, activating or inhibiting Nrf2. There is also provided pharmaceutical compositions containing the modulators, as well as uses and method of use of the modulators for the treatment of conditions. 1214.-. (canceled)15. A pharmaceutical composition comprising a therapeutically effective amount of a compound of formula (I) claim 1 , (II) claim 1 , (III) claim 1 , (IV) or (V) according to claim 1 , in association with a pharmaceutically acceptable carrier.16. The pharmaceutical composition as claimed in for neuroprotection.17. The pharmaceutical composition as claimed in for the inhibition or the activation of a Nrf2 protein.18. The pharmaceutical composition as claimed in for overcoming drug resistance in cancer chemotherapy.1926.-. (canceled)27. A method for preventing or treating a disease which involves the abnormal activation and or expression level of a Nrf2 protein in a patient in need thereof claim 1 , and/or the abnormal inhibition of a Nrf2 protein claim 1 , the method comprising administering a therapeutically effective amount of a compound of formula (I) claim 1 , (II) claim 1 , (III) claim 1 , (IV) or (V) as defined in .28. (canceled)29. The method according to claim 27 , wherein said disease is an oxidative stress associated disease chosen from Parkinson's disease claim 27 , Parkinson's disease with dementia with Lewy body claim 27 , Huntington's disease claim 27 , multiple system atrophy (MSA) claim 27 , progressive supranuclear palsy (PSA) claim 27 , corticobasal degeneration (CBD) claim 27 , frontotemporal lobe degeneration claim 27 , atherosclerosis claim 27 , heart failure claim 27 , myocardial infarction claim 27 , Alzheimer's disease claim 27 , Fragile X syndrome claim 27 , and chronic fatigue.30. (canceled)31. The method of claim 27 , wherein said disease is a cancer.32. (canceled)33. The ...

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Номер записи: 18
06-06-2013 дата публикации

COMPOSITIONS AND METHODS OF TREATING A PROLIFERATIVE DISEASE WITH A QUINAZOLINONE DERIVATIVE

Номер: US20130143902A1
Автор: EVARTS Jerry B., Lannutti Brian, WEBB Heather
Принадлежит: Gilead Calistoga LLC

Provided are methods that relate to a novel therapeutic strategy for the treatment of cancers. In particular, the method comprises administration of Compound A, 2. The compound according to or a pharmaceutically acceptable salt thereof claim 1 , wherein the compound or a pharmaceutically acceptable salt thereof is the (S)-enantiomer.3. A composition comprising the compound according to or a pharmaceutically acceptable salt thereof claim 1 , and at least one pharmaceutically acceptable excipient.4. The composition according to claim 3 , wherein the composition comprises the (S)-enantiomer of the compound or a pharmaceutically acceptable salt thereof claim 3 ,wherein the (S)-enantiomer of the compound or a pharmaceutically acceptable salt thereof is present in excess of the (R)-enantiomer of the compound or a pharmaceutically acceptable salt thereof.5. The composition according to claim 4 , wherein the composition is substantially free of the (R)-enantiomer of the compound or a pharmaceutically acceptable salt thereof.6. A method of treating a condition in a patient claim 1 , wherein the condition is cancer claim 1 , comprising administering to the patient a composition comprising the compound according to and at least one pharmaceutically acceptable excipient.7. The method according to claim 6 , wherein the composition comprises the (S)-enantiomer of the compound or a pharmaceutically acceptable salt thereof claim 6 ,wherein the (S)-enantiomer of the compound or a pharmaceutically acceptable salt thereof is present in excess of the (R)-enantiomer of the compound or a pharmaceutically acceptable salt thereof.8. The method according to claim 7 , wherein the composition is substantially free of the (R)-enantiomer of the compound or a pharmaceutically acceptable salt thereof.9. The method according to claim 7 , wherein the (S)-enantiomer of the compound or a pharmaceutically acceptable salt thereof predominates over the (R)-enantiomer of the compound or a ...

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Номер записи: 19
27-06-2013 дата публикации

IMIDAZOPYRIDINE, IMIDAZOPYRIMIDINE AND IMIDAZOPYRAZINE DERIVATIVES AS MELANOCORTIN-4 RECEPTOR MODULATORS

Номер: US20130165426A1
Автор: Bouvier Michel, Chantigny Yves, Marinier Anne, René Patricia, Ruel Rejean
Принадлежит: UNIVERSITE DE MONTREAL

Disclosed is a compound of Formula I or a salt thereof, in which X, X1, X2, R1, R2, and R3 are described herein. Also disclosed are pharmaceutical compositions and methods of using the compounds of Formula I to treat disorders mediated by melanocortin-4 receptors. 2. The compound according to claim 1 ,{'sup': 1', '2, 'wherein X is N, and Xand Xare both CH.'}3. The compound according to claim 2 , in which:{'sup': '1', 'claim-text': [{'sub': 1', '6, '1) C-Calkyl,'}, '2) aryl,', '3) heteroaryl,', {'sup': '4', '4) NHR,'}, {'sup': '4', '5) OR,'}, {'sup': '4', '6) SR, or'}, '7) heterocyclyl,, 'Ris'}{'sup': '10', 'wherein the heterocyclyl is substituted with one or more Rsubstituents;'}{'sup': '2', 'claim-text': [{'sub': 1', '6, '1) C-Calkyl-heterocyclyl,'}, {'sub': 1', '6', '1', '6', '2, '2) C-Calkyl-N(C-Calkyl), or'}, '3) heterocyclyl,, 'Ris'}{'sub': 1', '6', '1', '6, 'wherein the heterocyclyl is optionally substituted with one or more C-Calkyl substituents or C-Calkyl-aryl;'}{'sup': '3', 'claim-text': [{'sup': 5', '6, '1) C(O)NRR,'}, {'sub': '2', 'sup': 5', '6, '2) CHNRR, or'}, '3) C(O)-heterocyclyl, 'Ris'}{'sup': '10', 'wherein the heterocyclyl is optionally substituted with one or more Rsubstituents;'}{'sup': '4', 'claim-text': 1) H,', '2) aryl,', '3) heteroaryl,', {'sub': 1', '6, '4) C-Calkyl,'}, {'sub': 1', '6, '5) C-Calkyl-aryl,'}, '6) C(O)-aryl,', {'sub': 2', '6, '7) C-Calkenyl,'}, {'sub': 3', '7, '8) C-Ccycloalkyl, or'}, {'sub': 1', '6, '9) C(O)O C-Calkyl,'}], 'Ris'}{'sup': '10', 'wherein the aryl is optionally substituted with one or more Rsubstituents;'}{'sup': 5', '6, 'claim-text': [{'sub': 1', '6, '1) C-Calkyl,'}, {'sub': 1', '6', '3', '7, '2) C-Calkyl-C-Ccycloalkyl,'}, {'sub': 1', '6', '1', '6, '3) C-Calkyl-O—C-Calkyl, or'}, {'sub': 1', '6, '4) C-Calkyl-CN; and'}], 'Rand Rare each independently selected from'}{'sup': '10', 'claim-text': 1) CN,', '2) halogen,', {'sub': 1', '6, '3) C-Calkyl,'}, {'sub': 1', '6, '4) OC-Calkyl,'}, '5) C(O)OH,', {'sub': 1', '6, '6 ...

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Номер записи: 20
27-06-2013 дата публикации

XANTHINE DERIVATIVES, THE PREPARATION THEREOF AND THEIR USE AS PHARMACEUTICAL COMPOSITIONS

Номер: US20130165428A1
Автор: ECKHARDT Matthias, Himmelsbach Frank, LANGKOPF Elke, LOTZ Ralf R.H., MAIER Roland, MARK Michael
Принадлежит: Boehringer Ingelheim Pharma GmbH & Co. KG

The present invention relates to substituted xanthines of general formula 2. The compound according to claim 1 , wherein{'sup': '1', 'claim-text': A. a hydrogen atom,', {'sub': '1-6', 'B. a C-alkyl group,'}, {'sub': '3-6', 'C. a C-alkenyl group,'}, {'sub': 3-4', '1-2, 'D. a C-alkenyl group which is substituted by a C-alkyloxy-carbonyl group,'}, {'sub': '3-6', 'E. a C-alkynyl group,'}, {'sub': 3-6', '1-3, 'F. a C-cycloalkyl-C-alkyl group,'}, 'G. a phenyl group which may be substituted by a fluorine, chlorine or bromine atom or by a methyl, trifluoromethyl, hydroxy or methoxy group,', {'sub': '1-4', 'sup': 10', '12, 'claim-text': [{'sup': '10', 'claim-text': a. a hydrogen atom, a fluorine, chlorine or bromine atom,', {'sub': 1-4', '3-6, 'b. a C-alkyl, trifluoromethyl, hydroxymethyl, C-cycloalkyl, ethynyl or phenyl group,'}, {'sub': 1-4', '1-2', '1-2', '1-3', '1-3', '1-3', '1-3', '1-2', '1-3', '1-2', '1-3', '1-3', '1-3', '1-3', '3-6', '3-6', '1-2, 'c. a hydroxy, C-alkyloxy, difluoromethoxy, trifluoromethoxy, 2,2,2-trifluoroethoxy, phenoxy, benzyloxy, 2-propen-1-yloxy, 2-propyn-1-yloxy, cyano-C-alkyloxy, C-alkylsulphonyloxy, phenylsulphonyloxy, carboxy-C-alkyloxy, C-alkyloxy-carbonyl-C-alkyloxy, aminocarbonyl-C-alkyloxy, C-alkyl-aminocarbonyl-C-alkyloxy, di-(C-alkyl)aminocarbonyl-C-alkyloxy, pyrrolidin-1-yl-carbonyl-C-alkyloxy, piperidin-1-ylcarbonyl-C-alkyloxy, morpholin-4-ylcarbonyl-C-alkyloxy, methylsulphanylmethoxy, methylsulphinylmethoxy, methylsulphonylmethoxy, C-cycloalkyloxy or C-cycloalkyl-C-alkyloxy group,'}, {'sub': 1-3', '1-3', '1-3', '1-3', '1-2', '1-2, 'd. a carboxy, C-alkyloxycarbonyl, carboxy-C-alkyl, C-alkyloxy-carbonyl-C-alkyl, aminocarbonyl, C-alkylaminocarbonyl, di-(C-alkyl)aminocarbonyl, morpholin-4-ylcarbonyl or cyano group,'}, {'sub': 1-2', '1-2', '1-2', '1-2', '1-2', '1-2', '1-2', '1-2', '1-2', '1-3', '1-2', '1-2', '1-2', '1-2', '1-', '1-2', '1-2, 'e. a nitro, amino, C-alkylamino, di-(C-alkyl)amino, cyano-C-alkylamino, [N-(cyano-C-alkyl)-N—C- ...

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Номер записи: 21
27-06-2013 дата публикации

TLR AGONISTS

Номер: US20130165455A1
Автор: Carson Dennis A., Chan Michael, Cottam Howard B., Takabayashi Kenji, Wu Christina C.N.
Принадлежит: The Regents of the University of California

The present invention provides for TLR agonist conjugates (compounds) and compositions, as well as methods of using them. The compounds of the invention are broad-spectrum, long-lasting, and non-toxic combination of synthetic immunostimulatory agents, which are useful for activating the immune system of a mammal, preferably a human and can help direct the pharmacophore to the receptor within the endosomes of target cells and enhance the signal transduction induced by the pharmacophore. 143-. (canceled)45. The compound of claim 44 , wherein Xis sulfur atom.46. The compound of claim 44 , wherein Xis oxygen atom.47. The compound of claim 44 , wherein Xis —NR— claim 44 , wherein Ris hydrogen claim 44 , Calkyl or substituted Calkyl; wherein the alkyl substituents are Ccycloalkyl claim 44 , hydroxy claim 44 , Calkoxy claim 44 , amino claim 44 , cyano claim 44 , or aryl.48. The compound of claim 47 , wherein Xis —NH—.49. The compound of claim 44 , wherein Rand Rtaken together form a heterocyclic ring or a substituted heterocyclic ring.50. The compound of claim 49 , wherein Rand Rtaken together form a substituted or unsubstituted morpholino claim 49 , piperidino claim 49 , pyrrolidino claim 49 , or piperazino ring.51. The compound of claim 44 , wherein Ris hydrogen claim 44 , Calkyl claim 44 , or substituted Calkyl.52. The compound of claim 51 , wherein Ris hydrogen claim 51 , CH— claim 51 , CH—CH— claim 51 , CHCHCH— claim 51 , hydroxyCalkylene claim 51 , or CalkoxyCalkylene.53. The compound of claim 52 , wherein Ris hydrogen claim 52 , CH— claim 52 , CH—CH— claim 52 , CH—O—CHCH— or CH—CH—O—CHCH—.54. The compound of claim 44 , wherein Ris hydrogen claim 44 , halogen claim 44 , or Calkyl.55. The compound of claim 54 , wherein Ris hydrogen claim 54 , chloro claim 54 , bromo claim 54 , CH— claim 54 , or CH—CH—.56. The compound of claim 44 , wherein the substituents on the alkyl claim 44 , aryl or heterocyclic groups are hydroxy claim 44 , Calkyl claim 44 , hydroxyCalkylene ...

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Номер записи: 22
04-07-2013 дата публикации

Substituted 2-(9h-purin-9-yl) acetic acid analogues as inhibitors of stat3

Номер: US20130172340A1
Автор: James Turkson, Patrick Gunning
Принадлежит: University of Central Florida Research Foundation Inc UCFRF

In one aspect, the invention relates to substituted purine analogs, derivatives thereof, and related compounds, which are useful as inhibitors of STAT protein activity; synthetic methods for making the compounds; pharmaceutical compositions comprising the compounds; and methods of treating disorders of uncontrolled cellular proliferation associated with a STAT protein activity dysfunction using the compounds and compositions. 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.

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Номер записи: 23
11-07-2013 дата публикации

PROCESS FOR THE PREPARATION OF CHIRAL 8-(3-AMINOPIPERIDIN-1-YL)-XANTHINES

Номер: US20130178485A1
Автор: DURAN Adil, NICOLA Thomas, Pachur Thorsten, Pfrengle Waldemar
Принадлежит: BOEHRINGER INGELHEIM INTERNATIONAL GMBH

The invention relates to an improved process for preparing enantiomerically pure 8-(3-aminopiperidin-1-yl)-xanthines. 2. The compound of formula (II) according to claim 1 , wherein{'sup': '1', 'sub': 'a', 'claim-text': {'sub': 'a', 'Ris a hydrogen, fluorine or chlorine atom or a cyano, methyl, ethyl, methoxy or ethoxy group,'}, 'Ris a phenylcarbonylmethyl, benzyl, naphthylmethyl, pyridinylmethyl, pyrimidinylmethyl, quinolinylmethyl, isoquinolinylmethyl, quinazolinylmethyl, quinoxalinylmethyl or naphthyridinylmethyl group wherein the aromatic or heteroaromatic moiety is in each case mono- or disubstituted by R, where the substituents may be the same or different, and'}{'sup': '2', 'Ris a methyl, ethyl, propyl, isopropyl, cyclopropyl or phenyl group, and'}{'sup': '3', 'Ris a 2-buten-1-yl, 3-methyl-2-buten-1-yl, 2-butyn-1-yl, 2-fluorobenzyl, 2-chlorobenzyl, 2-bromobenzyl, 2-iodobenzyl, 2-methylbenzyl, 2-(trifluoromethyl)benzyl or 2-cyanobenzyl group.'}3. The compound of formula (II) according to claim 2 , wherein{'sup': '1', 'Ris a cyanobenzyl, (cyanopyridinyl)methyl, quinolinylmethyl, (methylquinolinyl)methyl, isoquinolinylmethyl, (methylisoquinolinyl)methyl, quinazolinylmethyl, (methylquinazolinyl)methyl, quinoxazinylmethyl, (methylquinoxalinyl)methyl, (dimethylquinoxalinyl)methyl or naphthyridinylmethyl group,'}{'sup': '2', 'Ris a methyl, cyclopropyl or phenyl group, and'}{'sup': '3', 'Ris a 2-buten-1-yl, 3-methyl-2-buten-1-yl, 2-butyn-1-yl, 2-chlorobenzyl, 2-bromobenzyl or 2-cyanobenzyl group.'}4. The compound of formula (II) according to claim 3 , wherein{'sup': '1', 'Ris a (4-methylquinazolin-2-yl)methyl, (3-methylisoquinolin-1-yl)methyl or (3-cyanopyridin-2-yl)methyl group,'}{'sup': '2', 'Ris a methyl group, and'}{'sup': '3', 'Ris a 2-butyn-1-yl group.'}9. The method according to claim 8 , wherein the phthalyl protecting group is detached in the presence of ethanolamine.10. The method according to claim 8 , wherein the phthalyl protecting group is detached in ...

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Номер записи: 24
18-07-2013 дата публикации

Substituted quinazolines, the preparation thereof and the use thereof in pharmaceutical compositions

Номер: US20130184204A1
Автор: Frank Markus, Klein Thomas, Pfrengle Waldemar
Принадлежит: BOEHRINGER INGELHEIM INTERNATIONAL GMBH

The present invention relates to substituted quinazolines of formula (I): 2. The compound of formula (I) according to claim 1 , in whichR1 and R2 are the same or different and are independently selected from 3-(R)-amino-piperidin-1-yl, (2-amino-2-methyl-propyl)-methylamino and (2-(S)-amino-propyl)-methylamino;or a tautomer, enantiomer, diastereomer, mixture or salt thereof.3. The compound of formula (I) according to claim 1 , in which X and Y are the same claim 1 , or a tautomer claim 1 , enantiomer claim 1 , diastereomer claim 1 , mixture or salt thereof.6. Physiologically acceptable salt of the compound according to with an inorganic or organic acid or base.7. Pharmaceutical composition containing a compound of formula (I) according to claim 1 , or a physiologically acceptable salt thereof with an inorganic or organic acid or base claim 1 , optionally together with one or more pharmaceutically acceptable excipients.8. Use of a compound according to for preparing a pharmaceutical composition which is suitable for treating type II diabetes mellitus or obesity.9. Process for preparing a pharmaceutical composition according to claim 7 , characterised in that the compound of formula (I) or a physiologically acceptable salt thereof with an inorganic or organic acid or base is incorporated in one or more pharmaceutically acceptable excipients.10. A method of treating or preventing type II diabetes mellitus or obesity claim 1 , the method comprising administering the compound according to claim 1 , and optionally one or more other active substances claim 1 , to a patient.11. The method according to claim 10 , wherein the one or more other active substances is selected from metformin claim 10 , metformin; sulphonylureas claim 10 , nateglinide claim 10 , repaglinide claim 10 , thiazolidinediones (e.g. pioglitazone) claim 10 , PPAR-gamma agonists claim 10 , alpha-glucosidase blockers claim 10 , insulin or insulin analogues claim 10 , and GLP-1 and GLP-1 analogues.12. ...

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Номер записи: 25
18-07-2013 дата публикации

HETERO RING-FUSED IMIDAZOLE DERIVATIVE HAVING AMPK ACTIVATING EFFECT

Номер: US20130184240A1
Автор: Fujioka Masahiko, Ino Akira, Iwatsu Masafumi, Katou Manabu, Kojima Eiichi, Tanaka Nobuyuki, Tonogaki Keisuke
Принадлежит: Shionogi & Co., Ltd.

Disclosed is a compound which is useful as an AMPK activator. A compound represented by the formula: 3. The compound according to claim 2 , a pharmaceutically acceptable salt or solvate thereof claim 2 , wherein q is 1.4. The compound according to claim 3 , a pharmaceutically acceptable salt or solvate thereof claim 3 , wherein Rand Rare each independently substituted or unsubstituted alkyl.5. The compound according to claim 2 , a pharmaceutically acceptable salt or solvate thereof claim 2 , wherein Z is —NR—C(═O)—R.7. The compound according to claim 1 , a pharmaceutically acceptable salt or solvate thereof claim 1 ,wherein m is an integer of 1 to 3 or n is 1 or 2; and{'sup': '1', 'at least one of Ris substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted cycloalkenyl, or substituted or unsubstituted heterocyclyl.'}8. The compound according to claim 1 , a pharmaceutically acceptable salt or solvate thereof claim 1 ,wherein m is an integer of 1 to 3 or n is 1 or 2; and{'sup': '1', 'at least one of Ris substituted or unsubstituted aryl.'}10. The compound according to claim 9 , a pharmaceutically acceptable salt or solvate thereof claim 9 , wherein Ris substituted or unsubstituted aryl.14. The pharmaceutical composition according to claim 11 , wherein X is a single bond claim 11 , —S— claim 11 , —O— or —NR—.15. The pharmaceutical composition according to claim 14 , wherein X is —S— or —O—.16. The pharmaceutical composition according to claim 15 , wherein X is —O—.17. The pharmaceutical composition according to claim 11 , wherein Y is substituted or unsubstituted aryl claim 11 , or substituted or unsubstituted heteroaryl.18. The pharmaceutical composition according to claim 17 , wherein Y is substituted or unsubstituted aryl.20. The pharmaceutical composition according to claim 11 , wherein Y is substituted or unsubstituted alkyl.22. The pharmaceutical composition according to ...

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Номер записи: 26
01-08-2013 дата публикации

COMPOSITIONS AND METHODS FOR INDUCING CELL DEDIFFERENTIATION

Номер: US20130196989A1
Автор: Chen Shuibing, Ding Sheng, Schultz Peter G.
Принадлежит: The Scripps Research Institute

The present invention provides compounds, compositions and methods for dedifferentiating lineage committed mammalian cells into stem cells. The present invention also provides methods of inducing dedifferentiation of lineage committed mammalian cells into stem cells, which can be further differentiated into various lineage committed cells. Methods of identifying additional compounds useful for inducing dedifferentiation of lineage committed cells into stem cells are also provided. 19.-. (canceled)11. The compound of claim 10 , wherein Ris hydrogen claim 10 , and Ris Ccycloalkyl.12. The compound of claim 11 , wherein Ris cyclohexyl.16. A pharmaceutical composition comprising a compound of and a pharmaceutically acceptable carrier.17. The pharmaceutical composition of claim 16 , wherein Ris hydrogen claim 16 , and Ris Ccycloalkyl.18. The pharmaceutical composition of claim 17 , wherein Ris cyclohexyl.22. A method of inducing dedifferentiation of a lineage committed cell ex vivo claim 17 , the method comprising:{'claim-ref': {'@idref': 'CLM-00010', 'claim 10'}, 'contacting a lineage committed mammalian cell with a compound of , whereby the mammalian cell dedifferentiates into a multipotent stem cell.'}23. The method of claim 22 , further comprising detecting dedifferentiation of the mammalian cell into a multipotent stem cell.24. The method of claim 22 , whereby differentiation of the lineage committed mammalian cell into a multipotent stem cell is detected by detecting loss of expression of a marker gene expressed by the lineage committed mammalian cell.25. The method of claim 24 , wherein said lineage committed cell is a myoblast cell.26. The method of claim 25 , wherein the marker gene is a member selected from the group consisting of: MyoD claim 25 , Myf5 claim 25 , myosin claim 25 , CD56 and desmin.27. The method of claim 25 , wherein the myoblast cell is isolated from a mouse.28. The method of claim 25 , wherein the myoblast cell is isolated from a primate.29. ...

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Номер записи: 27
08-08-2013 дата публикации

USE OF DPAS AND CO-POLYMERS FOR HYPERLIPIDEMIA AND ATHEROSCLEROSIS ALONG WITH REDUCING FEEDING RATE AND ADIPOSE TISSUE WEIGHT OF OBESITY ANIMAL

Номер: US20130202549A1
Автор: Chen Ing-Jun
Принадлежит:

The disubstituted piperazine analogs (DPAs) derivative compound and DPAs amine complex compound disclosed in the present aspects have characterized by presented pharmaceutics having functions to improve lipolysis, such as inhibiting obesity hyperlipidemia, and atherosclerosis. 1. A method for inhibiting an obesity , comprising a step of:administering to a subject in need an effective amount of a pharmaceutical composition comprising one of a DPAs derivative compound and a DPAs amine complex compound.3. The method as claimed in claim 1 , wherein the DPAs derivative compound comprising one selected from a group consisting of a DPA-1 claim 1 , a DPA-2 claim 1 , a DPA-3 and a DPA-4.4. The method as claimed in claim 3 , wherein the DPA-1 includes a 7-[2-[4-(4-(2-chlorophenyl)piperazinyl]-ethyl]-1 claim 3 ,3-dimethyl xanthine.5. The method as claimed in claim 3 , wherein the DPA-2 includes a 7-[2-[4-(4-(2-methoxybenzene)piperazinyl]-ethyl]-1 claim 3 ,3-dimethylxanthine6. The method as claimed in claim 3 , wherein the DPA-3 includes a 7-[2-[4-(4-nitrobenzene)piperazinyl]-ethyl]-1 claim 3 ,3-dimethylxanthine.7. The method as claimed in claim 3 , wherein the DPA-4 includes a 7-[2-[4-(2-nitrobenzene)piperazinyl]-ethyl]-1 claim 3 ,3-dimethylxanthine.9. The method as claimed in claim 8 , wherein the halogen atom is one selected from a group consisting of a fluorine claim 8 , a chlorine claim 8 , a bromine and an iodine.10. The method as claimed in claim 8 , wherein the poly-γ-polyglutamic acid (γ-PGA) derivative is one selected from a group consisting of an alginate sodium claim 8 , a poly-γ-polyglutamic acid (γ-PGA) claim 8 , a poly-γ-polyglutamic acid sodium (γ-PGA sodium) claim 8 , a glutamic acid-L-lysine-L-tyrosine and a combination thereof.11. The method as claimed in claim 8 , wherein the co-polymer is one selected from a group consisting of a hyaluronic acid claim 8 , a polyacrylic acid claim 8 , a dextran sulfate claim 8 , a polymethacrylates (PMMA) claim 8 , an ...

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Номер записи: 28
08-08-2013 дата публикации

Arylamino Purine Derivatives, Preparation Method and Pharmaceutical Use Thereof

Номер: US20130203986A1
Автор: Wei Yuquan, YANG Shengyong
Принадлежит:

Arylamino purine derivatives represented by formula I and their preparation method are disclosed, wherein each substituent is defined as in the description. The derivatives have an inhibitory effect on non-small cell lung cancer with deletion mutation of exon 19 or L858R point mutation of exon 21 in epidermal growth factor receptor (EGFR). 2153-. (canceled) The present invention relates to the organically synthesized pharmaceutical field and in particular to arylamino purine derivatives, preparation method and pharmaceutical use thereof.Malignant tumor is one of the most severe diseases threatening the human physical health, and has become the second leading cause of death, right behind the cardiovascular disease.Moreover, the most recent statistical data indicate that the incidence rate and the death rate of malignant tumor are rising up year by year all over the world, especially in the developing countries.The chemotherapy is the most important treatment means for malignant tumor besides operation and radiotherapy. The traditional chemotherapeutics mainly act on DNA, RNA, microtubule protein and the like, which are the common parts involving the life and death of all cells, and therefore have low selectivity and high toxicity. The targeted medicines act on the key molecules in the tumor cell, which regulate the cell growth and proliferation and are quite different from the normal cell, and their signal transduction pathways. They have the advantages such as a high selectivity on the tumor cells and low toxicity to normal tissues, and therefore become a hot point in the study of anti-tumor drug.In many of molecules regulating signal transduction pathway of the cell, the family of protein kinases is the most important signal transduction molecule. It is found in the study that the occurrence and development of many tumors are relevant to the gene abnormality or excess activation of protein kinase. Therefore, protein kinases have become the most important anti-tumor ...

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Номер записи: 29
15-08-2013 дата публикации

Use of 6- substituted 9 - halogenalkyl purines for regulation of growth and development of whole plants, plant cells and plant organs; novel 6 - substituted 9 - halogenalkyl purines

Номер: US20130210632A1
Автор: Jiri Gruz, Karel Dolezal, Lucie Szucova, Lukas Spichal, Miroslav Strnad, Petr Galuszka, Vaclav Mik
Принадлежит: Palackeho Univerzita v Olomouci

The invention relates to 6-substituted 9-halogenalkyl purine derivatives of the general formula I wherein R6 is selected from the group comprising —NH-furfuryl, —NH-(4-hydroxy-3-methylbut-2-en-1-yl), —NH-(3-methylbut-2-en-1-yl), —NH-(4-hydroxy-3-methylbutyl), —NH-(4-hydroxy-1,3-dimethylbut-2-en-1-yl), —NH-(4-hydroxy-1,3-dimethylbutyl), —NH-benzyl, —NH-phenyl, wherein benzyl, furfuryl and phenyl can be unsubstituted or optionally substituted with 1 to 3 substituents selected from the group comprising hydroxy, halogen, methyl and methoxy, and R9 is selected from the group comprising C 1 -C 3 alkyl or C 1 -C 3 alkenyl wherein each of the groups is substituted with one or more halogen atoms, for use in the regulation of growth and development of plant cells, organs and/or whole plants. The invention also relates to preparations containing these derivatives and to novel to 6-substituted 9-halogenalkyl purines.

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Номер записи: 30
22-08-2013 дата публикации

Pyrazolopyrimidinyl inhibitors of ubiquitin-activating enzyme

Номер: US20130217682A1
Автор: François SOUCY, Indu T. Bharathan, Jeffrey L. Gaulin, Jeffrey P. Ciavarri, Mario Girard, Paul E. Fleming, Roushan AFROZE, Steven P. Langston, Tzu-Tshin WONG, Yingchun Ye
Принадлежит: Millennium Pharmaceuticals Inc

Disclosed are chemical entities that inhibit ubiquitin-activating enzyme (UAE), each of which is a compound of Formula I: or a pharmaceutically acceptable salt thereof, wherein Y is and W, Z, X Y , R Y1 , R Y2 and R Y3 are defined herein; pharmaceutical compositions comprising the chemical entities; and methods of using the chemical entities. These chemical entities are useful for treating disorders, particularly cell proliferation disorders, including cancers.

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Номер записи: 31
22-08-2013 дата публикации

Entecavir synthesis method and intermediate compound thereof

Номер: US20130217879A1
Автор: Zhiguo Zheng
Принадлежит: AUSUN PHARMATECH CO Ltd

The present invention relates to a preparation method for a medicine and an intermediate compound thereof, specifically, relates to a preparation method for entecavir, an intermediate compound thereof, and a synthesis method for the intermediate compound.

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Номер записи: 32
22-08-2013 дата публикации

PURINONE DERIVATIVE

Номер: US20130217880A1
Автор: YAMAMOTO Shingo, Yoshizawa Toshio
Принадлежит: ONO PHARMACEUTICAL CO., LTD.

Compounds represented by general formula (I) (all of the symbols in the formula conform to the definitions in the Description) are compounds that, in addition to having a Btk-selective inhibitory activity, exhibit an excellent metabolic stability and can avoid hepatotoxicity or the like, and as a consequence can provide safe therapeutic agents for diseases in which B cells or mast cells participate. 1. 6-amino-9-[(3R)-1-(2-butynoyl)-3-pyrrolidinyl]-7-(4-phenoxyphenyl)-7 ,9-dihydro-8H-purin-8-one , or a salt thereof.2. 6-amino-9-[(3R)-1-(2-butynoyl)-3-pyrrolidinyl]-7-(4-phenoxyphenyl)-7 ,9-dihydro-8H-purin-8-one. The present invention relates to compounds represented by general formula (I)(all of the symbols in the formula have the same definitions as given below), optical isomers thereof or their mixture, salts thereof, solvates thereof, N-oxides thereof, and prodrugs thereof (abbreviated below as “compounds of the present invention”).Bruton's tyrosine kinase (abbreviated below as “Btk”) belongs to the Tec family of kinases, which are non-receptor tyrosine kinases, and is selectively expressed in the B cell and myelocyte lines. Btk plays an important role in signal transduction in B cells and is a factor that contributes to the survival, differentiation, proliferation, and activation of B cells. Signaling in B cells via the B cell antigen receptor (BCR) induces a broad range of biological responses, and abnormal signal transduction here causes abnormal B cell activation and the formation of pathogenic autoantibodies. Btk is believed to form a link in the BCR-mediated signal transduction pathways into B cells. Thus, X-linked agammaglobulinemia (XLA) is known to be caused by a defect in the human Btk gene that results in the induction of abnormal B cell differentiation and a drastic decline in immunoglobulin production (refer to Non-patent Document 1). The symptoms of this disease include a substantial decline in B cells in the peripheral blood and an increased ...

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Номер записи: 33
29-08-2013 дата публикации

HETEROBICYCLIC COMPOUNDS

Номер: US20130225552A1
Автор: Allen Jennifer R., AMEGADZIE Albert, ANDREWS Kristin L., Brown James, Chen Jian J., Chen Ning, Harrington Essa Hu, Liu Qingyian, Nguyen Thomas T., Pickrell Alexander J., Qian Wenyuan, Rumfelt Shannon, Rzasa Robert M., Yuan Chester Chenguang, ZHONG Wenge
Принадлежит: Amgen Inc.

Heterobicyclic compounds of Formula (I): 6. The compound as in wherein the group —W-T-D< is selected from the group consisting of —N═CR—N<; NR—N═C<; —NR—(C═O)—N<; NR—CRR—(C═O)—N<; and —NR—(SO)—N<.7. The compound as in wherein the group —W-T-D< is selected from the group consisting of —CR═CR—N<; —CR═N—N<; —CRR—(C═O)—N<; —CRR—NR—(C═O)—N<; —CRR—O—(C═O)—N<; and —CRR—(SO)—N<.8. The compound as in wherein the group —W-T-D< is selected from the group consisting of —O—(C═O)—N<; and —O—CRR—(C═O)—N<.9. The compound as in wherein the group —W-T-D< is —CR═CR—N<.10. The compound as in wherein the group —W-T-D< is —N═CR—N<.11. The compound as in wherein J is CR; and each Ris independently H claim 1 , Calk claim 1 , —O—Calk claim 1 , or a saturated 3- claim 1 , 4- claim 1 , 5- or 6-membered monocyclic ring claim 1 , wherein each said ring contains 0 claim 1 , 1 claim 1 , 2 claim 1 , 3 claim 1 , or 4 N atoms and 0 claim 1 , 1 claim 1 , or 2 O or S atoms; wherein said monocyclic ring is independently substituted by 0 claim 1 , 1 claim 1 , 2 or 3 Rgroups.12. The compound as in wherein J is N; and each Ris independently H claim 1 , Calk claim 1 , —O—Calk claim 1 , or a saturated 3- claim 1 , 4- claim 1 , 5- or 6-membered monocyclic ring claim 1 , wherein each said ring contains 0 claim 1 , 1 claim 1 , 2 claim 1 , 3 claim 1 , or 4 N atoms and 0 claim 1 , 1 claim 1 , or 2 O or S atoms; wherein said monocyclic ring is independently substituted by 0 claim 1 , 1 claim 1 , 2 or 3 Rgroups.13. The compound as in wherein the group —W-T-D< is —CRR—(C═O)—N<.14. The compound as in wherein each Rand Ris independently H claim 13 , halo claim 13 , OH claim 13 , —O—Calk claim 13 , Calk or a saturated 3- claim 13 , 4- claim 13 , 5- or 6-membered monocyclic ring; or unsaturated 5- or 6-membered monocyclic ring; wherein each said ring contains 0 claim 13 , 1 claim 13 , or 2 N atoms and 0 claim 13 , 1 claim 13 , or 2 O or S atoms; wherein said RCalk or monocyclic ring is independently substituted by 0 ...

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Номер записи: 34
29-08-2013 дата публикации

HALOARYL SUBSTITUTED AMINOPURINES, COMPOSITIONS THEREOF,AND METHODS OF TREATMENT THEREWITH

Номер: US20130225564A1
Автор: CLAREEN STEVEN, PALANKI MOORTHY, PLANTEVIN-KRENITSKY VERONIQUE, SATOH YOSHITAKA
Принадлежит: SIGNAL PHARMACEUTICALS, LLC

Provided herein are Aminopurine Compounds having the following structure: 2. A compound of wherein Ris substituted or unsubstituted aryl.3. A compound of wherein Ris substituted or unsubstituted Cheterocycle.4. A compound of wherein Ris substituted or unsubstituted aryl.5. A compound of wherein Ris unsubstituted Ccycloalkyl.6. A compound of wherein Ris cyclohexyl substituted with one or more hydroxyl or aminocarbonyl claim 1 , cyano claim 1 , acylamino claim 1 , alkanesulfonylamino claim 1 , tetrazolyl claim 1 , triazolyl or imidazolyl groups.7. A compound of wherein Ris unsubstituted cyclopentyl.8. A compound of wherein Ris fluoro substituted aryl.13. A pharmaceutical composition comprising a compound of and a pharmaceutically acceptable carrier claim 1 , excipient or diluent.14. The pharmaceutical composition of suitable for oral claim 13 , parenteral claim 13 , mucosal claim 13 , transdermal or topical administration.15. A pharmaceutical composition comprising a compound of and a pharmaceutically acceptable carrier claim 9 , excipient or diluent.16. The pharmaceutical composition of suitable for oral claim 15 , parenteral claim 15 , mucosal claim 15 , transdermal or topical administration.17. A pharmaceutical composition comprising a compound of and a pharmaceutically acceptable carrier claim 10 , excipient or diluent.18. A pharmaceutical composition comprising a compound of and a pharmaceutically acceptable carrier claim 10 , excipient or diluent.19. A pharmaceutical composition comprising a compound of and a pharmaceutically acceptable carrier claim 11 , excipient or diluent.20. A pharmaceutical composition comprising a compound of and a pharmaceutically acceptable carrier claim 12 , excipient or diluent. This application is a continuation of U.S. application Ser. No. 12/779,083, filed May 13, 2010, currently allowed, which is a continuation of U.S. application Ser. No. 11/708,150, filed Feb. 15, 2007, now U.S. Pat. No. 7,759,342, issued Jul. 20, 2010, which is ...

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Номер записи: 35
05-09-2013 дата публикации

Sequence specific double-stranded dna/rna binding compounds and uses thereof

Номер: US20130231480A1
Автор: Anwar Rayan, Mizied Falah
Принадлежит: GENEARREST LTD

The present invention provides specific double-stranded DNA/RNA binding compounds having a polymeric structure, which are in fact, triplex forming molecules capable of binding tightly and specifically to predetermined sequences in the major groove of double stranded nucleic acid molecules; as well as pharmaceutical compositions comprising thereof. The triplex forming molecules and the pharmaceutical compositions of the invention can be used for various therapeutic applications such as site-specific modulation of gene expression, targeting of DNA or RNA damage, and gene knockout, as well as for diagnostic applications in vitro.

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Номер записи: 36
19-09-2013 дата публикации

NOVEL 2-ALKYNYL-N9-PROPARGYLADENINE AND MEDICINAL USE THEREOF

Номер: US20130245046A1
Автор: Deguchi Kazuki, Endo Kazuki, Yamada Kohei
Принадлежит: Yamasa Corporation

In the present invention, a novel 2-alkynyl-N9-propargyladenine represented by formula (I) 2. The compound or a pharmaceutically acceptable salt thereof according to claim 1 , wherein Ris bromo or chloro.3. The compound or a pharmaceutically acceptable salt thereof according to claim 1 , wherein Ris a 2-furyl group or a 2-triazolyl group.4. The compound or a pharmaceutically acceptable salt thereof according to claim 1 , wherein:{'sub': '2', 'Ris hydrogen; and'}{'sub': '3', 'Ris an alkyl group having 1 to 8 carbon atoms.'}5. The compound or a pharmaceutically acceptable salt thereof according to claim 1 , wherein Rand Rare a cycloalkyl group in which Rand Rare linked together.6. The compound or a pharmaceutically acceptable salt thereof according to claim 1 , which is 8-bromo-2-alkynyl-N-propargyladenine or 8-chloro-2-alkynyl-N-propargyladenine.7. The compound or a pharmaceutically acceptable salt thereof according to claim 1 , which is 8-(2-furyl)-2-alkynyl-N-propargyladenine or 8-(1 claim 1 ,2 claim 1 ,3-triazol-2-yl)-2-(1-alkynyl)-N-propargyladenine.8. The compound or a pharmaceutically acceptable salt thereof according to claim 1 , which is 8-bromo-2-(1-hydroxycycloalkyl)ethynyl-N-propargyladenine claim 1 , or 8-chloro-2-(1-hydroxycycloalkyl)ethynyl-N-propargyladenine.9. The compound or a pharmaceutically acceptable salt thereof according to claim 1 , which is 8-(2-furyl)-2-(1-hydroxycycloalkyl)ethynyl-N-propargyladenine or 8-(1 claim 1 ,2 claim 1 ,3-triazol-2-yl)-2-(1-hydroxy cycloalkyl)ethynyl-N-propargyladenine.10. A pharmaceutical composition comprising the compound or a pharmaceutically acceptable salt thereof according to claim 1 , and a pharmaceutically acceptable carrier.11. The pharmaceutical composition according to claim 10 , which is suitable as an adenosine Areceptor antagonist.12. The pharmaceutical composition according to claim 10 , which is suitable in the treatment of Parkinson's syndrome.13. The pharmaceutical composition according to claim 10 ...

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Номер записи: 37
26-09-2013 дата публикации

POLYMORPHIC FORMS OF (S)-2-(1-(9H-PURIN-6-YLAMINO)PROPYL)-5-FLUORO-3-PHENYLQUINAZOLIN-4(3H)-ONE

Номер: US20130252976A1
Автор: CARRA Ernest, Gerber Michael, Shi Bing, Sujino Keiko, TRAN Duong, Wang Fang
Принадлежит: Gilead Calistoga LLC

Polymorphs of (S)-2-(1-(9H-purin-6-ylamino)propyl)-5-fluoro-3-phenylquinazolin-4(3H)-one, compositions thereof, methods for their preparation, and methods for their use are disclosed. 1. A polymorph of (S)-2-(1-(9H-purin-6-ylamino)propyl)-5-fluoro-3-phenylquinazolin-4(3H)-one , wherein the polymorph is Form I having an X-ray powder diffraction pattern comprising characteristic peaks at about 17.7 degrees 2θ and about 24.9 degrees 2θ.2. The polymorph of claim 1 , wherein the X-ray powder diffraction pattern further comprises characteristic peaks at about 14.3 degrees 2θ claim 1 , about 17.2 degrees 2θ claim 1 , about 20.9 degrees 2θ claim 1 , and about 23.9 degrees 2θ.3. The polymorph of claim 1 , wherein the polymorph has an X-ray powder diffraction pattern substantially as shown in .4. A polymorph of obtained by:a) combining (S)-2-(1-(9H-purin-6-ylamino)propyl)-5-fluoro-3-phenylquinazolin-4(3H)-one with a solvent to form a mixture;b) heating the mixture to form a solution; and{'claim-ref': {'@idref': 'CLM-00001', 'claim 1'}, 'c) cooling the heated solution to form the polymorph of .'}5. The polymorph of claim 4 , wherein:the mixture is heated to a temperature of at least 50° C.; andthe heated solution is cooled to a temperature of at least about 30° C.6. A polymorph of (S)-2-(1-(9H-purin-6-ylamino)propyl)-5-fluoro-3-phenylquinazolin-4(3H)-one which is bioequivalent to the polymorph of .7. A polymorph of (S)-2-(1-(9H-purin-6-ylamino)propyl)-5-fluoro-3-phenylquinazolin-4(3H)-one claim 1 , wherein the polymorph is Form II having an X-ray powder diffraction pattern comprises a characteristic peak at about 18.6 degrees 2θ.8. The polymorph of claim 7 , wherein the X-ray powder diffraction pattern further comprises characteristic peaks at about 24.3 degrees 2θ and about 14.0 degrees 2θ.9. The polymorph of claim 7 , wherein the polymorph has an X-ray powder diffraction pattern substantially as shown in .10. A polymorph of obtained by:a) grinding the polymorphic Form I of ( ...

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Номер записи: 38
17-10-2013 дата публикации

Inhibiting Transient Receptor Potential Ion Channel TRPA1

Номер: US20130274273A1
Автор: Gu Yu Gui, III Chester A., Kimball Spencer D., Li Qingy, Lippa Blaise S., Metcalf, Ryan Dominic, Wu Xinyuan, Zou Dong
Принадлежит: Cubist Pharmaceuticals, Inc.

This disclosure describes a novel compounds and pharmaceutical compositions for inhibiting the TRPA1 ion channel and/or medical conditions related to TRPA1, such as pain. 1. A method for treating or ameliorating pain, comprising intravenously administering to an animal or human an effective amount of a pharmaceutical composition comprising a compound of Formula (Ia), or a pharmaceutically acceptable salt thereof: This patent application is a continuation of U.S. patent application Ser. No. 13/571,288, filed Aug. 9, 2012, which claims priority to U.S. provisional patent application Ser. No. 61/521,705, filed Aug. 9, 2011. The contents of these applications are incorporated herein by reference in their entireties.The present disclosure relates to compounds and methods for treating pain, for example by inhibiting the Transient Receptor Potential A1 ion channel (TRPA1).TRPA1 is a non-selective cation channel related to pain sensation in humans. TRPA1 is found in sensory neurons and functions as a signal transduction receptor linking inflammation to pain. Activation of TRPA1 can cause pain by inducing firing of nociceptive neurons and driving central sensitization in the spinal cord. TRPA1 stimulation can also increase firing of sensory neurons, leading to the release of pro-inflammatory neuropeptides such as NK-A, substance P and CGRP (which induce vasodilation and help recruit immune cells). A variety of endogenous reactive compounds produced during inflammation activate TRPA1 (including 4-hydroxynonenal released during liposome peroxidation; cyclopentane prostaglandins synthesized by COX enzymes; hydrogen peroxide produced by oxidative stress). TRPA1 can also be activated by a variety of stimuli, including natural products (e.g., allyl isothiocyanate, or AITC), environmental irritants (e.g., acrolein), amphipathic molecules (e.g., trinitrophenol and chlorpromazine) and pharmacological agents. Activation of TRPA1 also sensitizes TRPA1 to cold. Furthermore, a gain-of- ...

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Номер записи: 39
24-10-2013 дата публикации

CYCLOPROPANECARBOXYLATE ESTERS OF PURINE ANALOGUES

Номер: US20130281517A1
Автор: Chang Pei-Teh, Chern Ji-Wang, LAI Shin-yu
Принадлежит:

Cyclopropanecarboxylate esters of purine analogues, method of making and using the same for treating herpes virus infections and tumors are disclosed. 2. The compound of claim 1 , wherein{'sub': x', 'y, 'Rand Rare each independently hydrogen or methyl; and'}{'sub': 'y', 'Ris hydrogen, methyl, trifluoromethyl, phenyl, 4-bromophenyl, 2-furyl, or 2-pyridyl.'}3. The compound of claim 2 , wherein{'sub': x', 'z, 'Rand Rare each independently hydrogen; and'}{'sub': 'y', 'Ris hydrogen, methyl, trifluoromethyl, phenyl, 4-bromophenyl, 2-furyl, or 2-pyridyl.'}4. The compound of claim 2 , wherein{'sub': 'x', 'Ris methyl; and'}{'sub': y', 'z, 'Rand Rare each independently hydrogen.'}5. The compound of claim 2 , wherein{'sub': 'x', 'Ris hydrogen; and'}{'sub': y', 'z, 'Rand Rare each independently methyl.'}6. The compound of claim 2 , wherein the compound is selected from the group consisting of1-amino-cyclopropanecarboxylic acid 2-(2-amino-6-oxo-1,6-dihydro-purin-9-yl methoxy)-3-hydroxypropyl ester,1-amino-2-(4-bromo-phenyl)-cyclopropanecarboxylic acid 2-(2-amino-6-oxo-1,6-dihydro-purin-9-ylmethoxy)-3-hydroxypropyl ester,1-amino-2-phenyl-cyclopropanecarboxylic acid 2-(2-amino-6-oxo-1,6-dihydro-purin-9-ylmethoxy)-3-hydro propyl ester,1-amino-2-methyl-cyclopropanecarboxylic acid 2-(2-amino-6-oxo-1,6-dihydro-purin-9-ylmethoxy)-3-hydroxypropyl ester,1-amino-2-trifluoromethyl-cyclopropanecarboxylic acid 2-(2-amino-6-oxo-1,6-dihydro-purin-9-ylmethoxy)-3-hydroxypropyl ester,1-amino-2-furan-2-yl-cyclopropanecarboxylic acid 2-(2-amino-6-oxo-1,6-dihydro-purin-9-ylmethoxy)-3-hydroxypropyl ester, and1-amino-2-pyridin-2-yl-cyclopropanecarboxylic acid 2-(2-amino-6-oxo-1,6-dihydro-purin-9-yl-methoxy)-3-hydroxypropyl ester.7. The compound of claim 2 , wherein the compound is 1-methylamino-cyclopropanecarboxylic acid 2-(2-amino-6-oxo-1 claim 2 ,6-dihydro-purin-9-ylmethoxy)-3-hydroxypropyl ester.8. The compound of claim 2 , wherein the compound is 1-amino-2 claim 2 ,2-dimethyl- ...

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Номер записи: 40
31-10-2013 дата публикации

N-CONTAINING HETEROARYL DERIVATIVES AS JAK3 KINASE INHIBITORS

Номер: US20130289015A1
Автор: Escrich Sergio Rodriguez, Gonzalez Maria Cristina Sicre, Rosales Carmen Almansa, Solana Jorge Salas, Soliva Robert Soliva
Принадлежит:

N-containing heteroaryl derivatives of formula I or II, wherein the meanings for the various substituents are as disclosed in the description. These compounds are useful as JAK, particularly JAK3, kinase inhibitors. 151-. (canceled)53. The method according to claim 52 , wherein the disease is selected from the group consisting of transplant rejection claim 52 , immune claim 52 , autoimmune or inflammatory diseases claim 52 , neurodegenerative diseases claim 52 , and proliferative disorders.54. The method according to claim 52 , wherein the disease is selected from the group consisting of transplant rejection claim 52 , rheumatoid arthritis claim 52 , psoriatic arthritis claim 52 , psoriasis claim 52 , type I diabetes claim 52 , complications from diabetes claim 52 , multiple sclerosis claim 52 , systemic lupus erythematosus claim 52 , atopic dermatitis claim 52 , mast cell-mediated allergic reactions claim 52 , inflammatory or autoimmune ocular diseases claim 52 , leukemias claim 52 , lymphomas claim 52 , and thromboembolic and allergic complications associated with leukemias and lymphomas.55. (canceled) The present invention relates to a new series of N-containing heteroaryl derivative, as well as to processes for their preparation, to pharmaceutical compositions comprising them and to their use in therapy.The Janus kinases (JAKs) are cytoplasmic protein tyrosine kinases that play pivotal roles in pathways that modulate cellular functions in the lympho-hematopoietic system that are critical for cell proliferation and cell survival. JAKs are involved in the initiation of cytokine-triggered signaling events by activating through tyrosine phosphorylation the signal transducers and activators of transcription (STAT) proteins. JAK/STAT signaling has been implicated in the mediation of many abnormal immune responses such as transplant rejection and autoimmune diseases, as well as in solid and hematologic malignancies such as leukemias and lymphomas and in ...

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Номер записи: 41
31-10-2013 дата публикации

INHIBITORS OF E1 ACTIVTING ENZYMES

Номер: US20130289037A1
Автор: Langston Steven P., Olhava Edward J., Vyskocil Stepan
Принадлежит:

This invention relates to compounds that inhibit E1 activating enzymes, pharmaceutical compositions comprising the compounds, and methods of using the compounds. The compounds are useful for treating disorders, particularly cell proliferation disorders, including cancers, inflammatory and neurodegenerative disorders; and inflammation associated with infection and cachexia. 1. (canceled)3. The compound of claim 2 , or a pharmaceutically acceptable salt thereof claim 2 , wherein:{'sup': g', '1g', '2g', '1', '1g', '1', '2g', '1', '1', '1g', '1', '1', '2g, 'sub': 1-6', '1-6, 'claim-text': [{'sup': 1', '3a', '3b', '5', '5', '4', '4', '4', '4', '4', '4', '4', '4', '4', '4', '4', '4', '4', '4', '4', '4', '4', '4', '4', '4', '4', '6', '1, 'sub': 1-6', '2', '2', '2', '2', '2', '2, 'Tis a Calkylene chain substituted with 0-2 independently selected Ror R, wherein the alkylene chain optionally is interrupted by —C(R)═C(R)—, —C≡C—, —O—, —S—, —S(O)—, —S(O)—, —SON(R)—, —N(R)—, —N(R)C(O)—, —NRC(O)N(R)—, —N(R)C(═NR)—N(R)—, —N(R)—C(═NR)—, —N(R)CO—, —N(R)SO—, —N(R)SON(R)—, —OC(O)—, —OC(O)N(R)—, —C(O)—, —CO—, —C(O)N(R)—, —C(═NR)—N(R)—, —C(NR)═N(R)—, —C(═NR)—O—, or —C(R)═N—O—, and wherein Tor a portion thereof optionally forms part of a 3-7 membered ring;'}, {'sup': 1', '5', '5', '4', '4', '4', '4', '4', '4', '4', '4', '4', '4', '4', '4', '4', '4', '4', '4', '4', '4', '4', '4', '4', '4', '4', '4', '4', '4', '4', '4', '6, 'sub': 2', '2', '2', '2', '2', '2, 'Vis —C(R)═C(R)—, —C≡C—, —O—, —S—, —S(O)—, —S(O)—, —SON(R)—, —N(R)—, —N(R)C(O)—, —NRC(O)N(R)—, —N(R)C(═NR)—N(R)—, —N(R)C(═NR)—, —N(R)CO—, —N(R)SO—, —N(R)SON(R)—, —OC(O)—, —OC(O)N(R)—, —C(O)—, —CO—, —C(O)N(R)—, —C(O)N(R)—O—, —C(O)N(R)C(═NR)—N(R)—, —N(R)C(═NR)—N(R)—C(O)—, —C(═NR)—N(R)—, —C(NR)═N(R)—, —C(═NR)—O—, or —C(R)═N—O—;'}, {'sup': '1g', 'each Rindependently is an optionally substituted aryl, heteroaryl, heterocyclyl, or cycloaliphatic ring;'}, {'sup': 2g', '5', '5', '5', '5', '6', '6', '6', '4', '4', '4', '5', '4', '4', '4', '4', ...

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Номер записи: 42
14-11-2013 дата публикации

USE OF A DPP-4 INHIBITOR IN PODOCYTES RELATED DISORDERS AND/OR NEPHROTIC SYNDROME

Номер: US20130303462A1
Автор: Hocher Berthold, Klein Thomas, MARK Michael, SHARKOVSKA Yuliya, von EYNATTEN Maximilian
Принадлежит: BOEHRINGER INGELHEIM INTERNATIONAL GMBH

The present invention relates to methods for treating and/or preventing podocytes related disorders and/or nephrotic syndrome comprising the administration of an effective amount of a certain DPP-4 inhibitor, as well as to the use of a certain DPP-4 inhibitor for treating and/or preventing a metabolic disease in a patient with or at risk of podocytes related disorders and/or nephrotic syndrome. 2. The method according to claim 1 , wherein the DPP-4 inhibitor is linagliptin claim 1 , optionally in combination with one or more other active agents claim 1 , and the method is for treating claim 1 , preventing and/or reducing the risk of podocyte related disorders claim 1 , disturbance of podocyte function claim 1 , podocyte loss or injury claim 1 , and/or podocytopathy.3. The method according to claim 1 , wherein the DPP-4 inhibitor is linagliptin claim 1 , optionally in combination with one or more other active agents claim 1 , and the method is for treating claim 1 , preventing or reducing the risk of nephrotic syndrome.4. The method according to claim 3 , wherein the nephrotic syndrome includes claim 3 , is caused by or is associated with minimal change disease (MCD) claim 3 , membranous nephropathy (MN) and/or focal segmental glomerulosclerosis (FSGS).5. The method according to claim 4 , wherein the nephrotic syndrome is primary or secondary.6. The method according to claim 4 , wherein the nephrotic syndrome is resistant or refractory to conventional therapy.7. The method according to claim 1 , wherein the DPP-4 inhibitor is linagliptin claim 1 , optionally in combination with one or more other active agents claim 1 , and the method is for treating claim 1 , preventing and/or reducing the risk of minimal change disease (MCD) claim 1 , membranous nephropathy (MN) and/or focal segmental glomerulosclerosis (FSGS).8. The method according to claim 1 , wherein the DPP-4 inhibitor is linagliptin claim 1 , optionally in combination with one or more other active agents claim ...

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Номер записи: 43
14-11-2013 дата публикации

COMPOUNDS AND COMPOSITIONS FOR TREATING CHEMICAL WARFARE AGENT-INDUCED INJURIES

Номер: US20130303521A1
Автор: Chong Jayhong A.
Принадлежит: HYDRA BIOSCIENCES, INC

Compounds and compositions for treating injuries caused by exposure to chemical warfare agents are described herein. 122-. (canceled)24. The compound of claim 23 , wherein{'sup': '2', 'sub': 1', '6, 'a. Ris H or C-Calkyl;'}{'sup': '6', 'b. L is C(O)NR;'}{'sup': 3', '7, 'sub': 4', '14, 'c. Ris C-Ccyclyl, heterocyclyl, aryl, or heteroaryl, optionally substituted with R;'}{'sup': '6', 'd. each Ris H;'}{'sup': 7', '8, 'sub': 1', '6', '2', '6', '2', '6, 'e. Ris C-Calkyl, C-Calkenyl, C-Calkynyl, cyclyl, heterocyclyl, aryl, heteroaryl, halo, hydroxyl, alkoxy, thiol, alkylthio, aryloxy, arylalkoxy, amino, alkylamino, dialkylamino, thioyl, alkylthioyl, sulfonyl, sulfonamidyl, amido, urea, sulfonylurea, hydroxyl alkoxyl, alkoxy alkoxyl, acyl, nitro, or cyano, each of which is optionally substituted with 1-3 R;'}{'sup': '8', 'sub': 1', '6', '2', '6', '2', '6', '3, 'f. each Ris independently C-Calkyl, C-Calkenyl, or C-Calkynyl, halo, hydroxyl, alkoxy, thiol, alkylthio, aryloxy, amino, alkylamino, dialkylamino, thioyl, sulfonyl, sulfonamidyl, amido, urea, sulfonylurea acyl, nitro, cyano, cyclyl, heterocyclyl, aryl, or heteroaryl, wherein said heterocyclyl can be substituted at one or more positions with halogen, alkyl, aralkyl, alkenyl, alkynyl, cycloalkyl, hydroxyl, amino, nitro, sulfhydryl, imino, amido, phosphate, phosphonate, phosphinate, carbonyl, carboxyl, silyl, ether, alkylthio, sulfonyl, ketone, aldehyde, ester, a heterocyclyl, an aromatic or heteroaromatic moiety, —CF, and —CN;'}{'sup': '9', 'g. Ris H;'}{'sup': 11', '12', '8, 'sub': 1', '6', '2', '6', '2', '6, 'h. each of R-Ris, independently, H, C-Calkyl, C-Calkenyl, or C-Calkynyl, halo, hydroxyl, alkoxy, amino, alkylamino, thiol, alkylthiol, nitro, or cyano, each of which is optionally substituted with 1-2 R;'}i. m is 1 andj. n is 0.25. The compound of claim 24 , wherein{'sup': '2', 'sub': 1', '6, 'a. Ris C-Calkyl;'}{'sup': 3', '7, 'b. Ris aryl or heteroaryl, substituted with R;'}{'sup': 7', '8, 'c. Ris aryl or ...

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Номер записи: 44
14-11-2013 дата публикации

USE OF A DPP-4 INHIBITOR IN SIRS AND/OR SEPSIS

Номер: US20130303554A1
Автор: DAIBER Andreas, DUGI Klaus, Klein Thomas, MARK Michael, MUENZEL Thomas
Принадлежит: BOEHRINGER INGELHEIM INTERNATIONAL GMBH

The present invention relates to methods for treating and/or preventing SIRS and/or sepsis comprising the administration of an effective amount of a certain DPP-4 inhibitor, as well as to the use of a certain DPP-4 inhibitor for treating and/or preventing a metabolic disease in a patient with or at risk of SIRS and/or sepsis. 2. The method according to claim 1 , wherein the DPP-4 inhibitor is linagliptin claim 1 , optionally in combination with one or more other active agents claim 1 , and the method is for increasing survival rate and/or reducing mortality claim 1 , morbidity or hospitalisation of a patient with or at risk of SIRS and/or sepsis (SIRS/sepsis).3. The method according to wherein the DPP-4 inhibitor is claim 1 , optionally in combination with one or more other active agents claim 1 , and the method is for treating claim 1 , preventing or reducing the likelihood or risk of complications associated with SIRS and/or sepsis claim 1 , such as e.g. severe SIRS/sepsis claim 1 , SIRS/septic shock and/or multi-organ failure.4. The method according to claim 1 , wherein the DPP-4 inhibitor is linagliptin claim 1 , optionally in combination with one or more other active agents claim 1 , and the method is for reducing the risk or likelihood of multi-organ failure in a patient with or at risk of SIRS and/or sepsis (SIRS/sepsis).5. The method according to claim 1 , wherein the DPP-4 inhibitor is linagliptin claim 1 , optionally in combination with one or more other active agents claim 1 , and the method is for reducing the risk or likelihood of septic shock in a patient with or at risk of SIRS and/or sepsis (SIRS/sepsis).6. The method according to claim 1 , wherein the DPP-4 inhibitor is linagliptin claim 1 , optionally in combination with one or more other active agents claim 1 , and the method is for reducing the risk or likelihood of severe sepsis in a patient with or at risk of SIRS and/or sepsis (SIRS/sepsis).7. The method according to claim 1 , wherein the DPP- ...

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Номер записи: 45
14-11-2013 дата публикации

Inhibitors of Human EZH2 and Methods of Use Thereof

Номер: US20130303555A1
Автор: Christopher J. Sneeringer, Kevin W. Kuntz, Margaret D. Scott, Robert A. Copeland, Roy M. Pollock, Sarah K. Knutson, Victoria M. Richon
Принадлежит: Epizyme Inc

The invention relates to determining the presence of an EZH2 gene mutation in a sample from a subject and inhibition of wild-type and certain mutant forms of human histone methyltransferase EZH2, the catalytic subunit of the PRC2 complex which catalyzes the mono-through tri-methylation of lysine 27 on histone H3 (H3-K27). In one embodiment the inhibition is selective for the mutant form of the EZH2, such that trimethylation of H3-K27, which is associated with certain cancers, is inhibited. The methods can be used to treat cancers including follicular lymphoma and diffuse large B-cell lymphoma (DLBCL). Also provided are methods for identifying small molecule selective inhibitors of the mutant forms of EZH2 and also methods for determining responsiveness to an EZH2 inhibitor in a subject.

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Номер записи: 46
21-11-2013 дата публикации

Use of TRPA1 Antagonists to Prevent or Treat Infections Caused by Biological-Warfare Agents

Номер: US20130310345A1
Автор: Moran Magdalene M.
Принадлежит:

Provided are methods for preventing and treating injuries caused by exposure to biological warfare agents. The methods include administering to a subject in need thereof an effective amount of a TRPA1 antagonist or a pharmaceutically acceptable salt thereof. In an embodiment the TRPA1 antagonist is selected from the group consisting of compounds of formula I 1. A method of preventing or treating an injury resulting from exposure to a biological-warfare agent , comprising administering to a subject in need thereof an effective amount of a TRPA1 antagonist or a pharmaceutically acceptable salt thereof.4. The method of claim 2 , wherein the TRPA1 antagonist is administered orally.5. The method of claim 2 , wherein the TRPA1 antagonist is administered via intramuscular injection.6. The method of claim 2 , wherein the TRPA1 antagonist is administered topically.7. The method of claim 2 , wherein the TRPA1 antagonist is administered by topical ocular administration.8. The method of claim 2 , wherein the TRPA1 antagonist is administered prior to the exposure to the biological-warfare agent.9. The method of claim 2 , wherein the TRPA1 antagonist is administered after exposure to the biological-warfare agent.10Bacillus anthracisBurkholderia malleiBurkholderia pseudomalleiClostridium botulinumFrancisella tularensisVibrio choleraeYersinia pestis. The method of claim 2 , wherein the biological-warfare agent is (anthrax) claim 2 , (glanders) claim 2 , (melioidosis) claim 2 , toxin (botulism) claim 2 , Ebola virus claim 2 , (tularemia) claim 2 , Marburg virus claim 2 , (cholera) claim 2 , alphaviruses claim 2 , Venezuelan equine encephalitis virus claim 2 , eastern equine encephalitis virus claim 2 , western equine encephalitis virus claim 2 , filoviruses claim 2 , arenaviruses claim 2 , Lassa virus claim 2 , Machupo virus or (plague).11Bacillus anthracis. The method of claim 2 , wherein the biological-warfare agent is (anthrax).12Yersinia pestis. The method of claim 2 , wherein ...

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Номер записи: 47
21-11-2013 дата публикации

MULTI-MODALITY MOLECULAR IMAGING HIGH-THROUGHPUT ASSAY FOR IDENTIFYING HEAT SHOCK PROTEIN 90 (HSP90) INHIBITORS

Номер: US20130310347A1
Автор: Chan Carmel, Gambhir Sanjiv S., Hoehne Aileen, Paulmurugan Ramasamy, Solow-Cordero David E.
Принадлежит: THE BOARD OF TRUSTEES OF THE LELAND STANFORD JUNIOR UNIVERSITY

High throughput methods for identifying novel inhibitors of Hsp90 chaperone protein folding are disclosed. The inhibitors so identified disrupt the binding of p23 to either Hsp90α or Hsp90β and have selective activity against the proliferation of cancer cells. In particular are provided embodiments of therapeutic compositions that comprise at least one inhibitor of an Hsp90 chaperone activity, the inhibitor being any of the compounds designated as CP1-CP19 as shown in FIGS. A-D or a 2-(trifluoromethyl)pyrimidin-2-yl)thio)acetamide derivatives. 2. The therapeutic composition of claim 1 , wherein Ris a thiophene claim 1 , a furan claim 1 , or a substituted phenyl claim 1 , wherein the substituted phenyl is a methoxyphenyl claim 1 , an halogenated phenyl claim 1 , or a dimethoxyphenyl.3. The therapeutic composition of claim 1 , wherein the inhibitor has the formula I and is selected from compounds CP9 and A1-A62 of .5. The therapeutic composition of claim 4 , wherein Ris a thiophene claim 4 , a furan claim 4 , phenyl claim 4 , or a substituted phenyl claim 4 , wherein the substituted phenyl is a methoxyphenyl claim 4 , an halogenated phenyl claim 4 , or a dimethoxyphenyl.6. The therapeutic composition of claim 4 , wherein the inhibitor is selected from compounds CP9 and A1-A62 of .8. The therapeutic composition of claim 1 , wherein the inhibitor is CP9 claim 1 , A17 claim 1 , A29 claim 1 , or A61 claim 1 , or a combination thereof.9. The therapeutic composition of further comprising a pharmaceutically acceptable carrier.11. The method of claim 10 , wherein Ris a thiophene claim 10 , a furan claim 10 , phenyl claim 10 , or a substituted phenyl claim 10 , wherein the substituted phenyl is a methoxyphenyl claim 10 , an halogenated phenyl claim 10 , or a dimethoxyphenyl.12. The method of claim 10 , wherein the inhibitor has the formula I and is selected from compounds CP9 and A1-A62 of .14. The method of claim 13 , wherein Ris a thiophene claim 13 , a furan claim 13 , ...

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Номер записи: 48
21-11-2013 дата публикации

Fluoro-homoneplanocin A and nucleoside derivatives, method for the synthesis thereof, and the pharmaceutical compositions comprising the same as an active component for treatment of cancer

Номер: US20130310403A1
Автор: Lak Shin Jeong
Принадлежит: Industry Collaboration Foundation of Ewha University

The present invention relates to a fluoro-homoneplanocin A, its nucleoside derivative, and synthetic methods. The novel fluoro-homoneplanocin A and its nucleoside derivative in the present invention have an effect on cancer prevention or treatment, and therefore can be used as anticancer drugs.

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Номер записи: 49
21-11-2013 дата публикации

INHIBITORS OF P75 RECEPTOR AND THEIR USES

Номер: US20130310404A1
Автор: Nedev Hinyu, Saragovi Horacio Uri
Принадлежит:

Novel p75 receptor antagonist compounds and compositions and uses thereof for the prevention and treatment of p75-associated disorders, such as neurodegenerative diseases, are described. 8. A pharmaceutical composition comprising the compound of and a pharmaceutically acceptable carrier.10. A method for inhibiting p75 receptor in a subject comprising administering the compound of to the subject claim 1 , such that p75 receptor is inhibited in said subject.11. The method of claim 10 , wherein p75 receptor activation is inhibited in said subject.12. The method of claim 10 , wherein p75 receptor function is inhibited in said subject.13. A method for preventing or treating a disease or condition characterized by p75 activation in a subject claim 1 , comprising administering an effective amount of the compound of to the subject.14. The method of claim 13 , wherein p75 receptor activation is inhibited in said subject.15. The method of claim 13 , wherein p75 receptor function is inhibited in said subject.16. The method of claim 13 , wherein the disease or condition is a neurodegenerative disease.17. The method of claim 16 , wherein the neurodegenerative disease is selected from the group consisting of Alzheimer's disease claim 16 , Down's syndrome claim 16 , Creutzfeldt-Jacob disease claim 16 , kuru claim 16 , scrapie claim 16 , transmissible mink encephalopathy claim 16 , Riley-Day familial dysautonomia claim 16 , multiple system atrophy claim 16 , amyotrophic lateral sclerosis (ALS) claim 16 , glaucoma claim 16 , neuropathy claim 16 , ischemia claim 16 , hypoxia claim 16 , neural injury claim 16 , Huntington's disease claim 16 , epilepsy claim 16 , Parkinson's disease claim 16 , spinal cord injury and neuroblastoma.18. The method of claim 16 , wherein the neurodegenerative disease is a disease which can be treated with agents that activate a Trk receptor claim 16 , with neurotrophins claim 16 , and/or with neurotrophin-derived peptides or peptidomimetics.19. The method ...

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Номер записи: 50
28-11-2013 дата публикации

DIARYL ETHER LINKED PYRROLO [2,1-c][1,4] BENZODIAZEPINE HYBRIDS AND PROCESS FOR THE PREPARATION THEREOF

Номер: US20130317011A1
Автор: Ahmed Kamal, Arutla Viswanath, Earla Vijaya Bharathi, Farheen Sulthana, Gadupudi Ramakrishna, Jayanti Naga Srirama Chandra Murty
Принадлежит: Council of Scientific and Industrial Research CSIR

The present invention provides a compound of general formula A, useful as potential anticancer agents against eleven human cancer cell lines. The present invention further provides a process for the preparation of diaryl ether linked pyrrolo[2,1-c][1,4]benzodiazepine conjugates attached through different alkane spacers of general formula A.

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Номер записи: 51
28-11-2013 дата публикации

NOVEL PURINYLPYRIDINYLAMINO-2,4-DIFLUOROPHENYL SULFONAMIDE DERIVATIVE, PHARMACEUTICALLY ACCEPTABLE SALT THEREOF, PREPARATION METHOD THEREOF, AND PHARMACEUTICAL COMPOSITION WITH INHIBITORY ACTIVITY AGAINST RAF KINASE, CONTAINING SAME AS ACTIVE INGREDIENT

Номер: US20130317023A1
Автор: KIM Nam Doo, Kim Seung Yong, Shim Eun Kyong, Shim Tae Bo
Принадлежит: YOUAI CO., LTD.

A novel purinylpyridinylamino-2,4-difluorophenyl sulfonamide derivative, a pharmaceutically acceptable salt thereof, a preparation method thereof, and a pharmaceutical composition with an inhibitory activity against Raf kinase, containing the same as an active ingredient are provided. The purinylpyridinylamino-2,4-difluorophenyl sulfonamide derivative of the present invention effectively regulates the activity of B-Raf kinase, and thus may be useful for preventing or treating cancers induced by the over-activation of Raf kinase, especially various melanoma, colorectal cancer, prostate cancer, thyroid cancer, ovarian cancer and the like. 2. The novel purinylpyridinylamino-2 claim 1 ,4-difluorophenyl sulfonamide derivative or the pharmaceutically acceptable salt thereof according to claim 1 , wherein the R is methyl; ethyl; propyl; isopropyl; butyl; isobutyl; cyclopropyl; cyclobutyl; cyclopentyl; cyclohexyl; C-Caryl non-substitutable or substituted with one or more selected from the group consisting of chloro claim 1 , fluoro claim 1 , bromo claim 1 , methyl claim 1 , ethyl claim 1 , propyl claim 1 , isopropyl claim 1 , butyl claim 1 , isobutyl claim 1 , methoxy claim 1 , ethoxy claim 1 , propoxy claim 1 , butoxy claim 1 , trifluoromethoxy claim 1 , fluoromethoxy claim 1 , difluoromethoxy claim 1 , and trifluoroethoxy; C-Csingle or double ring heteroaryl non-substitutable or substituted with one or more selected from the group consisting of chloro claim 1 , fluoro claim 1 , bromo claim 1 , methyl claim 1 , ethyl claim 1 , propyl claim 1 , isopropyl claim 1 , butyl claim 1 , isobutyl claim 1 , methyloxycarbonyl claim 1 , ethyloxycarbonyl claim 1 , propyloxycarbonyl claim 1 , butyloxycarbonyl claim 1 , t-butyloxycarbonyl claim 1 , and dioxolanyl; C-Cheterocycloalkyl non-substitutable or substituted with one or more selected from the group consisting of chloro claim 1 , fluoro claim 1 , bromo claim 1 , methyl claim 1 , ethyl claim 1 , propyl claim 1 , isopropyl claim 1 , ...

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Номер записи: 52
05-12-2013 дата публикации

ATROPISOMERS OF P13K-INHIBITING COMPOUNDS

Номер: US20130324561A1
Автор: Evarts Jerry, Ulrich Roger G.
Принадлежит: GILEAD CALISTROGA LLC.

The invention provides compounds, compositions and methods to treat certain inflammatory conditions or cancers by administering a compound that inhibits PI3K isoforms, wherein the compounds are optically active atropisomers. It provides optically active stereoisomers of a class of pyrazole-containing compounds, which are useful for these methods, and provides methods to obtain these compounds as well as pharmaceutical compositions containing these compounds. 148-. (canceled)50. The compound according to claim 49 , wherein:W is selected from the group consisting of H, F, Cl, Me, and OMe;Y is H or F;X is selected from the group consisting of Cl, Me and OMe;V is H or Me; andU is alkynyl or aryl, each of which is optionally substituted,or a pharmaceutically acceptable salt thereof.53. A composition comprising a compound according to claim 49 , and a pharmaceutically acceptable carrier.56. A composition comprising a compound according to claim 54 , and a pharmaceutically acceptable carrier.57Pneumocystis carinii. A method of treating a condition in a mammal claim 54 , wherein the condition is selected from the group consisting of chronic inflammatory diseases claim 54 , tissue or organ transplant rejections claim 54 , graft versus host disease (GVHD) claim 54 , multiple organ injury syndromes claim 54 , acute glomerulonephritis claim 54 , reactive arthritis claim 54 , hereditary emphysema claim 54 , chronic obstructive pulmonary disease (COPD) claim 54 , cystic fibrosis claim 54 , adult respiratory distress syndrome (ARDS) claim 54 , ischemic-reperfusion injury claim 54 , stroke claim 54 , rheumatoid arthritis (RA) claim 54 , osteoarthritis (OA) claim 54 , asthma claim 54 , allergic rhinitis claim 54 , lupus nephritis claim 54 , Crohn's disease claim 54 , ulcerative colitis claim 54 , necrotizing enterocolitis claim 54 , pancreatitis claim 54 , pneumonia (PCP) claim 54 , inflammatory bowel disease (IBD) claim 54 , severe acute respiratory syndrome (SARS) claim 54 , ...

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Номер записи: 53
05-12-2013 дата публикации

POLYMORPHS OF (S)-1-(4,4,6,6,6-PENTADEUTERO-5-HYDROXYHEXYL)-3-7-DIMETHYL-1H-PURINE-2,6(3H,7H)-DIONE

Номер: US20130324564A1
Автор: Bis Joanna A., IGO David H., Turnquist David J.
Принадлежит: CONCERT PHARMACEUTICALS, INC.

The present invention provides individual crystalline polymorphs of (S)-1-(4,4,6, 6,6-pentadeutero-5-hydroxy-hexyl)-3,7-dimethyl-1H-purine-2,6(3H,7H)-dione designated Form 1, Form 2, Form 3 and Form 4. Each polymorph disclosed herein is characterized according to one or more of (a) powder X-ray diffraction data (“XRPD”); (b) differential scanning calorimetry (“DSC”); and (e) thermo gravimetric analysis (TGA). 1. Form 1 polymorph of (S)-1-(4 ,4 ,6 ,6 ,6-pentadeutero-5-hydroxyhexyl)-3 ,7-dimethyl-1H-purine-2 ,6(3H ,7H)-dione characterized by at least one of:a. a powder X-ray diffraction pattern having two or more peaks expressed in degrees 2-theta±0.2° and selected from 9.3, 13.4, 18.8, 19.7, 21.8, 22.9, 23.8, and 29.5 degrees; orb. an endotherm at 110.7±4° C.;2. The polymorph of claim 1 , characterized by a powder X-ray diffraction having peaks expressed in degrees 2-theta±0.2° at each of 9.3 claim 1 , 13.4 claim 1 , 18.8 claim 1 , 19.7 claim 1 , 21.8 claim 1 , 22.9 claim 1 , 23.8 claim 1 , and 29.5 degrees.3. The polymorph of claim 2 , characterized by a powder X-ray diffraction having peaks expressed in degrees 2-theta±0.2° at each of 9.3 claim 2 , 10.5 claim 2 , 11.9 claim 2 , 13.4 claim 2 , 15.5 claim 2 , 16.1 claim 2 , 18.7 claim 2 , 18.8 claim 2 , 19.7 claim 2 , 21.8 claim 2 , 22.9 claim 2 , 23.8 claim 2 , 24.3 claim 2 , 27.0 claim 2 , and 29.5 degrees.4. The polymorph of having at least 98% deuterium incorporation at each of the C4′ and C6′ positions claim 1 , as determined by 1H-NMR.5. The polymorph of wherein the polymorph is substantially free of (S)-1-(4 claim 1 ,4 claim 1 ,6 claim 1 ,6 claim 1 ,6-pentadeutero-5-hydroxyhexyl)-3 claim 1 ,7-dimethyl-8-deutero-1H-purine-2 claim 1 ,6(3H claim 1 ,7H)-dione as determined by H-NMR.6. Form 2 polymorph of (S)-1-(4 claim 1 ,4 claim 1 ,6 claim 1 ,6 claim 1 ,6-pentadeutero-5-hydroxyhexyl)-3 claim 1 ,7-dimethyl-1H-purine-2 claim 1 ,6(3H claim 1 ,7H)-dione characterized by at least one of:a. a powder X-ray diffraction ...

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Номер записи: 54
05-12-2013 дата публикации

METHODS FOR THE SYNTHESIS OF 1,3-SUBSTITUTED AMINOURACILS AND OTHER XANTHINE-RELATED COMPOUNDS

Номер: US20130324724A1
Автор: Diep Nhut, Kalyan Yuriy B.
Принадлежит:

Methods for the synthesis of disubstituted aminouracils and xanthine and/or xanthine-related compounds are provided. 2. The process according to claim 1 , wherein the alkoxide is a metal alkoxide selected from the group consisting of potassium tert-butoxide claim 1 , sodium ethoxide claim 1 , potassium ethoxide claim 1 , calcium ethoxide claim 1 , sodium tert-butoxide and combinations thereof.3. The process according to claim 2 , wherein the metal alkoxide is sodium ethoxide.4. The process according to claim 1 , wherein step b) is performed at a temperature of about 0° C. to about 100° C.5. The process according to claim 4 , wherein step b) is performed at a temperature of about 40° C.6. The process according to claim 1 , wherein step b) further includes an organic solvent selected from the group consisting of dimethylformamide claim 1 , toluene claim 1 , xylene and combinations thereof.7. The process according to claim 1 , wherein the copper catalyst is selected from the group consisting of copper bromide claim 1 , copper iodide claim 1 , copper acetate claim 1 , copper chloride claim 1 , copper carbonate claim 1 , copper nitrate claim 1 , copper sulfate claim 1 , copper hydroxide claim 1 , copper methylate and combinations thereof.8. The process according to claim 7 , wherein the copper catalyst comprises copper acetate.9. The process according to claim 1 , wherein the first metal carbonate is selected from the group consisting of sodium carbonate claim 1 , potassium carbonate claim 1 , lithium carbonate claim 1 , cesium carbonate claim 1 , sodium bicarbonate claim 1 , potassium bicarbonate claim 1 , lithium bicarbonate claim 1 , cesium bicarbonate and combinations thereof.10. The process according to claim 9 , wherein the first metal carbonate is sodium carbonate.11. The process according to claim 1 , wherein the second metal carbonate is selected from the group consisting of sodium carbonate claim 1 , potassium carbonate claim 1 , lithium carbonate claim 1 , ...

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Номер записи: 55
19-12-2013 дата публикации

Carbocycle-Substituted Purine And 7-Deazapurine Compounds

Номер: US20130338173A1
Автор: Chesworth Richard, Kuntz Kevin W., Olhava Edward J.
Принадлежит: EPIZYME, INC.

The present invention relates to carbocycle-substituted purine and 7-deazapurine compounds. The present invention also relates to pharmaceutical compositions containing these compounds and methods of treating disorders in which DOT1-mediated protein methylation plays a part, such as cancer and neurological disorders, by administering these compounds and pharmaceutical compositions to subjects in need thereof. 20. The compound of claim , wherein at least one of m and n is 2.4. The compound of claim 1 , wherein each of G and J is independently OR claim 1 , in which Ris H.5. (canceled)6. The compound of claim 1 , wherein Lis N(Y) claim 1 , SO or SO.7. (canceled)8. The compound of claim 1 , wherein Y is R claim 1 , in which Ris C-Calkyl.9. (canceled)10. The compound of claim 1 , wherein Lis absent.11. (canceled)12. The compound of claim 1 , wherein at least one of R claim 1 , R claim 1 , R claim 1 , and Ris halo claim 1 , C-Calkoxyl optionally substituted with one or more halo claim 1 , C-Calkylsulfonyl optionally substituted with one or more halo claim 1 , or C-Calkyl optionally substituted with one or more halo.13. The compound of claim 1 , wherein at least one of R claim 1 , R claim 1 , R claim 1 , and Ris selected from the group consisting of F claim 1 , Cl claim 1 , CF claim 1 , OCF claim 1 , SOCF claim 1 , C-Calkyl claim 1 , and C-Calkoxyl.14. The compound of claim 1 , wherein Ris H or C-Calkyl.1518-. (canceled)19. The compound of claim 1 , wherein E is -M-T claim 1 , Mbeing a bond or C-Calkyl linker claim 1 , Tbeing phenyl claim 1 , naphthyl claim 1 , thienyl claim 1 , cyclopropyl claim 1 , or cyclohexyl claim 1 , and Tbeing optionally substituted with one or more substituents selected from the group consisting of halo claim 1 , hydroxyl claim 1 , thiol claim 1 , carboxyl claim 1 , cyano claim 1 , nitro claim 1 , C-Calkyl claim 1 , C-Calkenyl claim 1 , C-Calkynyl claim 1 , C-Calkoxyl claim 1 , C-Chaloalkyl claim 1 , C-Chaloalkoxyl claim 1 , C-Calkylthio claim 1 , ...

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Номер записи: 56
26-12-2013 дата публикации

CERTAIN CHEMICAL ENTITIES, COMPOSITIONS AND METHODS

Номер: US20130345216A1
Автор: Chan Katrina, Li Liansheng, Liu Yi, Ren Pingda, Rommel Christian, Wilson Troy Edward
Принадлежит: INTELLIKINE LLC

Chemical entities that modulate PI3 kinase activity, pharmaceutical compositions containing the chemical entities, and methods of using these chemical entities for treating diseases and conditions associated with PI3 kinase activity are described herein. 3. The compound of claim 2 , wherein Wis aryl.4. The compound of claim 3 , wherein Wis phenyl.5. The compound of claim 2 , wherein Wis cyclopropyl.6. The compound of claim 2 , wherein Wis substituted by at least one of —CH claim 2 , —CHCH claim 2 , —CF claim 2 , —Cl or —F.7. The compound of claim 1 , wherein Ris hydrogen claim 1 , alkyl claim 1 , alkenyl claim 1 , alkynyl claim 1 , cycloalkyl claim 1 , heterocycloalkyl claim 1 , alkoxy claim 1 , amido claim 1 , amino claim 1 , alkoxycarbonyl sulfonamido claim 1 , halo claim 1 , cyano claim 1 , hydroxy or nitro.8. The compound of claim 1 , wherein Ris —H claim 1 , —CH claim 1 , —CHCH claim 1 , —CF claim 1 , —Cl or —F.9. The compound of claim 1 , wherein Ris —CHor —Cl.10. The compound of claim 1 , wherein Ris —CH.11. The compound of claim 1 , wherein Ris —CH—CH.13. The compound of claim 12 , wherein Ris —H.16. The compound of claim 14 , wherein Ris H.17. The compound of claim 14 , wherein Ris halo.1817. A pharmaceutical composition comprising a compound of - and a pharmaceutically acceptable excipient.1917. A method of inhibiting a phosphatidyl inositol-3 kinase (PI3 kinase) claims 1 , comprising: contacting the PI3 kinase with an effective amount of a compound of -.2017. A method of inhibiting a phosphatidyl inositol-3 kinase (PI3 kinase) present in a cell claims 1 , comprising; contacting said cell with an effective amount of a compound of -.21. The method of wherein the inhibition takes place in a subject suffering from a disorder selected from the group consisting of cancer claim 19 , bone disorder claim 19 , inflammatory disease claim 19 , immune disease claim 19 , nervous system disease claim 19 , metabolic disease claim 19 , respiratory disease claim 19 , ...

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Номер записи: 57
26-12-2013 дата публикации

HETEROARYL COMPOUNDS USEFUL AS INHIBITORS OF E1 ACTIVATING ENZYMES

Номер: US20130345242A1
Автор: Claiborne Christopher F., CRITCHLEY Stephen, Cullis Courtney A., Langston Steven P., Mizutani Hirotake, Olhava Edward J., Peluso Stephane, Visiers Irache, Vyskocil Stepan, Weatherhead Gabriel S.
Принадлежит: Millennium Pharmaceuticals, Inc.

This invention relates to compounds that inhibit E1 activating enzymes, pharmaceutical compositions comprising the compounds, and methods of using the compounds. The compounds are useful for treating disorders, particularly cell proliferation disorders, including cancers, inflammatory and neurodegenerative disorders; and inflammation associated with infection and cachexia. 119-. (canceled)22. (canceled)23. (canceled)24. A pharmaceutical composition claim 20 , comprising a compound of and a pharmaceutically acceptable carrier.25. The pharmaceutical composition of claim 24 , formulated for administration to a human patient.26. A method of decreasing an E1 enzyme activity in a sample claim 20 , comprising contacting the sample with a compound of .27. The method of claim 26 , wherein the E1 enzyme is selected from the group consisting of NAE claim 26 , UAE claim 26 , and SAE.28. The method of claim 27 , wherein the E1 enzyme is NAE.29. A method for treating cancer in a patient in need thereof claim 20 , comprising administering to the patient a compound of .30. The method of claim 29 , wherein the cancer is lung cancer claim 29 , colorectal cancer claim 29 , ovarian cancer claim 29 , or a hematological cancer.31. A method for treating an immune response disorder or vascular cell proliferation disorder in a patient in need thereof claim 20 , comprising administering to the patient a compound of .32. A compound of claim 20 , selected fromI-3 [(1R,2R,3S,4R)-2,3-dihydroxy-4-(9H-purin-6-ylamino)cyclopentyl]methyl sulfamate;I-9 {(1R,2R,3S,4R)-2,3-dihydroxy-4-[8-phenyl-9H purin-6-yl)amino]cyclopentyl}-methyl sulfamate;I-34 ((1S,2S,4R)-4-{[8-(2-chlorophenyl)-9H-purin-6-yl]amino}-2-hydroxycyclopentyl)methyl sulfamate;I-36 {(1S,2S,4R)-2-hydroxy-4-[(7-methyl-8-phenyl-7H-purin-6-yl)-amino]cyclopentyl}methyl sulfamate;I-37 ((1S,2S,4R)-2-hydroxy-4-{[8-(2-phenoxyphenyl)-9H-purin-6-yl]amino}-cyclopentyl)methyl sulfamate;I-38 {(1S,2S,4R)-2-hydroxy-4-[(6-phenyl-7H-pyrrolo[2,3-d]pyrimidin ...

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Номер записи: 58
02-01-2014 дата публикации

BENZOIMIDAZOLES AS PROLYL HYDROXYLASE INHIBITORS

Номер: US20140005193A1
Автор: Hocutt Frances Meredith, JR. BARRY EASTMAN, LEONARD, Peltier Hillary M., Phuong Victor K., Rabinowitz Michael H., Rosen Mark D., Tarantino Kyle T., Venkatesan Hariharan, Zhao Lucy Xiumin
Принадлежит: Janssen Pharmaceutica NV

The present invention is directed to benzoimidazole compounds of the formula: 2. A compound of claim 1 , where Rand Rare each —H.3. A compound of wherein each Ris independently selected from the group consisting of H claim 1 , halo claim 1 , —CF claim 1 , —OCF claim 1 , phenyl (optionally substituted or unsubstituted with up to three —CF claim 1 , halo claim 1 , —OH claim 1 , Calkyl claim 1 , Calkoxy claim 1 , and —OCF) claim 1 , phenoxy (optionally substituted or unsubstituted with up to three halo claim 1 , Calklyl claim 1 , Calkoxy claim 1 , and —OCF) claim 1 , benzyloxy-phenyl (optionally substituted or unsubstituted with up to three halo) claim 1 , benzyloxy claim 1 , benzyloxymethyl claim 1 , phenylsulfanyl (optionally substituted or unsubstituted with up to three —Calkyl claim 1 , halo claim 1 , —CF claim 1 , —OCF claim 1 , and —Calkoxy) claim 1 , benzylsulfanyl (optionally substituted or unsubstituted with up to three halo claim 1 , Calkyl claim 1 , Ccycloalkylmethyl claim 1 , —CF claim 1 , and —OCF) claim 1 , phenethylsulfanyl claim 1 , benzenesulfonyl (optionally substituted or unsubstituted with up to three Calkyl claim 1 , Calkoxy claim 1 , halo claim 1 , —CF claim 1 , and —OCF) claim 1 , phenylmethanesulfonyl (optionally substituted or unsubstituted with up to three Calkyl claim 1 , Calkoxy claim 1 , halo claim 1 , Ccycloalkylmethyl claim 1 , —CF claim 1 , and —OCF) claim 1 , phenyl-ethanesulfonyl claim 1 , benzenesulfinyl claim 1 , cyano-biphenyl-4-ylmethylsulfanyl claim 1 , cyano-biphenyl-4-ylmethanesulfonyl claim 1 , phenylcarbamoyl claim 1 , benzylcarbamoyl claim 1 , benzylamino claim 1 , phenylsulfamoyl claim 1 , phenylamino claim 1 , benzoylamino claim 1 , and benzenesulfonylamino.4. A compound of claim 1 , where two adjacent Rgroups are joined to form an optionally substituted 3-8 membered ring containing one or more O claim 1 , S or N.5. A compound of wherein said optionally substituted 3-8 membered ring is aromatic.6. A compound of claim 1 , ...

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Номер записи: 59
02-01-2014 дата публикации

RAF KINASE MODULATORS AND METHODS OF USE

Номер: US20140005198A1
Автор: Doherty Elizabeth M., HUANG Qi, Liu Gang, SMITH Adrian L.
Принадлежит: Amgen Inc.

The present invention comprises a new class of compounds capable of modulating the activity of Raf kinase and, accordingly, useful for treatment of Raf kinase mediated diseases, including melanomas, tumors and other cancer-related conditions. The compounds have a general Formula I 3. The compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Ais C claim 1 , Ais N and bond B is a double bond.5. The compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein each of A claim 1 , Aand A claim 1 , independently claim 1 , is CH and Ais N.6. The compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein each of A claim 1 , Aand A claim 1 , independently claim 1 , is CRwherein each R claim 1 , independently claim 1 , is H claim 1 , halo claim 1 , haloalkyl claim 1 , NO claim 1 , CN claim 1 , C-alkyl claim 1 , C-alkenyl claim 1 , C-alkynyl claim 1 , C-cycloalkyl claim 1 , NRR claim 1 , OR claim 1 , SRor C(O)Rand Ris H claim 1 , C-alkyl or C-haloalkyl.7. The compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein X is CH claim 1 , NH claim 1 , O or S.8. The compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris NRR claim 1 , NRR claim 1 , NRC(O)R claim 1 , NRC(O)R claim 1 , NRS(O)Ror NRS(O)R;{'sup': 5', '7, 'sub': 1-6', '3-6, 'Ris H, C-alkyl or C-cycloalkyl optionally substituted with 1-3 substituents of R; and'}{'sup': 6', '7, 'Ris phenyl, naphthyl, pyridyl, pyrimidinyl, triazinyl, pyridazinyl, thiophenyl, furyl, tetrahydrofuryl, pyrrolyl, pyrazolyl, quinolinyl, isoquinolinyl, quinazolinyl, isoquinazolinyl, phthalazinyl, thieno-pyrazolyl, imidazolyl, triazolyl, thiazolyl, thiadiazolyl, oxazolyl, oxadiazolyl, isoxazolyl, isothiazolyl, benzoxazolyl, benzothiazolyl, benzoxadiazolyl, indolyl, azaindolyl, isoindolyl, indazolyl, benzofuranyl, benzothiophenyl, benzimidazolyl, pyrrolidinyl, pyrazolinyl, morpholinyl, piperidinyl or ...

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Номер записи: 60
02-01-2014 дата публикации

COMPOSITIONS USEFUL FOR TREATING DISORDERS RELATED TO TRPA1

Номер: US20140005208A1
Автор: Hang Jianfeng, Ng Howard
Принадлежит: HYDRA BIOSCIENCES, INC.

Compounds and compositions for treating disorders related to TRPA1 are described herein. 110-. (canceled)12. The method of claim 11 , wherein the composition contains an enantiomeric excess of at least 50% of a compound of Formula I.13. The method of claim 11 , wherein the composition contains an enantiomeric excess of at least 75% of a compound of Formula I.14. The method of claim 11 , wherein the composition contains an enantiomeric excess of at least 90% of a compound of Formula I.15. The method of claim 11 , wherein the composition contains an enantiomeric excess of at least 95% of a compound of Formula I.16. The method of claim 11 , wherein the composition contains an enantiomeric excess of at least 99% of a compound of Formula I.17. The method of claim 11 , wherein the composition contains a pharmaceutically acceptable salt of the compound of Formula I.18. The method of claim 17 , wherein the pharmaceutically acceptable salt is a hydrochloride claim 17 , hydrobromide claim 17 , sulfate claim 17 , or phosphate salt of a compound of Formula I.19. The method of claim 11 , comprising treating the human for chronic pain.20. The method of claim 11 , comprising treating the human for acute pain. This application claims priority to U.S. Ser. No. 61/139,884, filed Dec. 22, 2008, the entire contents of which is incorporated herein by reference.The invention relates to compounds and compositions useful for treating disorders related to TRPA1.A variety of ion channel proteins exist to mediate ion flux across cellular membranes. The proper expression and function of ion channel proteins is essential for the maintenance of cell function and intracellular communication. Numerous diseases are the result of misregulation of membrane potential or aberrant calcium handling. Given the central importance of ion channels in modulating membrane potential and ion flux in cells, identification of agents that can promote or inhibit particular ion channels are of great interest, both as ...

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Номер записи: 61
16-01-2014 дата публикации

Irak inhibitors and uses thereof

Номер: US20140018361A1
Автор: Craig E. Masse, Donna L. Romero, Geraldine C. Harriman, Jeremy Robert Greenwood, Matthew David Wessel, Shaughnessy Robinson
Принадлежит: Nimbus Iris Inc

The present invention provides furano- and pyrrolo-pyrimidine and pyridine compounds, compositions thereof, and methods of using the same.

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Номер записи: 62
30-01-2014 дата публикации

6-ETHER/THIOETHER-PURINES AS TOPOISOMERASE II CATALYTIC INHIBITORS AND THEIR USE IN THERAPY

Номер: US20140031539A1
Автор: JENSEN Lars Hollund, SEHESTED Maxwell
Принадлежит: Biocodex, Inc

The present invention relates to certain purines, which act as topoisomerase II catalytic inhibitors. These compounds are useful in combination with topoisomerase II poisons, such as anthracyclines and epipodophyllotoxins, in the treatment of proliferative conditions (e.g., cancer). These compounds are useful in the treatment of tissue damage associated with extravasation of a topoisomerase II poison, such as an anthracycline or an epipodophyllotoxin. 2104.-. (canceled) This application is related to: United Kingdom patent application 0502573.9 filed 8 Feb. 2005, the contents of which are incorporated herein by reference in their entirety.The present invention relates to topoisomerase II catalytic inhibitors, and their use in therapy. In particular, the present invention relates to certain purines (6-ether/thioether-purines) and derivatives thereof for use in combination with cytostatic agents that act as topoisomerase II poisons, such as anthracyclines and epipodophyllotoxins, in the treatment of proliferative conditions (e.g., cancer). The present invention also relates to use of these compounds in the treatment of tissue damage associated with accidental extravasation of a topoisomerase II poison, such as an anthracycline or an epipodophyllotoxin.A number of patents and publications are cited herein in order to more fully describe and disclose the invention and the state of the art to which the invention pertains. Each of these references is incorporated herein by reference in its entirety into the present disclosure, to the same extent as if each individual reference was specifically and individually indicated to be incorporated by reference.Throughout this specification, including the claims which follow, unless the context requires otherwise, the word “comprise,” and variations such as “comprises” and “comprising,” will be understood to imply the inclusion of a stated integer or step or group of integers or steps but not the exclusion of any other integer or ...

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Номер записи: 63
13-02-2014 дата публикации

Pyrazine derivatives as fgfr inhibitors

Номер: US20140045814A1
Автор: Chunhong He, LIANG Lu, Wenqing Yao
Принадлежит: Incyte Corp

The present invention relates to pyrazine derivatives, and pharmaceutical compositions including the same, that are inhibitors of one or more FGFR enzymes and are useful in the treatment of FGFR-associated diseases such as cancer.

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Номер записи: 64
13-02-2014 дата публикации

METHOD FOR PRODUCING COMPLEX CRYSTAL AND METHOD FOR SCREENING COMPLEX CRYSTAL

Номер: US20140045824A1
Автор: Fukuda Mamoru, Goto Akinori
Принадлежит:

The present invention relates to a method for producing a complex crystal composed of two or more different compounds, comprising crystallizing the two or more different compounds under a condition at which menthol is heat melted, and a method for screening a complex crystal. In accordance with the method for producing a complex crystal of the present invention, a complex crystal capable of being used as a drug material can be produced rapidly, simply and efficiently. In addition, in accordance with the method for screening a complex crystal of the present invention, a stable complex crystal can be searched, which is industrially useful. 1. A method for producing a complex crystal composed of two or more different compounds , comprising crystallizing the two or more different compounds under a condition at which menthol is heat melted.2. A method for producing a complex crystal , comprising the following steps (i) and (ii):(i) a step of preparing a mixture composed of two or more different compounds and menthol, and(ii) a step of heat melting the menthol contained in the mixture.3. A method for screening a complex crystal , comprising the following steps (I) and (II):(I) a step of preparing plural mixtures each containing two or more different compounds and menthol, and(II) a step of heat melting the menthol contained in the mixture.4. A method for producing a complex crystal composed of two or more different compounds and water , comprising crystallizing the two or more different compounds under a humidified condition and under a condition at which menthol is heat melted.5. The method according to claim 1 , comprising a step of subsequently evaporating the heat melted menthol.6. The method according to claim 1 , wherein the content of each of the two or more different compounds contained in the mixture is an equimolar amount in the mixture.7. The method according to claim 1 , wherein the complex crystal is a cocrystal.8. The method according to claim 2 , comprising ...

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Номер записи: 65
13-02-2014 дата публикации

PURINE-BASED TRIAZOLES

Номер: US20140045866A1
Автор: Kudo Wataru, Nair Nanditha G., Reddy Prakash, Smith Mark A.
Принадлежит:

A pharmaceutical composition for inhibiting at least protein kinase in a cell of a subject includes a purine based triazole. 2. The compound of claim 2 , where Ris a fluorinated aryl claim 2 , cyclic claim 2 , or heterocyclic group.3. The compound of claim 3 , where Rand Rare each independently a hydrogen claim 3 , a halogen claim 3 , C-Calkyl claim 3 , C-Calkenyl claim 3 , C-Calkynyl claim 3 , C-Caryl claim 3 , C-Calkaryl claim 3 , C-Caralkyl claim 3 , or an R—NH— claim 3 , R—NH—NH— claim 3 , NH—R′—NH— or R—NH—R′—NH— radical claim 3 , in which Rrepresents a straight- or branched-chain claim 3 , saturated or unsaturated alkyl radical claim 3 , an aryl or cycloalkyl radical or a heterocyclic ring and R′ represents a straight- or branched-chain claim 3 , saturated or unsaturated alkylene group or an arylene or cycloalkylene group claim 3 , R4 and R′ each containing 1 to 8 carbon atoms claim 3 , and where each Rand Rbeing independently unsubstituted or substituted claim 3 , where appropriate claim 3 , by one or more —OH claim 3 , halogen claim 3 , amino or alkyl groups.6. The compound of claim 6 , where Ris Cl claim 6 , F claim 6 , an alkyl or substituted alkyl.11. A pharmaceutical composition comprising a compound according to claim 1 , admixed with a pharmaceutically acceptable diluent claim 1 , excipient claim 1 , carrier or mixtures thereof.1228-. (canceled)29. A method for promoting neuron survival in the presence of amyloid β claim 1 , the method comprising:{'claim-ref': {'@idref': 'CLM-00001', 'claim 1'}, 'administering to a neuron in the presence of amyloid β a therapeutically effective amount of a compound according to .'}30. A method for treating a neurological disorder in a subject claim 1 , the method comprising:{'claim-ref': {'@idref': 'CLM-00001', 'claim 1'}, 'administering to the subject a therapeutically effective amount of a compound according to , and a pharmaceutical carrier.'}3126. The method of claim claim 1 , the neurological disorder being ...

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Номер записи: 66
13-02-2014 дата публикации

HSP90 Inhibitors

Номер: US20140045867A1
Автор: Chiosis Gabriela, Taldone Tony
Принадлежит: Sloan-Kettering Institute for Cancer Research

The disclosure relates to Compounds of Formula (1) : 2. The compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Xis dimethylamine.3. The compound of or claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris neopentyl.4. The compound of or claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris isopropyl.5. The compound of or claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris t-butyl.6. The compound of any of to or a pharmaceutically acceptable salt thereof claim 1 , wherein Z claim 1 , Zand Zare each N.7. The compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Z claim 1 , Zand Zare each N claim 1 , Xis dimethlyamine claim 1 , Y is S claim 1 , Ris ethylene claim 1 , Ris neopentyl claim 1 , and X claim 1 , is H.8. The compound of or a pharmaceutically acceptable salt thereof claim 1 , wherein Z claim 1 , Zand Zare each N claim 1 , Xis dimethlyamine claim 1 , Y is S claim 1 , Ris propylene claim 1 , Ris isopropyl claim 1 , and Xis H.9. The compound of or a pharmaceutically acceptable salt thereof claim 1 , wherein Z claim 1 , Zand Zare each N claim 1 , Xis dimethlyamine claim 1 , Y is S claim 1 , Ris propylene claim 1 , Ris t-butyl claim 1 , and Xis H.109. A pharmaceutical composition comprising the compound as in one of - claims 1 , or a pharmaceutically acceptable salt thereof claims 1 , and a pharmaceutically acceptable carrier.119. A method for treating or preventing cancer or a neurodegenerative disorder claims 1 , comprising administering to a patient in need thereof a therapeutically effective amount of a compound as in one of -.129. Use of a compound as in one of - in formulating a pharmaceutical composition for the treatment or prevention of cancer or a neurodegenerative disorder.139. A method for the inhibition of Hsp90 claims 1 , comprising contacting Hsp90 with an Hsp90 function inhibiting amount of a compound as in one ...

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Номер записи: 67
13-02-2014 дата публикации

Method of utilizing recycled deuterium oxide in the synthesis of deuterated compounds

Номер: US20140046060A1
Автор: Andrew D. Jones, Bernhard J. Paul
Принадлежит: Concert Pharmaceuticals Inc

The present invention provides a method for utilizing recycled deuterium oxide synthesis of deuterated compounds.

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Номер записи: 68
27-02-2014 дата публикации

XANTHINE DERIVATIVES, THE PREPARATION THEREOF AND THEIR USE AS PHARMACEUTICAL COMPOSITIONS

Номер: US20140057901A1
Автор: ECKHARDT Matthias, Himmelsbach Frank, LANGKOPF Elke, LOTZ Ralf, MAIER Roland, MARK Michael
Принадлежит: Boehringer Ingelheim Pharma GmbH & Co. KG

The present invention relates to substituted xanthines of general formula 2. The Compound according to claim 1 , wherein{'sup': '1', 'claim-text': (1) a hydrogen atom,', {'sub': '1-6', '(2) a C-alkyl group,'}, {'sub': '3-6', '(3) a C-alkenyl group,'}, {'sub': 3-4', '1-2, '(4) a C-alkenyl group which is substituted by a C-alkyloxy-carbonyl group,'}, {'sub': '3-6', '(5) a C-alkynyl group,'}, {'sub': 3-6', '1-3, '(6) a C-cycloalkyl-C-alkyl group,'}, '(7) a phenyl group which may be substituted by a fluorine, chlorine or bromine atom or by a methyl, trifluoromethyl, hydroxy or methoxy group,', {'sub': '1-4', 'sup': 10', '12, 'claim-text': [{'sup': '10', 'claim-text': (i) a hydrogen atom, a fluorine, chlorine or bromine atom,', {'sub': 1-4', '3-6, '(ii) a C-alkyl, trifluoromethyl, hydroxymethyl, C-cycloalkyl, ethynyl or phenyl group,'}, {'sub': 1-4', '1-2', '1-2', '1-3', '1-3', '1-3', '1-3', '1-2', '1-3', '1-2', '1-3', '1-3', '1-3', '1-3', '3-6', '3-6', '1-2, '(iii) a hydroxy, C-alkyloxy, difluoromethoxy, trifluoromethoxy, 2,2,2-trifluoroethoxy, phenoxy, benzyloxy, 2-propen-1-yloxy, 2-propyn-1-yloxy, cyano-C-alkyloxy, C-alkylsulphonyloxy, phenylsulphonyloxy, carboxy-C-alkyloxy, C-alkyloxy-carbonyl-C-alkyloxy, aminocarbonyl-C-alkyloxy, C-alkyl-aminocarbonyl-C-alkyloxy, di-(C-alkyl)aminocarbonyl-C-alkyloxy, pyrrolidin-1-yl-carbonyl-C-alkyloxy, piperidin-1-ylcarbonyl-C-alkyloxy, morpholin-4-ylcarbonyl-C-alkyloxy, methylsulphanylmethoxy, methylsulphinylmethoxy, methylsulphonylethoxy, C-cycloalkyloxy or C-cycloalkyl-C-alkyloxy group,'}, {'sub': 1-3', '1-3', '1-3', '1-3', '1-2', '1-2, '(iv) a carboxy, C-alkyloxycarbonyl, carboxy-C-alkyl, C-alkyloxy-carbonyl-C-alkyl, aminocarbonyl, C-alkylaminocarbonyl, di-(C-alkyl)aminocarbonyl or cyano group,'}, {'sub': 1-2', '1-2', '1-2', '1-2', '1-2', '1-2', '1-2', '1-2', '1-2', '1-3', '1-2', '1-2', '1-2', '1-2', '1-2', '1-2', '1-2, '(v) a nitro, amino, C-alkylamino, di-(C-alkyl)amino, cyano-C-alkylamino, [N-(cyano-C-alkyl)-N—C-alkyl-amino ...

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Номер записи: 69
27-02-2014 дата публикации

Inhibitors of PI3K-Delta and Methods of Their Use and Manufacture

Номер: US20140058103A1
Автор: Patrick Kearney
Принадлежит: Exelixis Inc

The invention is directed to Compounds of Formula I: and pharmaceutically acceptable salts or solvates thereof, as well as methods of making and using the compounds.

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Номер записи: 70
06-03-2014 дата публикации

THERAPIES FOR HEMATOLOGIC MALIGNANCIES

Номер: US20140066386A1
Автор: Gallatin W. Michael, Giese Neill A., Ulrich Roger G.
Принадлежит: Gilead Calistoga LLC

The invention provides methods that relate to a novel therapeutic strategy for the treatment of hematological malignancies and inflammatory diseases. In particular, the method comprises administration of a compound of formula A, 141-. (canceled)43. The method according to claim 42 , wherein said hematological malignancy is leukemia or lymphoma.44. The method according to claim 42 , wherein said hematological malignancy is selected from the group consisting of mantle cell lymphoma (MCL) claim 42 , multiple myeloma (MM) claim 42 , chronic lymphocytic leukemia (CLL) claim 42 , non-Hodgkin's lymphoma (NHL) claim 42 , acute lymphocytic leukemia (ALL) claim 42 , acute myeloid leukemia (AML) claim 42 , small lymphocytic lymphoma (SLL) claim 42 , follicular lymphoma claim 42 , Waldenstrom's macroglobulinemia (WM) claim 42 , and B-cell lymphoma and diffuse large B-cell lymphoma (DLBCL).45. The method according to claim 42 , wherein the subject is refractory to chemotherapy treatment or is in relapse after treatment with chemotherapy.46. The method according to claim 42 , further comprising administering at least one additional therapeutic agent.47. The method according to claim 42 , comprising administering to said subject a pharmaceutical composition comprising the compound of formula I″ or a pharmaceutically acceptable salt thereof claim 42 , and at least one pharmaceutically acceptable excipient.48. The method according to claim 42 , wherein said subject has at least one enlarged lymph node.49. The method according to claim 45 , wherein said subject is refractory to at least two standard or experimental chemotherapy treatments.50. The method according to claim 42 , wherein said compound of formula I″ or a pharmaceutically acceptable salt thereof is administered at a dose of 50-350 mg BID.51. The method according to claim 50 , wherein said compound of formula I″ or a pharmaceutically acceptable salt thereof is administered at a dose of 150 mg BID. This application claims ...

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Номер записи: 71
06-03-2014 дата публикации

PURINE NUCLEOSIDE MONOPHOSPHATE PRODRUGS FOR TREATMENT OF CANCER AND VIRAL INFECTIONS

Номер: US20140066395A1
Автор: Cho Jong Hyun, Coats Steven J., SCHINAZI RAYMOND F., Zhang Hongwang, ZHOU Longhu
Принадлежит:

The present invention is directed to compounds, compositions and methods for treating or preventing cancer and viral infections, in particular, HIV, HCV, Norovirus, Saporovirus, HSV-1, HSV-2, Dengue virus, Yellow fever, and HBV in human patients or other animal hosts. The compounds are certain 6-substituted purine monophosphates, and pharmaceutically acceptable, salts, prodrugs, and other derivatives thereof. In particular, the compounds show potent antiviral activity against HIV-1, HIV-2, HCV, Norovirus, Saporovirus, HSV-1, HSV-2, Dengue virus, Yellow fever, and HBV. 2. The compound of claim 1 , wherein Rselected from the group consisting of H claim 1 , F claim 1 , Cl claim 1 , Br claim 1 , I claim 1 , OH claim 1 , SH claim 1 , NH claim 1 , NHOH claim 1 , NHNH claim 1 , C(O)OH claim 1 , CN claim 1 , C(O)NH claim 1 , C(S)NH claim 1 , C(O)OR claim 1 , R claim 1 , OR claim 1 , SR claim 1 , SSR claim 1 , NHR claim 1 , and NR.3. The compounds of claim 1 , wherein Ris selected from the group consisting of NH claim 1 , dimethylamine claim 1 , methyl-allyl-amine claim 1 , methoxy claim 1 , chloro claim 1 , cyclopropylamine claim 1 , 5-hydroxy-pentylamine claim 1 , 1 claim 1 ,1-dimethyl-ethanolamine claim 1 , and 2-methoxy-ethylamine.4. The compounds of claim 1 , wherein the compounds are in the β-L- or β-D configuration claim 1 , or a racemic mixture thereof.5. A method for treating a host infected with HIV-1 or HIV-2 claim 1 , preventing an HIV-1 or HIV-2 infection claim 1 , or reducing the biological activity of an HIV-1 or HIV-2 infection in a host claim 1 , comprising administering an effective amount of a compound of to a patient in need of treatment thereof.6. The method of claim 5 , wherein the HIV-1 or HIV-2 infection is caused by a virus comprising a mutation selected from the group consisting of TAM mutations and the M184V mutation.7. The method of claim 5 , wherein the compound is administered in another anti-HIV agent.8. The method of claim 7 , wherein the HIV- ...

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Номер записи: 72
06-03-2014 дата публикации

PYRIMIDINE SUBSTITUTED PURINE DERIVATIVES

Номер: US20140066620A1
Автор: Mysore Harish K., Williams Meredith
Принадлежит: VERASTEM, INC.

The present invention relates to purine compounds that are useful as kinase inhibitors. More particularly, the present invention relates to purine compounds, methods for their preparation, pharmaceutical compositions containing these compounds and uses of these compounds in the treatment of proliferative conditions or disorders. These compounds may be useful as medicaments for the treatment of a number of proliferative conditions or disorders including tumours and cancers as well as other disorders or conditions related to or associated with PI3 and/or mTOR kinases. 1. (canceled) The present invention relates to purine compounds that may be useful as kinase inhibitors. More particularly, the present invention relates to 2-(morpholin-4-yl), 6-(pyrimidin-5-yl) substituted purine derivatives, methods for their preparation, pharmaceutical compositions containing these compounds and uses of these compounds in the treatment of certain kinase related disorders/conditions.The search for kinase inhibitors has proven to be a fruitful area for the development of useful pharmaceutically active substances. Kinases, which are alternatively known as phosphotransferases, are enzymes that transfer phosphate groups from high energy donor molecules (for example ATP) to specific target molecules (typically called substrates) in a process termed phosphorylation. One of the largest groups of kinases are the protein kinases which act on and modify the activity of specific proteins.As a result of this activity these kinases are involved in a number of cellular processes such as in signalling and to prime the cell for biochemical reactions in metabolism. Certain cellular signalling processes have been implicated as important in a number of medical conditions and the effective inhibition of certain cell signalling processes therefore provides the potential to stop these conditions developing. Accordingly, kinases represent an attractive target for medicinal chemists as the provision of ...

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Номер записи: 73
13-03-2014 дата публикации

SERMS for the Treatment of Estrogen Receptor-Mediated Disorders

Номер: US20140073656A1
Автор: John S. Cooperwood
Принадлежит: Florida Agricultural and Mechanical University FAMU

Novel compounds for the treatment of estrogen receptor-mediated disorders, including breast cancer, and methods of treatment using the novel compounds. The novel compounds, when administered in a safe and effective amount, present extended binding to estrogen receptors in breast tissue without activating the estrogen receptors. Estrogen is blocked from binding to the estrogen receptors for an extended period of time, effectively hindering growth of breast cancer cells.

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Номер записи: 74
27-03-2014 дата публикации

CHEMICAL COMPOUNDS, COMPOSITIONS AND METHODS FOR KINASE MODULATION

Номер: US20140088099A1
Автор: Castro Alfredo C., Chan Katrina, Evans Catherine A., Li Liansheng, Liu Yi, Ren Pingda
Принадлежит: INFINITY PHARMACEUTICALS, INC.

Chemical compounds that modulate kinase activity, including PI3 kinase activity, and chemical compounds, pharmaceutical compositions, and methods of treatment of diseases and conditions associated with kinase activity, including P13 kinase activity, are described herein. 121-. (canceled) This application claims priority from U.S. Ser. No. 61/347,370, filed May 21, 2010, which is incorporated herein by reference in its entirety.The activity of cells can be regulated by external signals that stimulate or inhibit intracellular events. The process by which stimulatory or inhibitory signals are transmitted into and within a cell to elicit an intracellular response is referred to as signal transduction. Over the past decades, cascades of signal transduction events have been elucidated and found to play a central role in a variety of biological responses. Defects in various components of signal transduction pathways have been found to account for a vast number of diseases, including numerous forms of cancer, inflammatory disorders, metabolic disorders, vascular and neuronal diseases (Gaestel et al. (2007) 14:2214-2234).Kinases represent a class of important signaling molecules. Kinases can generally be classified into protein kinases and lipid kinases, and certain kinases exhibit dual specificities. Protein kinases are enzymes that phosphorylate other proteins and/or themselves (i.e., autophosphorylation). Protein kinases can be generally classified into three major groups based upon their substrate utilization: tyrosine kinases which predominantly phosphorylate substrates on tyrosine residues (e.g., erb2, PDGF receptor, EGF receptor, VEGF receptor, src, abl), serine/threonine kinases which predominantly phosphorylate substrates on serine and/or threonine residues (e.g., mTorC1, mTorC2, ATM, ATR, DNA-PK, Akt), and dual-specificity kinases which phosphorylate substrates on tyrosine, serine and/or threonine residues.Lipid kinases are enzymes that catalyze the phosphorylation ...

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Номер записи: 75
27-03-2014 дата публикации

HSP90 Inhibitors

Номер: US20140088121A1
Автор: Chiosis Gabriela, Patel Pallav, Sun Weilin, Taldone Tony
Принадлежит: Sloan-Kettering Institute for Cancer Research

The disclosure relates to Compounds of Formulae (IA) and (IB): 8. The compound as in claim 1 , wherein Zis CH or Zis CH or Zis CH.9. The compound as in claim 1 , wherein Zand Zare each CH or Zand Zare each CH or Zand Zare each CH.10. The compound as in claim 1 , wherein Z claim 1 , Z claim 1 , and Zare each CH.11. The compound of any of to claim 1 , wherein R is interrupted by one or more —S(O)N(R)— claim 1 , —NRS(O)— claim 1 , —SON(R)— claim 1 , —NRSO— claim 1 , —C(O)N(R)— claim 1 , or —NRC(O)— groups.12. The compound of any of to claim 1 , wherein R is terminated by an —S(O)NRR claim 1 , —NRS(O)R claim 1 , —SONRR claim 1 , —NRSOR claim 1 , —C(O)NRR claim 1 , or —NRC(O)Rgroup.1310. The compound as in one of - claims 1 , wherein R is 2-ethanesulfonic acid isopropylamide claims 1 , 2-ethanesulfonic acid ethylamide claims 1 , 2-ethanesulfonic acid methylamide claims 1 , 2-ethanesulfonic acid amide claims 1 , 2-ethanesulfonic acid t-butylamide claims 1 , 2-ethanesulfonic acid isobutylamide claims 1 , 2-ethanesulfonic acid cyclopropylamide claims 1 , isopropanesulfonic acid 2-ethylamide claims 1 , ethanesulfonic acid 2-ethylamide claims 1 , N-2 ethyl methanesulfonamide claims 1 , 2-methyl-propane-2-sulfonic acid 2-ethylamide claims 1 , 2-methyl-propane-2-sulfinic acid 2-ethylamide claims 1 , 2-methyl-propane-1-sulfonic acid 2-ethylamide claims 1 , cyclopropanesulfonic acid 2-ethylamide claims 1 , 3-propane-1-sulfonic acid isopropylamide claims 1 , 3-propane-1-sulfonic acid ethylamide claims 1 , 3-propane-1-sulfonic acid methylamide claims 1 , 3-propane-1-sulfonic acid amide claims 1 , 3-propane-1-sulfonic acid t-butylamide claims 1 , 3-propane-1-sulfonic acid isobutylamide claims 1 , 3-propane-1-sulfonic acid cyclopropylamide claims 1 , propane-2-sulfonic acid 3-propylamide claims 1 , ethanesulfonic acid 3-propylamide claims 1 , N-3-propyl methanesulfonamide claims 1 , 2-methyl-propane-2-sulfonic acid 3-propylamide claims 1 , 2-methyl-propane-2-sulfinic acid 3- ...

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Номер записи: 76
03-04-2014 дата публикации

SOLID FORMS OF ANTIRETROVIRAL COMPOUNDS, PROCESS FOR THE PREPARATION AND THEIR PHARMACEUTICAL COMPOSITION THEREOF

Номер: US20140094475A1
Автор: CHAVA Satyanarayana, Gorantla Seeta R., Indukuri Venkata S., Joga Sree R., Muppidi Vamsee K.
Принадлежит: LAURUS LABS PRIVATE LIMITED

Disclosed are solid forms of antiretroviral compounds and anti-oxidative acids, and processes for their preparation. Pharmaceutical compositions using the solid forms are also disclosed. 1. A solid form comprising an antiretroviral compound and an anti-oxidative acids , wherein the antiretroviral compound is selected from the group consisting of. tenofovir , lamivudine , emtricitabine , and abacavir.2. The solid form of claim 1 , which is a salt claim 1 , a co-crystal or a polymorph of a salt or a co-crystal.3. The solid form of claim 1 , wherein the anti-oxidative acids are selected from benzoic acid derivatives or cinnamic acid derivatives.4. The solid form of claim 3 , wherein the benzoic acid derivatives are selected from p-hydroxy benzoic acid claim 3 , vanillic acid claim 3 , syringic acid claim 3 , 3 claim 3 ,4-dihydroxy benzoic acid and the like.5. The solid form of claim 3 , wherein the cinnamic acid derivatives are selected from ferulic acid claim 3 , caffeic acid claim 3 , p-coumaric acid claim 3 , sinapic acid and the like.6. The solid form of claim 1 , wherein the anti-oxidative acids are selected from the group consisting of. ferulic acid claim 1 , caffeic acid claim 1 , p-coumaric acid claim 1 , sinapic acid.7. A process for preparing a solid containing an antiretroviral compound and an anti-oxidative acid claim 1 , the process comprising the step of mixing claim 1 , in solution claim 1 , the antiretroviral compound with the anti-oxidative acid compound under crystallization conditions sufficient to produce the solid form.8. The process according to claim 7 , wherein the mixing step comprises:a) dissolving antiretroviral compound in a solvent at a temperature to produce a solution;b) combining anti-oxidative acid to the solution;c) isolating the product from the solution.9. The process according to claim 8 , wherein the solvent is selected from the group consisting of. water claim 8 , lower alcohols claim 8 , ketones claim 8 , esters claim 8 , ethers ...

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Номер записи: 77
10-04-2014 дата публикации

NEUROTROPHIN MIMETICS AND USES THEREOF

Номер: US20140100224A1
Автор: Longo Frank M., Massa Stephen M.
Принадлежит:

The present application is related to compounds which are novel neurotrophin mimetics. The application also discloses the treatment of disorders associated with p75 expression, such as degradation or dysfunction of cells expressing p75 in a mammal by administering an effective amount of such compounds. 25-. (canceled)78-. (canceled)10. (canceled)1314-. (canceled)16. A compound selected from the group consisting of(2R,3R)-2-amino-3-methyl-N-(2-morpholinoethyl)-pentanamide;(2R,3S)-2-amino-3-methyl-N-(2-morpholinoethyl)-pentanamide; and(2S,3R)-2-amino-3-methyl-N-(2-morpholinoethyl)-pentanamide;or a pharmaceutically acceptable salt, solvate, ester, or prodrug thereof.17. A mixture of two or more compounds selected from the group consisting of(2S,3S)-2-amino-3-methyl-N-(2-morpholinoethyl)-pentanamide;(2R,3R)-2-amino-3-methyl-N-(2-morpholinoethyl)-pentanamide;(2R,3S)-2-amino-3-methyl-N-(2-morpholinoethyl)-pentanamide; and(2S,3R)-2-amino-3-methyl-N-(2-morpholinoethyl)-pentanamide;or a pharmaceutically acceptable salt, solvate, ester, or prodrug thereof,with the proviso that when the mixture consists of (2S,3S)-2-amino-3-methyl-N-(2-morpholinoethyl)-pentanamide and (2R,3R)-2-amino-3-methyl-N-(2-morpholinoethyl)-pentanamide, or a pharmaceutically acceptable salt, solvate, ester, or prodrug thereof; then (2S,3S)-2-amino-3-methyl-N-(2-morpholinoethyl)-pentanamide, or a pharmaceutically acceptable salt, solvate, ester, or prodrug thereof, is in an amount not less than about 5% by weight based on the total amount of the mixture.18. A mixture of (2R ,3R)-2-amino-3-methyl-N-(2-morpholinoethyl)-pentanamide and (2S ,3S)-2-amino-3-methyl-N-(2-morpholinoethyl)-pentanamide , or a pharmaceutically acceptable salt , solvate , ester , or prodrug thereof , with the proviso that (2S ,3S)-2-amino-3-methyl-N-(2-morpholinoethyl)-pentanamide , or a pharmaceutically acceptable salt , solvate , ester , or prodrug thereof , is in an amount not less than about 5% by weight based on the total amount ...

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Номер записи: 78
10-04-2014 дата публикации

FUSED HETEROARYL PYRIDYL AND PHENYL BENZENESUFLONAMIDES AS CCR2 MODULATORS FOR THE TREATMENT OF INFLAMMATION

Номер: US20140100237A1
Автор: Krasinski Antoni, Punna Sreenivas, Ungashe Solomon, Wang Qiang, Zeng Yibin
Принадлежит: ChemoCentryx, Inc.

Compounds are provided that act as potent antagonists of the CCR2 receptor. The compounds are generally aryl sulfonamide derivatives and are useful in pharmaceutical compositions, methods for the treatment of CCR2-mediated diseases and as controls in assays for the identification of CCR2 antagonists. 3. The compound or salt of claim 1 , wherein Xis N.4. The compound of or salt thereof claim 3 , wherein Xand Xare N claim 3 , and Xand Xare CR.5. The compound or salt of claim 4 , where Ris Cl.6. The compound or salt of claim 5 , where Ris —CF.7. The compound or salt of claim 6 , where Ris Cl or methyl.8. The compound or salt of claim 7 , where Ris methyl.9. The compound or salt of claim 4 , wherein Ris Cl claim 4 , Ris CF claim 4 , and Ris Cl.12. A composition comprising a pharmaceutically acceptable carrier and a compound or salt of .13. A method of modulating CCR2 function in a cell claim 1 , comprising contacting the cell with a CCR2 modulating amount of the compound or salt of .14. A method of treating a CCR2-mediated condition or disease comprising administering to a subject a therapeutically effective amount of a compound or pharmaceutically acceptable salt of .15. The method of claim 14 , wherein said CCR2-mediated condition or disease is atherosclerosis.16. The method of claim 14 , wherein said CCR2-mediated condition or disease is restenosis.17. The method of claim 14 , wherein said CCR2-mediated condition or disease is multiple sclerosis.18. The method of claim 14 , wherein said CCR2-mediated condition or disease is selected from the group consisting of inflammatory bowel disease claim 14 , renal fibrosis claim 14 , rheumatoid arthritis claim 14 , obesity and noninsulin-dependent diabetes.19. The method of claim 14 , wherein said CCR2-mediated condition or disease is type 2 diabetes.20. The method of claim 14 , wherein said CCR2-mediated condition or disease is selected from the group consisting of chronic obstructive pulmonary disease claim 14 , idiopathic ...

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Номер записи: 79
03-01-2019 дата публикации

Antiviral 4-(2-amino-6-heterocylyl-9h-purin-9-yl)-2-cyclopentene-1 -methanol compounds

Номер: US20190000853A1
Автор: Neil Berry, Paul O&#39;neill
Принадлежит: University of Liverpool

The present invention relates to certain antiviral compounds of formula I as defined herein that function as nucleoside reverse transcriptase inhibitors. The present invention also relates to processes for the preparation of these compounds, pharmaceutical compositions comprising them and to their use for the treatment of retroviral infections, and in particular their use in the treatment of HIV-1 virus.

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Номер записи: 80
06-01-2022 дата публикации

DIHYDROPYRROLOPYRAZOLE DERIVATIVE

Номер: US20220002303A1
Автор: Aga Yasuhiro, Iwase Noriaki, Kimura Tomio, Kono Shigeyuki
Принадлежит:

The present invention provides a compound represented by general formula (I) or a pharmacologically acceptable salt thereof. [In the formula, the two Rs each independently represents a Calkyl group, or are bonded together to form a Calkylene group, A represents a Caryl group (which may be a substituted Caryl group), Z represents a hydrogen atom or a Calkyl group (which may be a substituted Caryl group), or A and Z may be bonded to each other, with the group represented by Z—N-A forming a bicyclic fused heteroaryl group, which may be substituted, and R, R, and Reach independently represents a linear or branched Calkyl group that may be substituted.] 5. A compound selected from the following , or a pharmacologically acceptable salt thereof:3-(1-(tert-butyl) cyclobutane-1-carboxamide)-N-(2-fluorophenyl)-6,6-dimethyl-4,6-dihydropyrrolo [3,4-c] pyrazole-5 (1H)-carboxamide,3-(1-(tert-butyl) cyclobutane-1-carboxamide)-N-(o-tolyl)-6,6-dimethyl-4,6-dihydropyrrolo [3,4-c] pyrazole-5 (1H)-carboxamide,3-(1-(tert-butyl) cyclobutane-1-carboxamide)-N-(2-chloro-6-methylphenyl)-4,6-dihydropyrrolo [3,4-c] pyrazole-5 (1H)-carboxamide,3-(1-(tert-butyl) cyclobutane-1-carboxamide)-N-(5-fluoro-2-methylphenyl)-4,6-dihydropyrrolo [3,4-c] pyrazole-5 (1H)-carboxamide,3-(1-(tert-butyl) cyclobutane-1-carboxamide)-N-(2,5-dimethylphenyl)-4,6-dihydropyrrolo [3,4-c] pyrazole-5 (1H)-carboxamide,3-(1-(tert-butyl) cyclobutane-1-carboxamide)-N-(2,6-dimethylchlorophenyl)-4,6-dihydropyrrolo [3,4-c] pyrazole-5 (1H)-carboxamide,3-(1-(tert-butyl) cyclobutane-1-carboxamide)-N-(2-chloro-6-fluorophenyl)-4,6-dihydropyrrolo [3,4-c] pyrazole-5 (1H)-carboxamide,N-(2-bromo-6-methylphenyl)-3-(1-(tert-butyl) cyclobutane-1-carboxamide)-4,6-dihydropyrrolo [3,4-c] pyrazole-5 (1H)-carboxamide,3-(1-(tert-butyl) cyclobutane-1-carboxamide)-N-(2-fluoro-3,6-dimethylphenyl)-4,6-dihydropyrrolo [3,4-c] pyrazole-5 (1H)-carboxamide,3-(1-(tert-butyl) cyclobutane-1-carboxamide)-N-(6-fluorobenzofuran-7-yl)-4,6-dihydropyrrolo [3,4-c] ...

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Номер записи: 81
02-01-2020 дата публикации

BRK INHIBITORY COMPOUND

Номер: US20200000810A1
Автор: HOTTA Shingo, KURONO Masakuni, YAMAMOTO Shingo, YOSHIDA Atsushi
Принадлежит: ONO PHARMACEUTICAL CO., LTD.

The present invention relates to a Brk inhibitory compound represented by general formula (I) (wherein, all symbols represent the same meanings as the symbols set forth in the specification), a salt thereof, an N-oxide thereof, a solvate thereof, or a prodrug of any of these. 2. The compound according to claim 1 , a salt thereof claim 1 , an N-oxide thereof claim 1 , a solvate thereof claim 1 , or a prodrug of any of these claim 1 , wherein Ris isopropyl claim 1 , tert-butyl claim 1 , isobutyl claim 1 , a C3-6 cycloalkyl claim 1 , or a 3- to 6-membered heterocycloalkyl that may be substituted with a 1-5 halogen or a hydroxyl group.3. The compound according to claim 1 , a salt thereof claim 1 , an N-oxide thereof claim 1 , a solvate thereof claim 1 , or a prodrug of any of these claim 1 , wherein ring 1 is a 9- to 10-membered nitrogen-containing bicyclic aromatic heterocycle.4. The compound according to claim 1 , a salt thereof claim 1 , an N-oxide thereof claim 1 , a solvate thereof claim 1 , or a prodrug of any of these claim 1 , wherein ring 2 is a benzene ring.5. The compound according to claim 1 , a salt thereof claim 1 , an N-oxide thereof claim 1 , a solvate thereof claim 1 , or a prodrug of any of these claim 1 , wherein q is an integer of 1 or more claim 1 , Ris at least one a halogen claim 1 , a C1-3 alkoxy claim 1 , SOR claim 1 , or COR.8. A compound according to the claim 1 , which is:(1) 6-amino-7-(7-fluoro-1H-indazole-4-yl)-2-{[2-fluoro-4-(methylsulfonyl)phenyl]amino}-9-isopropyl-7,9-dihydro-8H-purine-8-one;(2) 6-amino-7-(7-chloro-1H-indazol-4-yl)-2-{[2-fluoro-4-(methylsulfonyl)phenyl]amino}-9-isopropyl-7,9-dihydro-8H-purine-8-one;(3) 6-amino-7-(6,7-difluoro-1H-indazol-4-yl)-2-{[2-fluoro-4-(methylsulfonyl)phenyl]amino}-9-isopropyl-7,9-dihydro-8H-purine-8-one;(4) 6-amino-7-(7-fluoro-1H-indazol-4-yl)-2-{[2-fluoro-4-(methylsulfonyl)phenyl]amino}-9-(2-methyl-2-propanyl)-7,9-dihydro-8H-purine-8-one;(5) 2-[(4-acetyl-2-fluorophenyl)amino]-6-amino-7-(1H-indazol ...

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Номер записи: 82
07-01-2016 дата публикации

FLAGELLAR AND NEEDLE COMPLEX (INJECTOSOME) LOOP AS ANTI BACTERIAL DRUG TARGET

Номер: US20160002239A1
Автор: KITAO Akio, MATSUNAMI Hideyuki, MESHCHERYAKOV Vladimir A, SAMATEY Fadel Alexis
Принадлежит:

The present invention relates to a method for screening a compound that inhibits secretion of toxins into host-cell cytoplasm by virulent bacteria using a needle type III secretion system. The compound of the invention is selected by screening for a compound which interacts with a loop region of the cytoplasmic domain of the membrane protein FlhB from or a paralog thereof. Compositions including the compound of the invention, use of the compound, and methods of treating disorders caused by virulent bacteria are also provided. 1. A method for screening a compound that inhibits secretion of toxins into the host-cell cytoplasm by virulent bacteria using a needle type III secretion system , the method comprising the steps of:{'i': 'Salmonella typhimurium', 'contacting a candidate compound with a C-terminal cytoplasmic domain of the membrane protein FlhB from or a paralog thereof,'}analyzing the interaction of the candidate compound with or around a loop region of FlhB or the paralog threofthereof, andselecting a compound that reduces the flexibility of the loop region or a linker that connects the transmembrane and cytoplasmic domains of FlhB or the paralog thereof, wherein the selected compound is indicated to inhibit the secretion of toxins by virulent bacteria.2Salmonella typhimurium, Aquifex aeolicus, Yersinia pestis, Shigella flexneri, enterohemorrhagic Escherichia coli, Pseudomonas aeruginosa,Vibrio parahaemolyticus.. The method of claim 1 , wherein the virulent bacteria is selected from the group consisting of and3Salmonella typhimuriumEscherichia coli,Yersinia pestis,Salmonella typhimurium,Shigella flexneri.. The method of claim 1 , wherein the paralog of the membrane protein FlhB from is EscU from YscU from SpaS from and Spa40 from4Salmonella. The method of claim 1 , wherein the loop region of the cytoplasmic domain of FlhB or the paralog thereof consists of the amino acid residues ENKMSin numeration.6Salmonella typhimurium. The method of claim 1 , wherein the ...

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Номер записи: 83
07-01-2016 дата публикации

INHIBITORS OF BRUTON'S TYROSINE KINASE

Номер: US20160002241A1
Автор: Chen Wei, FRYE Leah Lynn, Greenwood Jeremy Robert, Loury David J., SHELLEY Mee Yoo, Wang Longcheng, Yan Shunqi
Принадлежит: PHARMACYCLICS, LLC.

Disclosed herein are compounds that form covalent bonds with Bruton's tyrosine kinase (Btk). Also described are irreversible inhibitors of Btk. In addition, reversible inhibitors of Btk are also described. Also disclosed are pharmaceutical compositions that include the compounds. Methods of using the Btk inhibitors are disclosed, alone or in combination with other therapeutic agents, for the treatment of autoimmune diseases or conditions, heteroimmune diseases or conditions, cancer, including lymphoma, and inflammatory diseases or conditions. 3. The compound of claim 2 , wherein Z is C(═O) claim 2 , NHC(═O) claim 2 , N(CH)C(═O) claim 2 , or S(═O).4. The compound of claim 3 , wherein R claim 3 , R claim 3 , and Rare H.5. The compound of claim 3 , wherein Rand Rare H; and Ris L-J-W.6. The compound of claim 5 , wherein Lis a bond claim 5 , substituted or unsubstituted C-Calkylene claim 5 , or substituted or unsubstituted C-Ccycloalkylene; and J is a bond claim 5 , substituted or unsubstituted C-Calkylene claim 5 , substituted or unsubstituted C-Ccycloalkylene claim 5 , substituted or unsubstituted C-Cheteroalkylene claim 5 , substituted or unsubstituted C-Cheterocycloalkylene claim 5 , substituted or unsubstituted C-Carylene claim 5 , or substituted or unsubstituted C-Cheteroarylene.7. The compound of claim 6 , wherein Lis —CH—.8. The compound of claim 6 , wherein J is substituted or unsubstituted C-Calkylene claim 6 , cyclopropyl claim 6 , pyrrolidinyl claim 6 , piperidinyl claim 6 , piperizinyl claim 6 , morpholinyl claim 6 , imidazolyl claim 6 , pyridinyl claim 6 , or phenyl.9. The compound of claim 6 , wherein Lis a bond.10. The compound of claim 5 , wherein J is —CH— and W is NRR.11. The compound of claim 10 , wherein Ris H claim 10 , substituted or unsubstituted C-Calkyl claim 10 , or substituted or unsubstituted C-Ccycloalkyl; and Ris substituted or unsubstituted C-Calkyl claim 10 , substituted or unsubstituted C-Ccycloalkyl claim 10 , substituted or ...

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Номер записи: 84
07-01-2016 дата публикации

IMIDAZOPYRIMIDINE DERIVATIVES

Номер: US20160002242A1
Автор: Busch Michael, Dorsch Dieter, Hoelzemann Guenter, Poeschke Oliver, SEENISAMY Jeyaprakashnarayanan, WEGENER Ansgar
Принадлежит: Merck Patent GmBH

Compounds of the formula I 2. Compounds according to in which{'sup': '2', 'claim-text': {'sup': 3', '3', '1', '3', '3', '3', '3', '3', '1, 'sub': 2', 'p', '2', 'p', '2', 'p', '2', 'p', '2', '2', 'p, 'denotes pyrazolyl, pyrrolidinyl or cyclopentyl, each of which is unsubstituted or monosubstituted by A, [C(R)]Ar, [C(R)]Het, Cyc, [C(R)]OR, CO[C(R)]N(R)or CO[C(R)]Het,'}, 'R'}and pharmaceutically acceptable solvates, salts, tautomers and stereoisomers thereof, including mixtures thereof in all ratios.3. Compounds according to in which [{'sup': 3', '3', '3', '3', '3', '1, 'sub': 2', 'p', '2', 'p', '2', 'p', '2', '2, 'denotes phenyl, which is unsubstituted or mono-, di- or trisubstituted by Hal, A, [C(R)]OR, O[C(R)]OR, [C(R)]Het, CONH, CONA and/or CONA,'}, 'and pharmaceutically acceptable solvates, salts, tautomers and stereoisomers thereof, including mixtures thereof in all ratios., 'Ar'}4. Compounds according to in which 'denotes pyrazolyl, pyridyl, indolyl, isoindolyl, indolinyl, quinolyl or isoquinolyl, each of which is unsubstituted or mono- or disubstituted by A and/or ═O,', 'Het'}and pharmaceutically acceptable solvates, salts, tautomers and stereoisomers thereof, including mixtures thereof in all ratios.5. Compounds according to in which{'sup': '1', 'claim-text': [{'sup': 3', '2, 'sub': 2', 'p, 'denotes pyrazolyl, pyridyl, pyrrolidinyl, piperidinyl, morpholinyl, tetrahydropyranyl or piperazinyl, each of which is unsubstituted or mono- or disubstituted by A and/or [C(R)]Het,'}, 'and pharmaceutically acceptable solvates, salts, tautomers and stereoisomers thereof, including mixtures thereof in all ratios., 'Het'}6. Compounds according to in which {'sub': 3', '2, 'denotes H, CHor NH,'}, 'X'}{'sup': '1', 'claim-text': 'denotes Ar or Het,', 'R'}{'sup': '2', 'claim-text': {'sup': 3', '3', '1', '3', '3', '3', '3', '3', '1, 'sub': 2', 'p', '2', 'p', '2', 'p', '2', 'p', '2', '2', 'p, 'denotes pyrazolyl, pyrrolidinyl or cyclopentyl, each of which is unsubstituted or ...

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Номер записи: 85
07-01-2016 дата публикации

INHIBITORS OF BRUTON'S TYROSINE KINASE

Номер: US20160002243A1
Автор: de Vicente Fidalgo Javier, Dominique Romyr, Lopez-Tapia Francisco Javier, So Sung-Sau
Принадлежит:

This application discloses compounds according to generic Formula (I) wherein all variables are defined as described herein, which inhibit BTK. The compounds disclosed herein are useful to modulate the activity of BTK and treat diseases associated with excessive BTK activity. The compounds are further useful to treat inflammatory and auto immune diseases associated with aberrant B-cell proliferation such as rheumatoid arthritis. Also disclosed are compositions containing compounds of Formula (I) and at least one carrier, diluent or excipient. 2. The compound of claim 1 , wherein Xis —NH.3. The compound of claim 1 , wherein Xis —C(═O).4. The compound of claim 1 , wherein Xis absent.5. The compound of claim 1 , wherein Ais phenyl claim 1 , optionally substituted with one or more A.6. The compound of claim 1 , wherein Xis absent.7. The compound of claim 1 , wherein Ais H.8. The compound of claim 1 , wherein Xis —C(═O).9. The compound of claim 8 , wherein Xis —NH.10. The compound of claim 1 , wherein Xis methylene.11. The compound of claim 1 , wherein Ais phenyl claim 1 , optionally substituted with one or more A.12. The compound of claim 1 , wherein Ais H.13. The compound of claim 1 , wherein Xis absent.14. The compound of claim 1 , wherein Xis —NH claim 1 , Ais pyrazolyl claim 1 , and A is methyl.15. The compound of claim 1 , selected from the group consisting of:4-tert-butyl-N-[3-(7H-purin-6-ylamino)cyclohexyl]benzamide;N-[(3-chlorophenyl)methyl]-3-(9H-purin-6-ylamino)cyclohexane-1-carboxamide;6-N-cyclohexyl-2-N-(1-methylpyrazol-4-yl)-9H-purine-2,6-diamine;6-N-(3-methylcyclohexyl)-2-N-(1-methylpyrazol-4-yl)-9H-purine-2,6-diamine; and4-tert-butyl-N-[3-[[2-[(1-methylpyrazol-4-yl)amino]-9H-purin-6-yl]amino]cyclohexyl]benzamide.16. The compound of claim 1 , selected from the group consisting of:4-tert-Butyl-N-[3-(9H-purin-6-ylamino)-cyclohexyl]-benzamide;3-(9H-Purin-6-ylamino)-cyclohexanecarboxylic acid 3-chloro-benzylamide,N*6*-Cyclohexyl-N*2*-(1-methyl-1H-pyrazol-4-yl ...

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Номер записи: 86
07-01-2016 дата публикации

OXIDATED DERIVATIVES OF TRIAZOLYLPURINES USEFUL AS LIGANDS OF THE ADENOSINE A2A RECEPTOR AND THEIR USE AS MEDICAMENTS

Номер: US20160002244A1
Автор: Cabri Walter, MINETTI Patrizia, PIERSANTI Giovanni, Tarzia Giorgio
Принадлежит:

The present invention relates to new triazolyl purine derivatives of formula (I), processes for their preparation, and to pharmaceutical compositions containing them for the treatment of neurological disorders or cerebral ischaemia for which inhibition of adenosine A2A receptor will result at improving the health state of a patient. 115-. (canceled)17. The compound according to wherein n=2 claim 16 , m=1 and p≧1.18. The compound according to claim 16 , wherein Ris OH or =0 with the meaning of carbonyl.19. The compound according to wherein n=1 and Ris OH or ═O with the meaning of carbonyl.20. The compound according to which is 4-(6-amino-9-methyl-8 [1 claim 16 ,2 claim 16 ,3]triazol-2-yl-9H-purin-2-yl)butan-1-ol claim 16 , 1-(6-amino-9-methyl-8 [1 claim 16 ,2 claim 16 ,3 ]triazol-2-yl-9H-purin-2-yl)butan-1-ol claim 16 , 4-(6-amino-9-methyl-8-[1 claim 16 ,2 claim 16 ,3]triazol-2-yl-9H-purin-2-yl)-butan-2-one claim 16 , 4-(6-amino-9-methyl-8[1 claim 16 ,2 claim 16 ,3]triazol-2-yl-9H-purin-2-yl) butan-2-ol claim 16 , or 1-(6-amino-9-methyl-8-[1 claim 16 ,2 claim 16 ,3]triazol-2-yl-9H-purin-2-yl)-butan-1-one or a pharmaceutically acceptable salt thereof.21. The compound of which is 4-(6-amino-9-methyl-8[1 claim 16 ,2 claim 16 ,3]triazol-2-yl-9H-purin-2-yl) butan-2-one or a pharmaceutically acceptable salt thereof.22. A pharmaceutical composition comprising at least one compound according to or an optically active form claim 16 , or a pharmaceutically acceptable salt thereof and at least one pharmaceutically acceptable vehicle and/or excipient.23. The pharmaceutical composition according to wherein the compound is 4-(6-amino-9-methyl-8[1 claim 22 ,2 claim 22 ,3]triazol-2-yl-9H-purin-2-yl)butan-1-ol claim 22 , 1-(6-amino-9-methyl-8[1 claim 22 ,2 claim 22 ,3]triazol-2-yl-9H-purin-2-yl)butan-1-ol claim 22 , 4-(6-amino-9-methyl-8-[1 claim 22 ,2 claim 22 ,3]triazol-2-yl-9H-purin-2-yl)-butan-2-one claim 22 , 4-(6-amino-9-methyl-8[1 claim 22 ,2 claim 22 ,3]triazol-2-yl-9H-purin- ...

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Номер записи: 87
05-01-2017 дата публикации

A3 ADENOSINE RECEPTOR AGONISTS

Номер: US20170002007A1
Автор: Jacobson Kenneth A., Salvemini Daniela, Tosh Dilip K.
Принадлежит:

Disclosed are compounds of the formula (I) and (II) which are A3 adenosine receptor agonists, pharmaceutical compositions comprising such compounds, and a method of use of these compounds, wherein X, Y, Z, R-R, and R-Rare as defined in the specification. These compounds are selective to the A3 receptor, and are contemplated for use in the treatment or prevention of a number of diseases or conditions, for example, neuropathic pain. 25.-. (canceled)6. The compound or salt of claim 1 , wherein X is NHR claim 1 , Ris C-Calkyl claim 1 , Ris C-Caryl claim 1 , wherein the aryl group is optionally substituted with one or more substituents selected from halo claim 1 , trifluoromethyl claim 1 , hydroxyalkyl claim 1 , alkoxy claim 1 , and any combination thereof claim 1 , or Ris heteroaryl claim 1 , and the heteroaryl group is optionally substituted with one or more substituents selected from halo hydroxy claim 1 , and alkyl.79.-. (canceled)14. The compound or salt of claim 1 , wherein Ris C-Caryl C-Ccycloalkyl claim 1 , wherein the aryl is optionally substituted with C-Calkyl claim 1 , methyl claim 1 , F claim 1 , Cl claim 1 , and Br.16. (canceled)1826.-. (canceled)28. A pharmaceutical composition comprising a compound or salt of and a pharmaceutically acceptable carrier.29. A method for selectively activating an Aadenosine receptor in a mammal or for treating or preventing neuropathic pain in a mammal in need thereof comprising administering to the mammal an effective amount of a compound of or a pharmaceutically acceptable salt thereof.3031.-. (canceled)33. The compound or salt of claim 32 , wherein Ris hydrogen and Y is N.3436.-. (canceled)3841.-. (canceled)43. (canceled)4546.-. (canceled)48. A pharmaceutical composition comprising a compound or salt of and a pharmaceutically acceptable carrier.49. A method for selectively activating an Aadenosine receptor in a mammal or for treating or preventing neuropathic in a mammal in need thereof comprising administering to the ...

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Номер записи: 88
02-01-2020 дата публикации

OXADIAZOLE TRANSIENT RECEPTOR POTENTIAL CHANNEL INHIBITORS

Номер: US20200002340A1
Автор: Beaumier Francis, Chen Huifen, Constantineau-Forget Lea, Dery Martin, GRAND-MAITRE Chantal, Larouche-Gauthier Robin, Lépissier Luce, LU Aijun, SAFINA Brian, Shore Daniel, TERRETT Jack, Villemure Elisia, VOLGRAF Matthew, Ward Stuart
Принадлежит: Genentech, Inc.

The invention relates to compounds of formula I: 9. The compound of wherein the B moiety substituted or unsubstituted fused tricyclic is Ccycloalkyl-Ccycloalkyl-Caryl.10. The compound of wherein B is substituted or unsubstituted Ccycloalkyl-Ccycloalkyl-Caryl.14. The compound of wherein the B moiety is fused (Ccycloalkyl)-(4-6 membered heterocycloalkyl) or bridged 6- or 7-membered cycloalkyl or heterocycloalkyl.22. A pharmaceutical composition claim 1 , comprising a compound as described in or a pharmaceutically acceptable salt thereof claim 1 , and a pharmaceutically acceptable carrier claim 1 , diluent or excipient.23. A method for treating a respiratory disorder in a mammal comprising claim 1 , administering a compound as described in or a pharmaceutically acceptable salt thereof to the mammal. This application is a continuation of International Application No. PCT/EP2018/055690 filed on Mar. 7, 2018, which claims the priority of International Application Nos. PCT/CN2017/075843 filed on Mar. 7, 2017 and PCT/CN2018/074543 filed on Jan. 30, 2018, the disclosures of which are incorporated herein by reference.The present invention relates to oxadiazole compounds, their manufacture, pharmaceutical compositions containing them and their use as Transient Receptor Potential (TRP) cation channel antagonists.TRP channels are a class of ion channels found on the plasma membrane of a variety of human (and other animal) cell types. There are at least 28 known human TRP channels which are broken into a number of families or groups based upon sequence homology and function. Transient receptor potential cation channel, subfamily A, member 1 (TRPA1) is a non-selective cation conducting channel that modulates membrane potential via flux of sodium, potassium and calcium. TRPA1 has been shown to be highly expressed in the human dorsal root ganglion neurons and peripheral sensory nerves. In humans, TRPA1 is activated by a number of reactive compounds such as acrolein, ...

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Номер записи: 89
04-01-2018 дата публикации

2-(HET)ARYL-SUBSTITUTED FUSED BICYCLIC HETEROCYCLE DERIVATIVES AS PESTICIDES

Номер: US20180002345A1
Автор: EILMUS SASCHA, FISCHER Ruediger, Goergens Ulrich, ILG Kerstin, Portz Daniela, Turberg Andreas, WILCKE DAVID
Принадлежит:

The invention relates to novel compounds of the formula (I) 2. Compound of formula (I) according to wherein{'sup': 1', '+', '−', '4, 'Arepresents nitrogen, ═N—O or ═C—R,'}{'sup': 2', '5, 'Arepresents —N—R, oxygen or sulphur,'}{'sup': '3', 'Arepresents oxygen,'}{'sup': 4', '+', '−', '4, 'Arepresents nitrogen, ═N—O or ═C—R,'}{'sup': '1', 'sub': 1', '4', '1', '4', '1', '4', '1', '4', '1', '4', '1', '4', '1', '4', '1', '4', '2', '4', '2', '4', '1', '4', '2', '4', '1', '4', '2', '4', '2', '4', '2', '4', '2', '4', '1', '4', '2', '4', '1', '4', '2', '4', '2', '4', '3', '6', '3', '6', '3', '6', '1', '4', '3', '6', '3', '6', '1', '4', '1', '4', '3', '6', '1', '4', '1', '4', '1', '4', '1', '4', '1', '4', '1', '4', '1', '4', '1', '4', '1', '4', '1', '4', '1', '4', '1', '4', '1', '4', '1', '4', '1', '4', '1', '4, 'Rrepresents (C-C)-alkyl, (C-C)-hydroxyalkyl, (C-C)-haloalkyl, (C-C)-cyanoalkyl, (C-C)-alkoxy-(C-C)-alkyl, (C-C)-haloalkoxy-(C-C)-alkyl, (C-C)-alkenyl, (C-C)-alkenyloxy-(C-C)-alkyl, (C-C)-haloalkenyloxy-(C-C)-alkyl, (C-C)-haloalkenyl, (C-C)-cyanoalkenyl, (C-C)-alkynyl, (C-C)-alkynyloxy-(C-C)-alkyl, (C-C)-haloalkynyloxy-(C-C)-alkyl, (C-C)-haloalkynyl, (C-C)-cyanoalkynyl, (C-C)-cycloalkyl, (C-C)-cycloalkyl-(C-C)-cycloalkyl, (C-C)-alkyl-(C-C)-cycloalkyl, halo-(C-C)-cycloalkyl, (C-C)-alkylamino, di-(C-C)-alkylamino, (C-C)-cycloalkylamino, (C-C)-alkylcarbonylamino, (C-C)-alkylthio-(C-C)-alkyl, (C-C)-haloalkylthio-(C-C)-alkyl, (C-C)-alkylsulphinyl-(C-C)-alkyl, (C-C)-haloalkylsulphinyl-(C-C)-alkyl, (C-C)-alkylsulphonyl-(C-C)-alkyl, (C-C)-alkylcarbonyl-(C-C)-alkyl, (C-C)-haloalkylcarbonyl-(C-C)-alkyl, (C-C)-alkylsulphonylamino,'}{'sub': 1', '4', '1', '4', '2', '4', '2', '4', '3', '6', '1', '4', '3', '4', '1', '4', '1', '4', '1', '4', '1', '4', '1', '4', '1', '4', '1', '4, 'or represents (C-C)-alkyl, (C-C)-alkoxy, (C-C)-alkenyl, (C-C)-alkynyl, (C-C)cycloalkyl, each of which is optionally mono- or disubstituted by identical or different substituents from the group consisting of ...

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Номер записи: 90
07-01-2021 дата публикации

RIP1 INHIBITORY COMPOUNDS AND METHODS FOR MAKING AND USING THE SAME

Номер: US20210002236A1
Автор: Bhamidipati Somasekhar, Masuda Esteban, Shaw Simon, Taylor Vanessa
Принадлежит: Rigel Pharmaceuticals, Inc.

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. 2. The compound of claim 1 , wherein the compound is in the form of a pharmaceutically acceptable salt.3. A pharmaceutical composition claim 1 , comprising:{'claim-ref': {'@idref': 'CLM-00001', 'claim 1'}, 'the compound according to ; and'}an excipient.4. The pharmaceutical composition of claim 3 , further comprising a therapeutic agent selected from an aminosalicylate claim 3 , nambumetone claim 3 , naproxen claim 3 , oxaprozin claim 3 , piroxicam claim 3 , salsalate claim 3 , sulindac claim 3 , tolmetin claim 3 , mercaptopurine claim 3 , dexamethasone claim 3 , hydrocortisone claim 3 , prednisone claim 3 , methylprednisolone and prednisolone claim 3 , antilymphocyte globulin claim 3 , antithymocyte globulin claim 3 , azacytidine claim 3 , decitabine claim 3 , mechlorothamine claim 3 , cyclophosphamide claim 3 , ifosfamide claim 3 , melphalan claim 3 , chlorambucil claim 3 , busulfan claim 3 , carmustine claim 3 , methotrexate claim 3 , fluorouracil claim 3 , cytosine arbinoside claim 3 , thioguanine claim 3 , azathioprine claim 3 , vinblastine claim 3 , vincristine claim 3 , paclitaxel claim 3 , colchicine claim 3 , actinomycin D claim 3 , daunorubicin claim 3 , bleomycin claim 3 , L-asparaginase claim 3 , cisplatin claim 3 , carboplatin claim 3 , prednisone claim 3 , dexamethasone claim 3 , amino glutethimide claim 3 , formestane claim 3 , anastrozole claim 3 , hydroxyprogesterone caproate claim 3 , medroxyprogesterone claim 3 , tamoxifen claim 3 , ipilimumab claim 3 , nivolumab claim 3 , lambrolizumab claim 3 , pembrolizumab claim 3 , elotuzumab ...

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Номер записи: 91
07-01-2021 дата публикации

RIP1 INHIBITORY COMPOUNDS AND METHODS FOR MAKING AND USING THE SAME

Номер: US20210002237A1
Автор: Bhamidipati Somasekhar, Masuda Esteban, Shaw Simon, Taylor Vanessa
Принадлежит: Rigel Pharmaceuticals, Inc.

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. 2. The compound of claim 1 , wherein the compound is in the form of a pharmaceutically acceptable salt.3. A pharmaceutical composition claim 1 , comprising:{'claim-ref': {'@idref': 'CLM-00001', 'claim 1'}, 'the compound according to ; and'}an excipient.4. The pharmaceutical composition of claim 3 , further comprising a therapeutic agent selected from an aminosalicylate claim 3 , nambumetone claim 3 , naproxen claim 3 , oxaprozin claim 3 , piroxicam claim 3 , salsalate claim 3 , sulindac claim 3 , tolmetin claim 3 , mercaptopurine claim 3 , dexamethasone claim 3 , hydrocortisone claim 3 , prednisone claim 3 , methylprednisolone and prednisolone claim 3 , antilymphocyte globulin claim 3 , antithymocyte globulin claim 3 , azacytidine claim 3 , decitabine claim 3 , mechlorothamine claim 3 , cyclophosphamide claim 3 , ifosfamide claim 3 , melphalan claim 3 , chlorambucil claim 3 , busulfan claim 3 , carmustine claim 3 , methotrexate claim 3 , fluorouracil claim 3 , cytosine arbinoside claim 3 , thioguanine claim 3 , azathioprine claim 3 , vinblastine claim 3 , vincristine claim 3 , paclitaxel claim 3 , colchicine claim 3 , actinomycin D claim 3 , daunorubicin claim 3 , bleomycin claim 3 , L-asparaginase claim 3 , cisplatin claim 3 , carboplatin claim 3 , prednisone claim 3 , dexamethasone claim 3 , amino glutethimide claim 3 , formestane claim 3 , anastrozole claim 3 , hydroxyprogesterone caproate claim 3 , medroxyprogesterone claim 3 , tamoxifen claim 3 , ipilimumab claim 3 , nivolumab claim 3 , lambrolizumab claim 3 , pembrolizumab claim 3 , elotuzumab ...

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Номер записи: 92
07-01-2021 дата публикации

BICYCLIC HETEROCYCLIC DERIVATIVES

Номер: US20210002278A1
Автор: Buchstaller Hans-Peter
Принадлежит: Merck Patent GmBH

Compounds of the formula Ia or of the formula Ib 2. A compound according to claim 1 , in whichAr denotes phenyl, which is unsubstituted or mono-, di-, tri-, tetra- or pentasubstituted by Hal, A, CN and/or OA,or a pharmaceutically acceptable salt, tautomer, stereoisomer, or mixture thereof in all ratios.3. A compound according to claim 1 , in whichHet denotes pyrimidyl, pyridyl, pyridazinyl, pyrazinyl, piperidinyl, pyrrolidinyl, pyrazolyl, thiazolyl, imidazolyl, furanyl, thiophenyl, pyrrolyl, oxazolyl, isoxazolyl, triazolyl, oxadiazolyl or thiadiazolyl, each of which is unsubstituted or mono- or disubstituted by Hal, A and/or OA,or a pharmaceutically acceptable salt, tautomer, stereoisomer, or mixture thereof in all ratios.4. A compound according to in whichX denotes CH or N,Y denotes CH or N,{'sup': '1', 'sub': 2', 'n', '2', 'n, 'Rdenotes H, A, (CH)Ar, (CH)Het or Cyc,'}{'sup': '2', 'sub': '3', 'Rdenotes H or CH,'}Ar denotes phenyl, which is unsubstituted or mono-, di-, tri-, tetra- or pentasubstituted by Hal, A, CN and/or OA,Het denotes pyrimidyl, pyridyl, pyridazinyl, pyrazinyl, piperidinyl, pyrrolidinyl, pyrazolyl, thiazolyl, imidazolyl, furanyl, thiophenyl, pyrrolyl, oxazolyl, isoxazolyl, triazolyl, oxadiazolyl or thiadiazolyl, each of which is unsubstituted or mono- or disubstituted by Hal, A and/or OA,Cyc denotes cyclic alkyl with 3, 4, 5, 6 or 7 C-atoms, which is unsubstituted or monosubstituted by OH,{'sub': '2', 'sup': '4', 'A denotes unbranched or branched alkyl with 1-10 C-atoms, wherein one or two non-adjacent CH- and/or CH-groups may in each case be replaced by N-, O- or S-atoms and/or wherein 1-7 H-atoms may each be replaced by R,'}{'sup': '4', 'Rdenotes F, Cl or OH,'}Hal denotes F, Cl, Br or I,n denotes 0, 1 or 2,or a pharmaceutically acceptable salt, tautomer, stereoisomer, or mixture thereof in all ratios.5. (canceled)7. A pharmaceutical composition comprising at least one compound according to claim 1 , and optionally a pharmaceutically acceptable ...

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Номер записи: 93
13-01-2022 дата публикации

sGC STIMULATORS

Номер: US20220009937A1
Автор: Iyengar Rajesh R., Jung Joon, Lee Thomas Wai-Ho, Renhowe Paul Allan, Rennie Glen Robert, Tang Kim
Принадлежит:

The present disclosure relates to stimulators of soluble guanylate cyclase (sGC), pharmaceutical formulations comprising them and their uses thereof, alone or in combination with one or more additional agents, for treating various diseases, wherein an increase in the concentration of nitric oxide (NO) or an increase in the concentration of cyclic Guanosine Monophosphate (cGMP), or both, or an upregulation of the NO pathway is desirable. The compounds are of Formula I: 3. A compound according to claim 2 , or a pharmaceutically acceptable salt thereof claim 2 , wherein ring B is phenyl.4. A compound according to claim 2 , or a pharmaceutically acceptable salt thereof claim 2 , wherein each Jis independently selected from halogen claim 2 , a Calkyl claim 2 , —ORand —OR.5. A compound according to claim 4 , or a pharmaceutically acceptable salt thereof claim 4 , wherein n is 2 and each Jis a halogen atom.7. A compound according to claim 6 , or a pharmaceutically acceptable salt thereof claim 6 , wherein Jis a Calkyl chain claim 6 , optionally substituted by up to 5 instances of fluorine.8. A compound according to claim 6 , or a pharmaceutically acceptable salt thereof claim 6 , wherein Ris H or Calkyl optionally and independently substituted with 0-5 occurrences of R; and Ris halo in each instance.9. A compound according to claim 6 , wherein Ris —CF.10. A compound according to claim 7 , or a pharmaceutically acceptable salt thereof claim 7 , wherein q is 0.11. A compound according to claim 7 , or a pharmaceutically acceptable salt thereof claim 7 , wherein each instance of Jis hydrogen.13. A compound according to claim 12 , or a pharmaceutically acceptable salt thereof claim 12 , wherein Ris H or Calkyl optionally and independently substituted with 0-5 occurrences of R; and Ris halo in each instance.14. A compound according to claim 12 , wherein Ris —CF.15. A compound according to claim 12 , or a pharmaceutically acceptable salt thereof claim 12 , wherein q is 0.16. A ...

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Номер записи: 94
20-01-2022 дата публикации

SIX-MEMBERED AND SIX-MEMBERED HETEROCYCLIC COMPOUND AND USES THEREOF SERVING AS PROTEIN RECEPTOR KINASE INHIBITOR

Номер: US20220017512A1
Автор: Feng Zhiyong, JIANG Lei, JIN Xian, QIAO Zhi, Shang Ke, SHOU Jianyong, WU Danyi, XU Lingling, Xu Yuan, ZHANG Shuyun, Zhang Yi, Zhang Yuxing
Принадлежит:

Provided are a preparation and applications of a six-membered fused with six-membered heterocyclic compound, specifically, provided in the present invention is a compound as represented by formula I as follows, where the definitions of the groups are as described in the description. The compound has TRK kinase inhibiting activity and can serve as a pharmaceutical composition for treating TRK dysfunction-related diseases. 10. A pharmaceutical composition claim 1 , wherein the pharmaceutical composition comprises (1) the compound of claim 1 , or a stereoisomer thereof claim 1 , tautomer thereof claim 1 , or a pharmaceutically acceptable salt claim 1 , hydrate or solvate thereof claim 1 , and (2) pharmaceutically acceptable carriers.11. The use of claim 10 , wherein the disease is selected from the group consisting of cancer claim 10 , proliferative disease claim 10 , pain claim 10 , skin disease or condition claim 10 , metabolic disease claim 10 , muscle disease claim 10 , neurological disease claim 10 , autoimmune disease claim 10 , itching caused by dermatitis claim 10 , inflammation related diseases claim 10 , bone related diseases.12. Use of the compound of claim 10 , or a stereoisomer or a tautomer thereof claim 10 , or a pharmaceutically acceptable salt claim 10 , hydrate or solvate thereof claim 10 , or the pharmaceutical composition of claim 10 , in the preparation of a pharmaceutical composition for preventing and/or treating diseases related to TRK function abnormalities (abnormal activation functions induced by TRK gene amplification claim 10 , overexpression claim 10 , mutation or gene fusion).13. The use of claim 12 , wherein the disease is selected from the group consisting of cancer claim 12 , proliferative disease claim 12 , pain claim 12 , skin disease or condition claim 12 , metabolic disease claim 12 , muscle disease claim 12 , neurological disease claim 12 , autoimmune disease claim 12 , itching caused by dermatitis.14. A TRK kinase inhibitor claim ...

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Номер записи: 95
11-01-2018 дата публикации

NATURAL KILLER CELLS AND USES THEREOF

Номер: US20180008637A1
Автор: KANG Lin, Murphy Brian, NORDBERG Andrea, VOSKINARIAN-BERSE Vanessa, Wilson Keith
Принадлежит: Anthrogenesis Corporation

Provided herein are methods of producing natural killer (NK) cells using a three-stage expansion and differentiation method with media comprising stem cell mobilizing factors. Also provided herein are methods of suppressing tumor cell proliferation using the NK cells and the NK cell populations produced by the three-stage methods described herein, as well as methods of treating individuals having cancer or a viral infection, comprising administering the NK ce3lls and the NK cell populations produced by the three-stage methods described herein to an individual having the cancer or viral infection. 1. A method of producing a cell population comprising natural killer cells , comprising the steps of:(a) culturing hematopoietic stem or progenitor cells in a first medium comprising a stem cell mobilizing agent and thrombopoietin (Tpo) to produce a first population of cells;(b) culturing the first population of cells in a second medium comprising a stem cell mobilizing agent and interleukin-15 (IL-15), and lacking Tpo, to produce a second population of cells; and(c) culturing the second population of cells in a third medium comprising IL-2 and IL-15, and lacking a stem cell mobilizing agent and LMWH, to produce a third population of cells;wherein the third population of cells comprises natural killer cells that are CD56+, CD3−, CD16− or CD16+, and CD94+ or CD94−, and wherein at least 80% of the natural killer cells are viable.2. The method of claim 1 , wherein said hematopoietic stem cells are CD34+ hematopoietic stem cells.3. The method of claim 1 , wherein said hematopoietic stem cells are placental hematopoietic stem cells.4. The method of claim 3 , wherein said placental hematopoietic stem cells are obtained from claim 3 , or obtainable from claim 3 , human placental perfusate.5. The method of claim 3 , wherein said placental hematopoietic stem cells are obtained from claim 3 , or obtainable from claim 3 , nucleated cells isolated from human placental perfusate.6. The ...

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Номер записи: 96
09-01-2020 дата публикации

Therapeutic applications of malt1 inhibitors

Номер: US20200009135A1
Автор: Fredrik ÖBERG, Mark ALBERTELLA
Принадлежит: Medivir AB

The present invention relates to novel applications for inhibitors, notably small molecule inhibitors, of the protease in which the inhibitors are used in an immunooncology setting to treat certain cancers. This in turn means that the compounds are directed to immune components and not to the tumour tissue directly.

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Номер записи: 97
27-01-2022 дата публикации

Deuterium-Substituted 7-Substituted-2-(Benzylamino)-6-Ozopurine Compounds and Uses Thereof

Номер: US20220024925A1
Автор: Yu Xiang Y.
Принадлежит:

The invention relates to compounds of formula (I): The compounds are useful as antibacterial agents, especially again -associated diseases. 2. The compound of claim 1 , wherein at least one of Y claim 1 , Y claim 1 , Y claim 1 , and Yis deuterium.4. The compound of claim 2 , wherein the level of deuterium incorporation at each of Y claim 2 , Y claim 2 , Y claim 2 , and Ydesignated as deuterium is at least 52.5% claim 2 , at least 75% claim 2 , at least 82.5% claim 2 , at least 90% claim 2 , at least 95% claim 2 , at least 97% claim 2 , at least 98% claim 2 , or at least 99%.5. The compound of claim 1 , wherein at least one of least one of Y claim 1 , Y claim 1 , Y claim 1 , Y claim 1 , Yand Yis deuterium.7. The compound of claim 5 , wherein the level of deuterium incorporation at each of Y Y claim 5 , Y claim 5 , Y claim 5 , Y claim 5 , Yand Ydesignated as deuterium is at least 52.5% claim 5 , at least 75% claim 5 , at least 82.5% claim 5 , at least 90% claim 5 , at least 95% claim 5 , at least 97% claim 5 , at least 98% claim 5 , or at least 99%.8. The compound of claim 1 , wherein at least one of Y claim 1 , Y claim 1 , Y claim 1 , Y claim 1 , Y claim 1 , Y claim 1 , Y claim 1 , Y claim 1 , Y claim 1 , Y claim 1 , Y claim 1 , Y claim 1 , Y claim 1 , Y claim 1 , Y claim 1 , Y claim 1 , Yand Yis deuterium.10. The compound of claim 8 , wherein the level of deuterium incorporation at each of Y claim 8 , Y claim 8 , Y claim 8 , Y claim 8 , Y claim 8 , Y claim 8 , Y claim 8 , Y claim 8 , Y claim 8 , Y claim 8 , Y claim 8 , Y claim 8 , Y claim 8 , Y claim 8 , Y claim 8 , Y claim 8 , Yand Ydesignated as deuterium is at least 52.5% claim 8 , at least 75% claim 8 , at least 82.5% claim 8 , at least 90% claim 8 , at least 95% claim 8 , at least 97% claim 8 , at least 98% claim 8 , or at least 99%.12. A pharmaceutical composition comprising a compound of claim 1 , and a pharmaceutically acceptable excipient.13Clostridium difficileClostridium difficile. A method of inhibiting ...

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Номер записи: 98
11-01-2018 дата публикации

SMALL MOLECULES FOR THE TREATMENT OF PRIMARY CANCER AND CANCER METASTASIS

Номер: US20180009809A1
Автор: Jiang Jean X.
Принадлежит: The Board of Regents of the University of Texas System

Certain embodiments are directed to non-hydrolysable ATP analogs and adenosine receptor antagonists that inhibit migration and growth of cancer cells. 2. The compound of claim 1 , wherein R1 is selected from hydrogen claim 1 , cyano claim 1 , C1 to C3 alkyl claim 1 , halo claim 1 , or heteromethyl claim 1 , and R2 is a hydrogen or halogen.3. The compound of claim 2 , wherein R1 is a hydrogen claim 2 , fluoro claim 2 , methyl claim 2 , cyano claim 2 , or trifluoromethyl.4. The compound of claim 1 , wherein R1 is cyano and R2 is hydrogen claim 1 , R1 is hydrogen and R2 is hydrogen claim 1 , R1 is trifluoromethyl and R2 is hydrogen claim 1 , R1 methyl and R2 is hydrogen claim 1 , and R1 is fluoro and R2 is fluoro.5. A method for treating a cancer patient comprising administering to the patient an effective amount of a one or more compounds of .6. The method of claim 5 , wherein the cancer is breast cancer.7. The method of claim 5 , wherein one or more compounds of are administered intravenously.8. The method of claim 5 , wherein one or more compounds of are administered orally.10. The compound of claim 9 , wherein R3 is difluoro methyl claim 9 , cyclopropyl claim 9 , cyclobutyl claim 9 , or β-tetrahydrofuran.11. A method for treating a cancer patient comprising administering to the patient an effective amount of one or more compounds of . This application claims priority to U.S. Provisional Application Ser. No. 62/104,705 filed Jan. 17, 2015, which is incorporated herein by reference in its entirety.The bone is the most common site of metastasis in patients with advanced cancers including breast and prostate cancers (Jin et al. (2011) 128, 2545-2561; Kohno, (2008) 13, 18-23). Bone metastases are major, potentially fatal complications in patients with advanced cancers. Almost all patients with skeletal metastases have significantly decreased quality of life due to intense pain, pathological fractures, spinal cord compression, and metabolic complications (Welch et al. ( ...

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Номер записи: 99
11-01-2018 дата публикации

HIV INHIBITING BICYCLIC PYRIMIDINE DERIVATIVES

Номер: US20180009819A1
Автор: DELEST Bruno Francois Marie, Guillemont Jérôme Emile Georges, Heeres Jan, Janssen Paul Adriaan Jan, Lewi Paulus Joannes, PAUGAM Mikaël
Принадлежит:

HIV replication inhibitors of formula 121-. (canceled)23. A compound according to claim 22 , wherein{'sup': 1', '2', '3', '4, '-a=a-a≦a- represents a bivalent radical of formula —CH═CH—CH═CH— (a-1);'}{'sup': 1', '2', '3', '4, '-b=b-b=b- represents a bivalent radical of formula —CH═CH—CH═CH— (b-1);'}n is 0, 1 or 2;m is 0, 1 or 2; and{'sup': '1', 'sub': 1-6', '1-6', '1-6, 'Ris a member selected from the group consisting of: hydrogen; formyl; Calkylcarbonyl; Calkyl; and Calkyloxycarbonyl.'}26. A compound according to claim 22 , wherein{'sup': 2', '6', '6', '6, 'sub': 1-6', '2-6', '2-6', '1-6', '1-6, 'Ris a member selected from the group consisting of: hydroxy; halo; Calkyl optionally substituted with one substituent selected from halo, cyano and —C(═O)R; Calkenyl optionally substituted with one substituent selected from halo, cyano or —C(═O)R; Calkynyl optionally substituted with one substituent selected from halo, cyano or —C(═O)R; Calkyloxycarbonyl; carboxyl; cyano; nitro; amino; mono- or di(Calkyl)-amino; and trifluoromethyl;'}{'sup': 2a', '13', '13', '14', '13', '13', '14', '15', '16', '9', '10', '9', '10', '9', '10', '9', '10', '9', '10, 'sub': 1-6', '1-6', '1-6', '1-6', '1-6', '1-6', '1-6', '1-6', '1-6', '1-6', '1-6', '2-6', '1-6', '2-6', '1-6, 'Ris a member selected from the group consisting of: cyano; aminocarbonyl; amino; Calkyl; halo; Calkyloxy wherein the Calkyl moiety of the Calkyloxy may optionally be substituted with cyano; NHR; NRR; —C(═O)—NHR; —C(═O)—NRR; —C(═O)—R; —CH═N-NH—C(═O)—R; Calkyl substituted with one substituent selected from halo, cyano, —C(═O)—NRR, and —C(═O)—Calkyl; Calkyl substituted with hydroxy and a second substituent selected from halo, cyano, —C(═O)—NRR, and —C(═O)—Calkyl; CalkyloxyCalkyl optionally substituted with one substituent selected from halo, cyano, —C(═O)—NRR, and —C(═O)—Calkyl; Calkenyl substituted with one substituent selected from halo, cyano, —C(═O)—NRR, and —C(═O)—Calkyl; and Calkynyl substituted with one substituent ...

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Номер записи: 100