Настройки

Укажите год
-

Небесная энциклопедия

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

Подробнее
-

Мониторинг СМИ

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

Подробнее

Форма поиска

Поддерживает ввод нескольких поисковых фраз (по одной на строку). При поиске обеспечивает поддержку морфологии русского и английского языка
Ведите корректный номера.
Ведите корректный номера.
Ведите корректный номера.
Ведите корректный номера.
Укажите год
Укажите год
Применить Всего найдено 11559. Отображено 100.
16-02-2012 дата публикации

Design, synthesis and evaluation of procaspase activating compounds as personalized anti-cancer drugs

Номер: US20120040995A1
Автор: Chris J. Novotny, Danny Chung Hsu, Diana C. West, Paul J. Hergenrother, Quinn Patrick Peterson, Timothy M. Fan
Принадлежит: University of Illinois

Compositions and methods are disclosed in embodiments relating to induction of cell death such as in cancer cells. Compounds and related methods for synthesis and use thereof, including the use of compounds in therapy for the treatment of cancer and selective induction of apoptosis in cells are disclosed. Compounds are disclosed that have lower neurotoxicity effects than other compounds.

Подробнее
Номер записи: 1
16-02-2012 дата публикации

Substituted acylguanidine derivatives (as amended)

Номер: US20120041036A1
Автор: Isao Kinoyama, Takehiro Miyazaki, Takuya Washio, Yohei Koganemaru
Принадлежит: Astellas Pharma Inc

An object of the present invention is to provide an excellent agent for treating or preventing dementia, schizophrenia based on serotonin 5-HT 5A receptor modulating action. It was discovered that acylguanidine derivatives, in which the guanidine is bonded to one ring of a naphthalene via a carbonyl group and a cyclic group is bonded to the other ring thereof, exhibit potent the 5-HT 5A receptor modulating action and excellent pharmacological actions based on the action. The present invention is useful as an excellent agent for treating or preventing dementia, schizophrenia, bipolar disorder or attention deficit hyperactivity disorder.

Подробнее
Номер записи: 2
22-03-2012 дата публикации

Metallo-beta-lactamase inhibitors

Номер: US20120071457A1
Автор: Akihiro Morinaka, Ken Chikauchi, Mizuyo Ida, Takao Abe, Toshiaki Kudo, Yukiko Hiraiwa
Принадлежит: Individual

A new metallo-β-lactamase inhibitor which acts as a medicament for inhibiting the inactivation of β-lactam antibiotics and recovering anti-bacterial activities is disclosed. The maleic acid derivatives having the general formula (I) have metallo-β-lactamase inhibiting activities. It is possible to recover the anti-bacterial activities of β-lactam antibiotics against metallo-β-lactamase producing bacteria by combining the compound of the general formula (I) with β-lactam antibiotics.

Подробнее
Номер записи: 3
05-04-2012 дата публикации

Novel Compounds, Pharmaceutical Compositions Containing Same, Methods of Use for Same, and Methods for Preparing Same

Номер: US20120083471A1
Автор: Craig A. Townsend, Edward Wydysh, Francis Kuhajda, Gabriele Valeria Ronnett
Принадлежит: JOHNS HOPKINS UNIVERSITY

The present invention relates to novel pharmaceutical compositions containing the same, and methods of use for a variety of therapeutically valuable uses including, but not limited to, treating obesity by inhibiting the activity of Glycerol 3-phosphate acyltransferase (GPAT).

Подробнее
Номер записи: 4
10-05-2012 дата публикации

Compound inhibiting in vivo phosphorus transport and medicine containing the same

Номер: US20120115851A1
Автор: Nobuaki Eto, Rika Nagao, Tetsuko Kazama
Принадлежит: Kyowa Hakko Kirin Co Ltd

An objective of the present invention is to provide compounds that can effectively suppress the concentration of phosphorus in serum to effectively prevent or treat diseases induced by an increase in concentration of phosphate in serum. The compounds according to the present invention are compounds represented by formula (I) and pharmaceutically acceptable salts and solvates thereof: wherein A represents an optionally substituted five- to nine-membered unsaturated carbocyclic moiety or a five- to nine-membered unsaturated heterocyclic moiety, and represents a single bond or a double bond, R 5 represents optionally substituted aryl or the like, Z represents —N═CHR 6 R 7 or the like, R 6 and R 7 represent H, optionally substituted alkyl, optionally substituted aryl or the like, R 101 and R 102 together form ═O, and R 103 and R 104 represent H, or R 101 and R 104 together from a bond, and R 102 and R 103 together form a bond.

Подробнее
Номер записи: 5
17-05-2012 дата публикации

Compounds and compositions comprising cdk inhibitors and methods for treating cancer

Номер: US20120121692A1
Автор: Binghe Wang, Hao Fang, Wen Fang Xu, Yan Ling Li
Принадлежит: Georgia State University Research Foundation Inc, Shandong University

Disclosed herein are compounds suitable for use as antitumor agents, methods for treating cancer wherein the disclosed compounds are used in making a medicament for the treatment of cancer, methods for treating a tumor comprising, administering to a subject a composition comprising one or more of the disclosed cytotoxic agents, and methods for preparing the disclosed antitumor agents.

Подробнее
Номер записи: 6
17-05-2012 дата публикации

Substituted carbamoylcycloalkyl acetic acid derivatives as nep

Номер: US20120122764A1
Автор: Gary Michael Ksander, Muneto Mogi, Nikolaus Schiering, Qian Liu, Rajeshri Ganesh Karki, Robert Sun, Toshio Kawanami
Принадлежит: NOVARTIS AG

The present invention provides a compound of formula I; or a pharmaceutically acceptable salt thereof, wherein R 1 , R 2 , R 3 , R 4 , R 5 , B, X, m and n are defined herein. The invention also relates to a method for manufacturing the compounds of the invention, and its therapeutic uses. The present invention further provides pharmaceutical composition of compounds of the invention, and a combination of pharmacologically active agents and a compound of the invention.

Подробнее
Номер записи: 7
14-06-2012 дата публикации

Enzyme inhibitors

Номер: US20120149736A1
Автор: Alastair David Graham Donald, Andrew James Belfield, Carl Leslie North, David Festus Charles Moffat, Stewart Andrew Wayne Jones
Принадлежит: Chroma Therapeutics Ltd

Compounds of formula (I), inhibit HDAC activity: wherein A, B and D independently represent ═CH— or ═N—; W is —CH═CH— Or —CH 2 CH 2 —; R 1 is a carboxylic acid group (—COOH), or an ester group which is hydrolysable by one or more intra-cellular carboxylesterase enzymes to a carboxylic acid group; R2 and R3 are selected from the side chains of a natural or non-nat-ural alpha amino acid, provided that neither R2 nor R3 is hydrogen, or R2 and R3, taken together with the carbon to which they are attached, form a 3-6 membered saturated cycloalkyl or heterocyclyl ring; Y is a bond, —C(═O)—, —S(═O)2—, —C(═O)O—, —C(═O)NR′—, —C(═5)—NR′, —C(═NH)NR′ or —S(═O) 2 NR — wherein R′ is hydrogen or optionally substituted C 1 —C 6 alkyl; L 1 is a divalent radical of formula —(Alk 1 ) m ,(Q) n (Alk 2 ) p — wherein m, n, p, Q, Alk 1 and Alk 2 are as defined in the claims; X 1 represents a bond; —C(═O); or —S(═O) 2 —; —NR 4 C(═O)—, —C(═O)NR 4 —,— NR 4 C(═O)NR 5 —, —NR 4 S(═O) 2 —, or —S(═O) 2 NR 4 — wherein R4 and R5 are independently hydrogen or optionally substituted C 1 -C 6 alkyl; and z is 0 or 1.

Подробнее
Номер записи: 8
21-06-2012 дата публикации

Phosphorous derivatives as chemokine receptor modulators

Номер: US20120157413A1
Автор: Haiqing Yuan, John E. Donello, Michael E. Garst, Richard I. Beard, Veena Viswanath, Xiaoxia Liu
Принадлежит: Allergan Inc

The present invention relates to novel phosphorous derivatives, processes for preparing them, pharmaceutical compositions containing them and their use as pharmaceuticals as modulators of chemokine receptors.

Подробнее
Номер записи: 9
02-08-2012 дата публикации

Electrochromic compound, electrochromic composition, and display element

Номер: US20120194894A1
Автор: Satoshi Hayashi, Shigenobu Hirano, Tohru Yashiro, Yousuke Manabe
Принадлежит: Ricoh Co Ltd

Disclosed are electrochromic compounds represented by the formulas defined in the specification.

Подробнее
Номер записи: 10
23-08-2012 дата публикации

Compounds for treatment of cell proliferative diseases

Номер: US20120214850A1
Автор: Alexander Levitzki, Izabela Fokt, Moshe Talpaz, Nicholas Donato, Slawomir Szymanski, Waldemar Priebe
Принадлежит: Individual

The present invention concerns compounds and their use to treat cell proliferative diseases such as cancer. Compounds of the present invention display significant potency as kinase inhibitors, cause the downregulation of c-myc, and inhibit the growth and survival of cancerous cell lines.

Подробнее
Номер записи: 11
13-12-2012 дата публикации

Metal complex, and adsorbent, occlusion material and separator material made from same

Номер: US20120312164A1
Автор: Chikako Ikeda, Koichi Kanehira, Yasutaka Inubushi
Принадлежит: Kuraray Co Ltd

This invention provides a metal complex having a gas adsorption capability, a gas storing capability, and a gas separation capability. The present invention attained the above object by a metal complex comprising: a dicarboxylic acid compound (I) represented by the following General Formula (I), wherein R 1 , R 2 , R 3 , and R 4 are as defined in the specification; at least one metal ion selected from ions of a metal belonging to Group 2 and Groups 7 to 12 of the periodic table; and an organic ligand capable of bidentate binding to the metal ion, the organic ligand belonging to the D ∞h point group, having a longitudinal length of not less than 8.0 Å and less than 16.0 Å, and having 2 to 7 heteroatoms.

Подробнее
Номер записи: 12
14-03-2013 дата публикации

Compounds (cystein based lipopeptides) and compositions as tlr2 agonists used for treating infections, inflammations, respiratory diseases etc.

Номер: US20130065861A1
Автор: Jianfeng Pan, Timothy Z. Hoffman, Tom Yao-Hsiang Wu, Yefen Zou
Принадлежит: IRM LLC

The invention provides a novel class of compounds viz. generally lipopeptides like Pam3CSK4, immunogenic compositions and pharmaceutical compositions comprising such compounds and methods of using such compounds to treat or prevent diseases or disorders associated with Toll-Like Receptors 2. In one aspect, the compounds are useful as adjuvants for enhancing the effectiveness a vaccine.

Подробнее
Номер записи: 13
28-03-2013 дата публикации

Compositions and methods for modulating the wnt signaling pathway

Номер: US20130079328A1
Автор: Dai Cheng, DONG Han, Guobao Zhang, Lichun Shen, Rajender Reddy Leleti, Shifeng Pan, Wenqi Gao
Принадлежит: Individual

The present invention relates to compositions and methods for modulating the Wnt signaling pathway, using compounds having Formula (1) and (3): wherein A, B, Y and Z all represent rings, and R 1 , R 2 , R 3 are as defined herein.

Подробнее
Номер записи: 14
28-03-2013 дата публикации

PYRIDYL-2-METHYLAMINO COMPOUNDS, COMPOSITIONS AND USES THEREOF

Номер: US20130079376A1
Автор: Almassian Bijan, Lin Xu Kevin, Sadowski Martin J.
Принадлежит:

Compounds are provided according to formula I: 2. (canceled)5. (canceled)6. (canceled)7. (canceled)8. The method according to ; wherein R′″ is H.9. The method according to ; wherein Ris H or Me.10. The method according to ; wherein Ris H.11. The method according to ; wherein Ris H.12. The method according to ; wherein Ris H.13. The method according to ; wherein Ris H.16. (canceled)17. (canceled)18. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a pharmaceutically effective amount of .19. (canceled)21. The method according to claim 1 , wherein the medical condition is selected from Alzheimer's disease claim 1 , Down's syndrome claim 1 , and Parkinson's disease.22. (canceled)23. (canceled)24. The method according to claim 1 , wherein the medical condition is associated with modulation of Aβ production.25. The method according to claim 1 , wherein the medical condition is associated with inhibition of Aβ production.26. The method according to claim 1 , wherein the medical condition is associated with modulation of APP expression or APP translation.27. A method for lowering the load of Aβ plaque claim 1 , which comprises administering to the mammal an effective treating amount of a compound according to formula I claim 1 , IVa claim 1 , IVb claim 1 , or V.28. A method for lowering the brain Aβ level claim 1 , which comprises administering to the mammal an effective treating amount of a compound according to formula I claim 1 , IVa claim 1 , IVb claim 1 , or V. The present application claims the benefit under 35 U.S.C. §119 of U.S. Provisional Application Ser. No. 61/505,511, filed Jul. 7, 2011. The content of said provisional application is hereby incorporated by reference in its entirety.Provided herein are pyridylmethylamine compounds with anti-Aβ production, aggregation, inhibition of oxidative stress, and modulation of amyloid precursor protein (APP) translation properties, and pharmaceutical compositions thereof. Also provided are ...

Подробнее
Номер записи: 15
18-04-2013 дата публикации

Method of Synthesizing the Complex [FE(NNS)2] Active Against the Malaria Parasite Plasmodium Falciparum

Номер: US20130096308A1
Автор: Enos Kiremire
Принадлежит: UNIVERSITY OF NAMIBIA

Metal complex of Iron (U) containing a dithio-based ligand have been synthesized and characterized by elemental analysis, mass spectrometry, Proton NMR and FT-ER spectrometry. A single crystal X-ray structure of the cadmium complex has been analyzed. The metal complex was subjected to biological tests on falcipain-2 (FP-2) and falcipain-3 (FP-3) cysteine protease enzymes from the malaria parasite Plasmodium falciparum . They were further tested in vitro against chloroquine resistant strain (W2). Whereas the potency of the metal complexes was weaker than the control regarding the FP-2 and FP-3, the potency of metal complexes was found to be exceedingly greater than the control when tested against the chloroquine resistant strain (W2) with a strength ratio of (0.5). This paper describes the synthesis, characterization and biological results of the said metal complex containing deprotonated 3-[1-(2-pyridyl) ethylidene] hydrazinecarbodithioate ligand (FIG. 1 ).

Подробнее
Номер записи: 16
25-04-2013 дата публикации

Method for the preparation of cis-1,2-diols in the kilogram scale

Номер: US20130102640A1
Автор: Andreas Werner, Georg Stoehr, Werner Mederski
Принадлежит: Merck Patent GmBH

The present invention relates to the scale up of the preparation of cis-1,2-diols of formula I from the gram to the kilogram scale.

Подробнее
Номер записи: 17
09-05-2013 дата публикации

HETEROCYCLIC RING COMPOUND

Номер: US20130116214A1
Автор: Sakai Nozomu, Takakura Nobuyuki, Takami Kazuaki, Ujikawa Osamu
Принадлежит:

The present invention provides a compound having a muscle cell or adipocyte differentiation regulating action, useful for the prophylaxis or treatment of diseases such as diabetes, obesity, dyslipidemia and the like, and the like, and having superior efficacy. 2. The compound or salt of claim 1 , wherein Lis a Calkenylene group.3. The compound or salt of claim 1 , wherein Lis a Calkylene group.4. The compound or salt of claim 1 , wherein A is a benzene ring optionally substituted by 1 to 3 substituents selected from a Calkoxy group and a halogen atom.5. The compound or salt of claim 1 , wherein Y is a bond or —O—.6. The compound or salt of claim 1 , wherein Ris{'sub': '1-6', '(1) imidazolyl, oxadiazolyl or morpholinyl, each of which is optionally substituted by 1 to 3 Calkyl groups,'}{'sub': '1-6', '(2) benzimidazolyl optionally substituted by 1 to 3 Calkyl groups,'}{'sub': 3', '2', '2', '5', '2, 'is (3) —PO(OCH)or —PO(OCH)or'}{'sub': 2', '3, '(4) —S(O)CH.'}7. The compound or salt of claim 1 , wherein Ris imidazol-1-yl claim 1 , benzimidazol-1-yl claim 1 , 1 claim 1 ,3 claim 1 ,4-oxadiazol-2-yl or morpholin-4-yl claim 1 , each of which is optionally substituted by Calkyl group(s).10. (2E)-3-[4-(4-Fluorophenyl)pyridin-3-yl]-N-{4-[2-(1 claim 1 ,3 claim 1 ,4-oxadiazol-2-yl)ethyl]phenyl}prop-2-enamide or a salt thereof.11. (2E)-3-[4-(4-Fluorophenyl)pyrimidin-5-yl]-N-{4-[2-(1 claim 1 ,3 claim 1 ,4-oxadiazol-2-yl)ethyl]phenyl}prop-2-enamide or a salt thereof.12. A medicament comprising the compound or salt of .13. The medicament of claim 12 , which is a muscle cell or adipocyte differentiation regulating agent.14. The medicament of claim 12 , which is an agent for the prophylaxis or treatment of a muscle cell or adipocyte differentiation-associated disease.15. The medicament of claim 12 , which is an agent for the prophylaxis or treatment of diabetes claim 12 , obesity or dyslipidemia.16. A method for the prophylaxis or treatment of diabetes claim 1 , obesity or ...

Подробнее
Номер записи: 18
16-05-2013 дата публикации

INHIBITION OF BACTERIAL BIOFILMS WITH ARYL CARBAMATES

Номер: US20130123225A1
Автор: Melander Christian, Rogers Steven A.
Принадлежит:

Disclosure is provided for carbamate compounds that prevent, remove and/or inhibit the formation of biofilms, compositions including these compounds, devices including these compounds, and methods of using the same. 8. The compound of claim 1 , wherein n=1 to 5.9. The compound of claim 1 , wherein n=1 to 5 claim 1 , saturated.11. A composition comprising a carrier and an effective amount of the compound of .12. A composition comprising the compound of and a biocide.13. A composition comprising the compound of covalently coupled to a substrate.14. The composition of claim 13 , wherein said substrate comprises a polymeric material.15. The composition of claim 13 , wherein said substrate comprises a solid support.16. The composition of claim 13 , wherein said substrate is selected from the group consisting of a drainpipe claim 13 , glaze ceramic claim 13 , porcelain claim 13 , glass claim 13 , metal claim 13 , wood claim 13 , chrome claim 13 , plastic claim 13 , vinyl claim 13 , and laminate.17. The composition of claim 13 , wherein said substrate is selected from the group consisting of shower curtains or liners claim 13 , upholstery claim 13 , laundry claim 13 , and carpeting.18. A biofilm preventing claim 13 , removing or inhibiting coating composition claim 13 , comprising:(a) a film-forming resin;(b) a solvent that disperses said resin;{'claim-ref': {'@idref': 'CLM-00001', 'claim 1'}, '(c) an effective amount of the compound of , wherein said effective amount of said compound inhibits the growth of a biofilm thereon; and'}(d) optionally, at least one pigment.19. The coating composition of claim 18 , wherein said compound is covalently coupled to said resin.20. The coating composition of claim 18 , wherein said resin comprises a polymeric material.21. A substrate coated with the coating composition of .22. A method of controlling biofilm formation on a substrate comprising the step of contacting the compound of to said substrate in an amount effective to inhibit ...

Подробнее
Номер записи: 19
16-05-2013 дата публикации

Aryl urea derivatives as n-formyl peptide receptors like-1 (fprl-1) receptor modulators

Номер: US20130123496A1
Автор: John E. Donello, Michael E. Garst, Richard L. Beard, Tien T. Duong, Veena Viswanath
Принадлежит: Allergan Inc

The present invention relates to novel aryl urea derivatives, processes for preparing them, pharmaceutical compositions containing them and their use as pharmaceuticals as modulators of the N-formyl peptide receptor like-1 (FPRL-1) receptor.

Подробнее
Номер записи: 20
30-05-2013 дата публикации

4-carboxybenzylamino derivatives as histone deacetylase inhibitors

Номер: US20130137690A1
Автор: David J. Witter, Karin M. Otte, Kevin J. Wilson, Matthew G. Stanton, Paul Harrington, Paul Tempest, Phieng Siliphaivanh, Richard W. Heidebrecht, JR., Solomon Kattar, Thomas A. Miller
Принадлежит: Individual

The present invention relates to a novel class of 4-carboxybenzylamino derivatives. The 4-carboxybenzylamino compounds can be used to treat cancer. The 4-carboxybenzylamino compounds can also inhibit histone deacetylase and are suitable for use in selectively inducing terminal differentiation, and arresting cell growth and/or apoptosis of neoplastic cells, thereby inhibiting proliferation of such cells. Thus, the compounds of the present invention are useful in treating a patient having a tumor characterized by proliferation of neoplastic cells. The compounds of the invention may also be useful in the prevention and treatment of TRX-mediated diseases, such as autoimmune, allergic and inflammatory diseases, and in the prevention and/or treatment of diseases of the central nervous system (CNS), such as neurodegenerative diseases. The present invention further provides pharmaceutical compositions comprising the 4-carboxybenzylamino derivatives and safe dosing regimens of these pharmaceutical compositions, which are easy to follow, and which result in a therapeutically effective amount of the 4-carboxybenzylamino derivatives in vivo.

Подробнее
Номер записи: 21
30-05-2013 дата публикации

THERAPEUTIC COMPOUNDS

Номер: US20130137699A1
Автор: Dawson Marcia, Fontana Joseph A., Xia Zebin
Принадлежит:

The invention provides compounds of formula I or a salt thereof as described herein. The invention also provides pharmaceutical compositions comprising a compound of formula I, processes for preparing compounds of formula I, intermediates useful for preparing compounds of formula I and therapeutic methods for inducing apoptosis or treating cancer using compounds of formula I. 2. The compound of wherein Zis N claim 1 , Zis CR claim 1 , Zis CRand Zis N.3. The compound of wherein Zis CR claim 1 , Zis CR claim 1 , Zis CRand Zis N.4. The compound of wherein Ris H or halo.56-. (canceled)7. The compound of wherein Zis CR claim 1 , Zis N claim 1 , Zis CRand Zis N.89-. (canceled)10. The compound of wherein Zis CR claim 1 , Zis CR claim 1 , Zis N and Zis N.1112-. (canceled)13. The compound of wherein Zis CR claim 1 , Zis N claim 1 , Zis CRand Zis CR.1416-. (canceled)17. The compound of wherein Zis CR claim 1 , Zis N claim 1 , Zis N and Zis CR.1819-. (canceled)20. The compound of wherein Ris adamantyl wherein any adamantyl of Rmay be optionally substituted with one or more groups selected from —OH and oxo(═O).2123-. (canceled)24. The compound of claim wherein Ris —OH or —OC(═O)R.2527-. (canceled)28. The compound of wherein Ris H or (C-C)alkoxy.2931-. (canceled)32. The compound of wherein Rand Rtogether with the atoms to which they are attached form a alkylenedioxy ring claim 1 , wherein the alkylenedioxy ring is optionally substituted is with one or more (C-C)alkyl.33. (canceled)34. The compound of wherein A is —CR═CR—.35. (canceled)36. The compound of wherein Ris H or (C-C)alkyl.37. (canceled)39. A composition comprising a compound as described in claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , and a pharmaceutically acceptable diluent or carrier.40. (canceled)41. A method for inducing apoptosis or cell death in a mammal in need of such treatment comprising administering to the mammal an effective amount of a compound as described in claim 1 , or a ...

Подробнее
Номер записи: 22
06-06-2013 дата публикации

Novel hydroxamates as therapeutic agents

Номер: US20130142758A1
Автор: Chitra Baskaran, Erik J. Verner, James Robinson, Joseph J. Buggy, Martin Sendzik
Принадлежит: Pharmacyclics LLC

The present invention is directed to certain hydroxamate derivatives that are useful in the treatment of hepatitis C. These compounds are also inhibitors of histone deacetylase and are therefore useful in the treatment of diseases associated with histone deacetylase activity. Pharmaceutical compositions and processes for preparing these compounds are also disclosed.

Подробнее
Номер записи: 23
06-06-2013 дата публикации

Bis-pyrinidium compounds

Номер: US20130143928A1
Автор: Alfred Werner Widmer, Katrina Anne Jolliffe
Принадлежит: UNIVERSITY OF SYDNEY

A method of treating, inhibiting, or preventing an infection in a subject is described. The method comprises administering to the subject an effective amount of at least one bis-pyridinium compound. The bis-pyridinium compound comprises two aromatic ring structures. Each of the ring structures comprises a pyridine ring, and the ring structures are linked by a linker group of at least 8 atoms in length, said linker group being attached to the nitrogen atoms of the pyridine rings. At least one substituent on at least one of the ring structures is an alkyl group having at least 2 carbon atoms, and no substituent on either of the ring structures is —OH, —SH or an amine group.

Подробнее
Номер записи: 24
13-06-2013 дата публикации

Novel trpv3 modulators

Номер: US20130150409A1
Автор: Arthur Gomtsyan, Bruce Clapham, Eric A. Voight, Erol K. Bayburt, Jerome F. Daanen, Michael E. Kort, Phil B. Cox, Philip R. Kym
Принадлежит: AbbVie Inc

Disclosed herein are modulators of TRPV3 of formula (I) wherein G 1 , X 1 , X 2 , X 3 , X 4 , X 5 , G 2 , Z 1 , R a , R b , u, and p are as defined in the specification. Compositions comprising such compounds and methods for treating conditions and disorders using such compounds and compositions are also presented.

Подробнее
Номер записи: 25
20-06-2013 дата публикации

Trpm8 antagonists and their use in treatments

Номер: US20130158034A1
Автор: Daniel B. Horne, Holger Monenschein, James Brown, Jian J. Chen, Matthew R. Kaller, Nobuko Nishimura, Qingyian Liu, Scott Harried, Thomas T. Nguyen, Vijay Keshav Gore, Wenge Zhong
Принадлежит: AMGEN INC

Compounds of Formula I are useful as antagonists of TRPM8. Such compounds are useful in treating a number of TRPM8 mediated disorders and conditions and may be used to prepare medicaments and pharmaceutical compositions useful for treating such disorders and conditions. Examples of such disorders include, but are not limited to, migraines and neuropathic pain. Compounds of Formula I have the following structure: where the definitions of the variables are provided herein.

Подробнее
Номер записи: 26
20-06-2013 дата публикации

PIPERIDINE DERIVATIVES

Номер: US20130158050A1
Автор: Kolczewski Sabine, Pinard Emmanuel, Stalder Henri
Принадлежит: Hoffmann-La Roche Inc.

The present invention relates to a compound of formula I 2. A compound of claim 1 , wherein Ris lower alkyl.3. A compound of claim 2 , wherein the phenyl group for Ar is substituted by at least two CFgroups.4. A compound of claim 3 , selected from the group consisting ofrac-2-fluoro-N-(1-methyl-3-phenyl-piperidin-3-yl)-4,6-bis-trifluoromethyl-benzamide;rac-2-methoxy-N-(1-methyl-3-phenyl-piperidin-3-yl)-4,6-bis-trifluoromethyl-benzamide;rac-2-ethyl-N-(1-methyl-3-phenyl-piperidin-3-yl)-4,6-bis-trifluoromethyl-benzamide;rac-N-[3-(4-fluoro-phenyl)-1-methyl-piperidin-3-yl]-2-methoxy-4,6-bis-trifluoromethyl-benzamide; and2-methoxy-N—((R)-1-methyl-3-phenyl-piperidin-3-yl)-4,6-bis-trifluoromethyl-benzamide.5. A compound of claim 1 , wherein the phenyl group for Ar is substituted by at least one CFgroup.6. A compound of claim 5 , selected from the group consisting ofrac-2-ethyl-N-(1-methyl-3-phenyl-piperidin-3-yl)-4-trifluoromethyl-benzamide;rac-2-bromo-6-methoxy-N-(1-methyl-3-phenyl-piperidin-3-yl)-4-trifluoromethyl-benzamide;rac-N-(1,2-dimethyl-3-phenyl-piperidin-3-yl)-2-methoxy-6-methylsulfanyl-4-trifluoromethyl-benzamide;rac-2-cyclopropyl-N-(1-methyl-3-phenyl-piperidin-3-yl)-4-trifluoromethyl-benzamide;rac-2-methoxy-N-(1-methyl-3-phenyl-piperidin-3-yl)-6-methylsulfanyl-4-trifluoromethyl-benzamide;rac-N-(1-methyl-3-phenyl-piperidin-3-yl)-2-methylsulfanyl-4-trifluoromethyl-benzamide;rac-N-[3-(4-fluoro-phenyl)-1-methyl-piperidin-3-yl]-2-methoxy-6-methylsulfanyl-4-trifluoromethyl-benzamide;rac-N-[3-(4-chloro-phenyl)-1-methyl-piperidin-3-yl]-2-methoxy-6-methylsulfanyl-4-trifluoromethyl-benzamide;2-methoxy-N-((S)-1-methyl-3-phenyl-piperidin-3-yl)-6-methylsulfanyl-4-trifluoromethyl-benzamide;2-methoxy-N—((R)-1-methyl-3-phenyl-piperidin-3-yl)-6-methylsulfanyl-4-trifluoromethyl-benzamide; andrac-2-difluoromethoxy-N-(1-methyl-3-phenyl-piperidin-3-yl)-4-trifluoromethyl-benzamide.7. A compound of claim 5 , selected from the group consisting ofrac-N-[3-(3-chloro-phenyl)-1-methyl- ...

Подробнее
Номер записи: 27
27-06-2013 дата публикации

SULFUR DERIVATIVES AS CHEMOKINE RECEPTOR MODULATORS

Номер: US20130165460A1
Автор: Beard Richard L., Donello John E., Garst Michael E., Liu Xiaoxia, Viswanath Veena, Yuan Haiqing
Принадлежит: ALLERGAN, INC.

The present invention relates to novel sulfur derivatives, processes for preparing them, pharmaceutical compositions containing them and their use as pharmaceuticals as modulators of chemokine receptors. 2. A compound according to claim 1 , wherein:{'sup': '5', 'Ris S.'}3. A compound according to claim 1 , wherein:{'sup': '5', 'Ris —S(O)—.'}4. A compound according to claim 1 , wherein:{'sup': '5', 'sub': '2', 'Ris —S(O)—.'}5. A compound according to claim 1 , wherein:{'sup': '2', 'Ris methyl, isopropyl, 2-hydroxyethyl, methylpropionate, 2-methylpyridine, 3-methylpyridine, ethylacetate, N,N-dimethylpropanamide, N-isopropylpropanamide, N-(propan-2-yl)propanamide, propanamide hydroxycyclopent-3-yl, ethyl, N,N-dimethylacetamide, N-methylacetamide, 2-aminoethyl, H-imidazol-2-ylmethyl, 1H-imidazol-4-ylmethyl or ethyl-acetamide.'}6. A compound according to claim 1 , wherein:{'sup': '17', 'sub': '1-6', 'Ris H, substituted or unsubstituted Calkyl or halogen;'}{'sup': '18', 'sub': '1-6', 'Ris H, substituted or unsubstituted Calkyl or halogen;'}{'sup': '7', 'sub': 1-6', '1-6', '3-8, 'Ris halogen, CN, —OCalkyl, substituted or unsubstituted Calkyl or substituted or unsubstituted Ccycloalkyl; and'}{'sup': '8', 'sub': '1-6', 'Ris H, substituted or unsubstituted Calkyl or halogen.'}7. A compound according to claim 1 , wherein:{'sup': '17', 'Ris H;'}{'sup': '18', 'Ris H;'}{'sup': '7', 'sub': '1-6', 'Ris halogen, CN or —OCalkyl; and'}{'sup': '8', 'Ris H.'}8. A compound according to claim 1 , wherein:{'sup': '2', 'Ris methyl, isopropyl, 2-hydroxyethyl, methylpropionate, 2-methylpyridine, 3-methylpyridine, ethylacetate, N,N-dimethylpropanamide, N-isopropylpropanamide, N-(propan-2-yl)propanamide, propanamide hydroxycyclopent-3-yl, ethyl, N,N-dimethylacetamide, N-methylacetamide, 2-aminoethyl, H-imidazol-2-ylmethyl, 1H-imidazol-4-ylmethyl or ethyl-acetamide;'}{'sup': '5', 'sub': '2', 'Ris —S—, —S(O)—, or —S(O)—;'}{'sup': '17', 'Ris H;'}{'sup': '18', 'Ris H;'}{'sup': '7', 'sub': '1-6', ' ...

Подробнее
Номер записи: 28
04-07-2013 дата публикации

NOVEL BENZENESULFONAMIDE COMPOUNDS, METHOD FOR SYNTHESIZING SAME, AND USE THEREOF IN MEDICINE AS WELL AS IN COSMETICS

Номер: US20130172363A1
Автор: Chambon Sandrine, CHANTALAT Laurent, Clary Laurence, Pascal Jean-Claude, ROSIGNOLI Carine, ROYE Olivier, Schuppli Marlene
Принадлежит: GALDERMA RESEARCH & DEVELOPMENT

Benzenesulfonamide compounds having a structure of formula (I) are described. Also described, are methods for synthesizing the compounds and to the use thereof in pharmaceutical compositions for human or veterinary medicine and in cosmetic compositions. 1. A compound having the name (S)—N-hydroxy-3-[4-(2-methylquinolin-4-ylmethoxy)benzenesulfonylamino]-2-[4-(propane-2-sulfonyl)piperazin-1-yl]propionamide.2. A composition comprising the compound as claimed in claim 1 , and an acceptable carrier.3. A pharmaceutical composition comprising the compound claim 1 , as claimed in and a pharmaceutically acceptable carrier.5. The compound as claimed in claim 4 , in which{'sub': '4', 'Ris an alkyl radical containing 1 to 4 carbon atoms; and'}{'sub': '3', 'Ris a polycyclic aromatic heterocylic radical containing the heteroatom N;'}and salts thereof, and enantiomers thereof.6. The compound as claimed in claim 4 , wherein the compound is (S)—N-hydroxy-3-[4-(2-methylquinolin-4-ylmethoxy)benzenesulfonylamino]-2-[4-(propane-2-sulfonyl)piperazin-1-yl]propionamide claim 4 , and salts thereof claim 4 , and enantiomers thereof.7. A composition comprising the compound as claimed in claim 4 , or a salt thereof claim 4 , or an enantiomer thereof claim 4 , and an acceptable carrier.8. A pharmaceutical composition comprising the compound as claimed in claim 4 , a salt thereof claim 4 , or an enantiomer thereof claim 4 , and a pharmaceutically acceptable carrier.9. A method of treating an inflammatory skin disease claim 3 , wherein the method comprises administering the pharmaceutical composition as claimed in claim 3 , to a subject in need thereof.10. The method of claim 9 , wherein the inflammatory skin disease is psoriasis or atopic dermatitis.11. A method of treating an inflammatory skin disease claim 8 , wherein the method comprises administering the pharmaceutical composition as claimed in claim 8 , to a subject in need thereof.12. The method of claim 11 , wherein the inflammatory skin ...

Подробнее
Номер записи: 29
04-07-2013 дата публикации

PHENOXYALKYL PYRIDINIUM OXIME THERAPEUTICS FOR TREATMENT OF ORGANOPHOSPHATE POISONING

Номер: US20130172393A1
Автор: Chambers Howard W., Chambers Janice E., Meek Edward C.
Принадлежит:

Phenoxyalkyl pyridinium oxime compounds for use in treating organophosphate poisoning. 2. The composition of claim 1 , wherein R is methyl claim 1 , ethyl claim 1 , phenyl claim 1 , methoxy claim 1 , ethoxy claim 1 , trimethyl claim 1 , methylchloro claim 1 , diethyl claim 1 , diethylchloro claim 1 , ethylchloro claim 1 , phenoxy claim 1 , acetyl claim 1 , benzoyl claim 1 , bromo claim 1 , chloro claim 1 , iodo claim 1 , dichloro claim 1 , or trichloro.3. The composition of claim 1 , wherein R is one of the following substituents:{'sub': '3', '4-CH—;'}{'sub': 3', '2', '2, '2,6-([CH]CH)—;'}{'sub': '3', '4-CH—O;'}4-Cl—;4-Br—;{'sub': '2', '4-ON—;'}{'sub': '2', '3-ON—;'}{'sub': '3', '4-CHCO—;'}{'sub': 3', '2, '4-CHCHCO—;'}3-CHCH═CHCH-4;4-Ph;{'sub': 3', '3, '2,3,5-(CH)—;'}{'sub': 3', '3, '2,4,6-(CH)—;'}{'sub': '3', '3-CH-4-Cl—;'}4-Ph-CO—;{'sub': '2', '2,5-Cl—;'}4-Ph-O—;{'sub': '2', '4-Ph-CH—;'}{'sub': '2', '4,Ph-CH—O—;'}{'sub': '3', '2,4,5-Cl)—;'}{'sub': '2', '4-Ph-CHCO—;'}{'sub': '3', '2,4,6-Cl—;'}{'sub': '2', '3,4-Cl—;'}{'sub': 2', '2, '2,6-Cl-4-ON—;'}{'sub': 3', '2, '4-Cl-3,5-(CH)—;'}3-Ph-;{'sub': 3', '2, '3-CHCH-4-Cl—;'}{'sub': '3', '3-O—C(:O)—CH═C(CH)-4;'}{'sub': 3', '3', '3, '2-CH-4-(CH)C—;'}{'sub': 3', '3', '2, '2,4-[(CH)C—]—;'}{'sub': 3', '2', '3', '2, '4-CHCHC(CH)—;'}{'sub': 3', '3', '2', '2', '2, '4-(CH)CCHC(CH)—;'}2-Br-4-Cl—;2-Cl-4-Br—;{'sub': '3', '2-Br-4-CH—;'}{'sub': 3', '2, '4-Br-3,5-(CH)—;'}{'sub': 3', '2', '6, '4-CH(CH)—O—;'}{'sub': 3', '2, '4-Ph-C(CH)—;'}{'sub': 3', '2', '2, '4-CH—O—CHCH—; or'}{'sub': '2', '2,4-Cl—.'}43. The composition of any of - claims 1 , wherein X is halo claims 1 , optionally bromo.54. The composition of any of - claims 1 , wherein the composition comprises a pharmaceutically acceptable excipient in combination with the compound.65. A method of reactivating phosphorylated brain acetylcholinesterase that has been inhibited by at least one organophosphorous compound claims 1 , the method comprising administering to a subject in need ...

Подробнее
Номер записи: 30
04-07-2013 дата публикации

METHOD FOR OXIDIZING ALCOHOLS

Номер: US20130172543A1
Автор: HAYASHI Masaki, IWABUCHI Yoshiharu
Принадлежит: TOHOKU UNIVERSITY

A method for oxidizing an alcohol, wherein oxidation is performed in the presence of a compound represented by the following formula (I) and a bulk oxidant, which enables efficient oxidation of secondary alcohols as well as primary alcohols, and can attain high reaction efficiency even when air is used as a bulk oxidant. 2. The method according to claim 1 , wherein the alcohol is a secondary alcohol.3. The method according to claim 1 , wherein the bulk oxidant is a peracid claim 1 , hydrogen peroxide claim 1 , a hypohalogen acid or a salt thereof claim 1 , a perhalogen acid or a salt thereof claim 1 , a persulfuric acid salt claim 1 , a halogenating agent such as a halide and N-bromosuccinimide claim 1 , a trihalogenated isocyanuric acid claim 1 , a diacetoxyiodoallene claim 1 , a dialkyl azodicarboxylate claim 1 , oxygen claim 1 , air claim 1 , or a mixture thereof.4. The method according to claim 1 , wherein the bulk oxidant is air.5. The method according to claim 2 , wherein the bulk oxidant is a peracid claim 2 , hydrogen peroxide claim 2 , a hypohalogen acid or a salt thereof claim 2 , a perhalogen acid or a salt thereof claim 2 , a persulfuric acid salt claim 2 , a halogenating agent such as a halide and N-bromosuccinimide claim 2 , a trihalogenated isocyanuric acid claim 2 , a diacetoxyiodoallene claim 2 , a dialkyl azodicarboxylate claim 2 , oxygen claim 2 , air claim 2 , or a mixture thereof.6. The method according to claim 2 , wherein the bulk oxidant is air. The present invention relates to a method for oxidizing an alcohol utilizing an organic catalyst.Oxidation reactions of alcohols constitute one class of important reactions as methods for chemical conversion of compounds, and are frequently used in syntheses of organic compounds with high added values such as medicaments and agricultural chemicals and the like. Therefore variety of methods have been developed so far. However, many of those methods use explosive reagents, highly toxic metals and the ...

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

Cannabinoid receptor modulators

Номер: US20130178457A1
Автор: Amolsing Dattu PATIL, Chaitanya Prabhakar Kulkarni, Narasimha Murthy Cheemala, Nirmal Kumar Jana, Prashant Popatrao Vidhate, Prashant Vitthalrao TALE, Rajender Kumar Kamboj, Rohan Mahadev SHINDE, Sachin Jaysing Mahangare, Sachin MADAN, Sanjeev Anant Kulkarni, Sapana Suresh PATEL, Seema Prabhakar ZADE, Venkata P. Palle
Принадлежит: Lupin Ltd

Compounds of Formula (I) along with processes for their preparation that are useful for treating, managing and/or lessening the diseases, disorders, syndromes or conditions associated with the modulation of cannabinoid (CB) receptors. Methods of treating, managing and/or lessening the diseases, disorders, syndromes or conditions associated with the modulation of cannabinoid (CB) receptors of Formula (I).

Подробнее
Номер записи: 32
25-07-2013 дата публикации

ACYLATION REACTION OF HYDROXYL GROUP

Номер: US20130190502A1
Автор: Iwasaki Takanori, Mashima Kazushi, OHSHIMA Takashi, Sayo Noboru
Принадлежит: TAKASAGO INTERNATIONAL CORPORATION

Disclosed is a selective ester production process of an alcoholic hydroxyl group, which proceeds under chemically mild conditions, while having adequate environmental suitability, operability and economical efficiency. Specifically disclosed is a process for producing an ester compound, which is characterized in that an alcohol and a carboxylic acid ester compound are reacted in the presence of a compound containing zinc element, thereby selectively acylating a hydroxyl group of the alcohol. 14.-. (canceled)5. A process for producing an ester compound comprising reacting a mixture of an alcohol and an amine with a carboxylic acid ester in the presence of a compound containing a zinc element , thereby selectively acylating a hydroxyl group of the alcohol. The present invention provides a process for producing an ester compound by performing a transesterification reaction in the presence of a catalyst containing zinc element.Ester compounds are abundantly found in nature, as well as in medicines, agrochemicals, perfumes, functional materials and the like. In the syntheses of these materials, reactions between corresponding alcohols and carboxylic acids, carboxylic acid chlorides, carboxylic acid anhydrides and the like, or trans-esterification reactions making use of ester compounds are widely used. A series of methods play an important role not only for the purpose of producing ester compounds, but also as a method for protecting a hydroxyl group or a carboxyl group.A method of using an ester compound derived from a low boiling point alcohol as an acylating agent (transesterification reaction) can be said to be a technique excellent in operability and economic efficiency from the aspect that obtainment (preparation) and handling of the acylating agent are easy, and also that separation of the target product can be carried out in a short step. There have been developed, as the transesterification reaction, classical methods of using a protic acid, as well as many ...

Подробнее
Номер записи: 33
25-07-2013 дата публикации

Functionalized Polymers Using Protected Thiols

Номер: US20130190504A1
Автор: DAVID Ralph L., KORNFIELD Julia A.
Принадлежит:

A process for the preparation of functional molecules using the thiol-ene coupling reaction and a process for the preparation of protected functional thiols, specifically thioesters is provided. The methods may be used to make functional polymers and other molecules. The method of making a functionalized polymer using a thiol-ene reaction comprises: providing a functionalized thioester having the following formula: 1. A functionalized thioester made by a method of preparing a functionalized thioester comprising:(a) reacting a nucleophilic starting material having a desired functional group with a nonsymmetrical bifunctional linker molecule, forming a functionalized intermediate; and (b) reacting the functionalized intermediate with a thiol acid to form a functionalized thioester.3. The functionalized thioester of claim 2 , wherein the protecting group is an acetyl or benzoyl group.4. The functionalized thioester of claim 2 , wherein the functional group is selected from the group consisting of: amino acid claim 2 , peptide claim 2 , polypeptide claim 2 , nucleic acid claim 2 , lipid claim 2 , carbohydrate claim 2 , carbazole claim 2 , benzoate claim 2 , phenol claim 2 , pyridine claim 2 , cyanobiphenyl claim 2 , perfluorocarbon claim 2 , polyethylene oxide (PEO) and polypropyleneoxide (PPO) groups This application is a divisional of application Ser. No. 12/961,136, filed Dec. 6, 2010, which is a divisional of application Ser. No. 12/251,708, filed Oct. 15, 2008, which takes priority from U.S. provisional application Ser. No. 60/998,980, filed Oct. 15, 2007, hereby incorporated by reference.Not applicable.This invention relates to functional polymers and functional protected thiol compounds, methods of preparation and use.Functionalization of polymers having pendant vinyl groups using thiol-ene coupling is a powerful and versatile method to prepare well-defined polymeric materials with tailored properties. However, commercially available mercaptans are limited to a ...

Подробнее
Номер записи: 34
01-08-2013 дата публикации

CYCLOPROPYLAMINE DERIVATIVES USEFUL AS LSD1 INHIBITORS

Номер: US20130197013A1
Автор: Estiarte-Martinez Maria de Los Angeles, Fyfe Mathew Colin Thor, Laria Julio Castro-Palomino, Muñoz Alberto Ortega, Pedemonte Marc Martinell, Vidal Nuria Valls
Принадлежит:

The invention relates to cyclopropylamine compounds, in particular the compounds of Formula (I), and their use in therapy, including e.g. in the treatment or prevention of cancer, a neurological disease or condition, or viral infection. 4. The compound of wherein (G) is a heterocyclyl.5. (canceled)6. The compound of wherein (G) is phenyl.78-. (canceled)9. The compound of wherein E is —X═X— claim 1 , and X claim 1 , X claim 1 , Xand Xare independently C(R2) or N.10. The compound of wherein E is —X═X— claim 1 , and X claim 1 , X claim 1 , Xand Xare independently C(R2).1112-. (canceled)13. The compound of wherein E is —S— claim 1 , and Xand Xare independently C(R2) or N.1420-. (canceled)21. The compound of wherein each (R1) is independently chosen from alkyl claim 1 , aryl claim 1 , amino claim 1 , amido claim 1 , nitro claim 1 , halo claim 1 , haloalkyl claim 1 , haloalkoxy claim 1 , cyano claim 1 , heterocycle claim 1 , sulfonyl claim 1 , sulfonamide claim 1 , hydroxyl claim 1 , or alkoxy.22. The compound of wherein each (R1) is independently chosen from —CF claim 1 , —F claim 1 , —Cl claim 1 , —CN claim 1 , —CH claim 1 , —OH claim 1 , —OCH claim 1 , —C(═O)NH claim 1 , —NH—CO—CH claim 1 , —NH—SO—CH claim 1 , —NH—SO—CH—CH claim 1 , —NH—SO—CH(CH)—CH claim 1 , —NH—SO—(CH) claim 1 , —NH—SO—(CH)—CN claim 1 , —NHSOCF claim 1 , or —S(═O)NHCH.2328-. (canceled)30. The compound of wherein E is —S— or —X═X—.3137-. (canceled)38. The compound of wherein (G) is an aryl or heterocyclyl.3941-. (canceled)42. The compound of wherein each (R1) is independently chosen from alkyl claim 29 , aryl claim 29 , amino claim 29 , amido claim 29 , nitro claim 29 , halo claim 29 , haloalkyl claim 29 , cyano claim 29 , heterocyclyl claim 29 , sulfonyl claim 29 , sulfonamide claim 29 , hydroxyl claim 29 , or alkoxy.4446-. (canceled)47. The compound of wherein (G) is an aryl or heterocyclyl.4850-. (canceled)51. The compound of wherein each (R1) is independently chosen from alkyl claim 43 , aryl ...

Подробнее
Номер записи: 35
01-08-2013 дата публикации

HDAC INHIBITORS

Номер: US20130197042A1
Автор: Davidson Alan Hornsby, DAY Francesca Ann, DONALD Alastair David Grahm, MOFFAT David Charles Festus
Принадлежит:

Compounds of formula (I) inhibit HDAC activity: 2. A compound as claimed in claim 1 , wherein W is —CHCH—.3. A compound as claimed in wherein claim 1 , in the radical RRCHNHYLX[CH]— claim 1 , Y is a bond.4. A compound as claimed in wherein claim 1 , in the radical RRCHNHYLX[CH]— claim 1 , Xis a bond.5. A compound as claimed in wherein the radical —YLX[CH]— is —CH—.6. A compound as claimed in wherein Ris methyl claim 1 , ethyl claim 1 , n- or iso-propyl claim 1 , n- claim 1 , sec- or tert-butyl claim 1 , cyclohexyl claim 1 , allyl claim 1 , phenyl claim 1 , benzyl claim 1 , 2- claim 1 , 3- or 4-pyridylmethyl claim 1 , N-methylpiperidin-4-yl claim 1 , tetrahydrofuran-3-yl or methoxyethyl.7. A compound as claimed in wherein Ris cyclopentyl.8. A compound as claimed in wherein Ris phenyl claim 1 , benzyl claim 1 , phenylethyl claim 1 , tert-butoxymethyl or iso-butyl.9. A compound as claimed in wherein Ris —CH(CH) claim 1 , cyclohexyl claim 1 , —CHO(t-Bu) claim 1 , —CHS(t-Bu) claim 1 , or phenyl.11. A compound as claimed in claim 1 , wherein the term ‘substituted’ as applied to any moiety means substituted with up to four (C-C) alkyl groups.12. A compound as claimed in claim 10 , wherein{'sub': 2', '2, 'W is —CHCH—;'}{'sub': 1', '9', '9', '20', '21', '22, 'Ris an ester group which is hydrolysable by one or more intracellular carboxyesterase enzymes to a carboxylic acid group, wherein the ester group is of formula —(C═O)ORwherein Ris RRRC wherein'}{'sub': 20', '1', '3', 'a', '1', '3', 'b', '2', '3', 'a', '1', '3', 'b', 'C', 'C', '1', '3', '21', '22', '1', '3, 'sup': 1', '1', '1, '(i) Ris hydrogen or optionally substituted (C-C)alkyl-(Z)-[(C-C)alkyl]— or (C-C)alkenyl-(Z)-[(C-C)alkyl]— wherein a and b are independently 0 or 1 and Zis —O—, —S—, or —NR— wherein Ris hydrogen or (C-C)alkyl; and Rand Rare independently hydrogen or (C-C)alkyl-;'}{'sub': 20', '12', '13', '1', '3', '12', '1', '3', '13', '1', '3', '12', '13', '21', '22', '1', '3, '(ii) Ris hydrogen or optionally ...

Подробнее
Номер записи: 36
08-08-2013 дата публикации

STABLE INSECTICIDE COMPOSITIONS AND METHODS FOR PRODUCING SAME

Номер: US20130203691A1
Автор: Boucher, JR. Raymond E., Qin Kuide
Принадлежит: Dow AgroSciences, LLC

Insect controlling compositions including an N-substituted (6-haloalkylpyridin-3-yl)alkyl sulfoximine compound exhibiting increased stability, along with methods for preparing same, are disclosed. 4. The method of claim 1 , wherein X represents NOor CN claim 1 , Y represents —CF claim 1 , and Rand Rindependently represent hydrogen claim 1 , methyl or ethyl.5. The method of claim 1 , wherein the composition further includes a spinosyn selected from the group consisting of spinetoram claim 1 , spinosad and mixtures thereof.6. The method of claim 1 , which further includes claim 1 , subsequent to said heating claim 1 , applying to a locus where control is desired an insect-inactivating amount of the composition.7. The method of claim 1 , wherein the heating is performed at a minimum of about 50° C. from about four to about seventy two hours.9. The method of claim 8 , wherein the heating is performed at a minimum of about 50° C. from about four to about seventy two hours.10. The method of claim 8 , wherein the composition includes a spinosyn selected from the group consisting of spinetoram claim 8 , spinosad and mixtures thereof.11. The method of claim 8 , wherein X represents NOor CN claim 8 , Y represents —CFand Rand Rindependently represent hydrogen claim 8 , methyl or ethyl.12. A composition claim 8 , comprising a stereoisomeric mixture of {1-[6-(trifluoromethyl)pyridin-3-yl]ethyl}(methyl)oxido-λ-sulfanylidenecyanamide defined by a first pair of diastereomers and a second pair of diastereomers claim 8 , wherein the first and second pairs of diastereomers are present at a ratio of at least about 3:1.13. The composition of claim 12 , wherein the first and second pairs of diastereomers are present at a ratio from about 3:1 to about 100:1.14. The composition of claim 12 , wherein the first and second pairs of diastereomers are present at a ratio from about 3:1 to about 40:1.15. The composition of claim 12 , wherein the first pair of diastereomers is defined by {(R)-1-[6 ...

Подробнее
Номер записи: 37
08-08-2013 дата публикации

INHIBITORS OF HUMAN IMMUNODEFICIENCY VIRUS REPLICATION

Номер: US20130203747A1
Автор: Bailey Murray D., Bilodeau Francois, Carson Rebekah, Fader Lee, Kawai Stephen, Laplante Steven R., Morin Sebastien, Simoneau Bruno, Surprenant Simon, Thibeault Carl, Tsantrizos Youla S., Yoakim Christiane
Принадлежит: Gilead Sciences, Inc.

Compounds of formula I: 6. A compound according to claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris (C)alkyl claim 1 , —CN claim 1 , halo or (C)haloalkyl.7. A compound according to claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris —CH.11. A pharmaceutical composition comprising a compound of formula (I) according to any one of to claim 1 , or a pharmaceutically acceptable salt thereof; and one or more pharmaceutically acceptable carriers.12. A method of treating HIV infection which comprises administering to a host infected by HIV a therapeutically effective amount of a compound of formula (I) according to any one of to claim 1 , or a pharmaceutically acceptable salt thereof. This application claims benefit of U.S. Ser. No. 61/178,551, filed May 15, 2009, and U.S. Ser. No. 61/285,766, filed Dec. 11, 2009, which are herein incorporated by reference.The present invention relates to compounds, compositions and methods for the treatment of human immunodeficiency virus (HIV) infection. In particular, the present invention provides novel inhibitors of the HIV integrase enzyme, pharmaceutical compositions containing such compounds and methods for using these compounds to reduce HIV replication and in the treatment of HIV infection.Acquired immune deficiency syndrome (AIDS) is caused by the human immunodeficiency virus (HIV), particularly the HIV-1 strain. Most currently approved therapies for HIV infection target the viral reverse transcriptase and protease enzymes. There are also two approved drugs targeting HIV entry and one approved drug targeting the integrase enzyme. Within the reverse transcriptase inhibitor and protease inhibitor classes, resistance of HIV to existing drugs is a problem. Therefore, it is important to discover and develop new antiretroviral compounds.International patent application WO 2007/131350 and United States published patent application US 2006/0106070 describe compounds which are active ...

Подробнее
Номер записи: 38
08-08-2013 дата публикации

NOVEL SYNTHESIS FOR THIAZOLIDINEDIONE COMPOUNDS

Номер: US20130204004A1
Автор: Larsen Scott D., Parker Timothy, Tanis Steven P., Zeller James R.
Принадлежит: Metabolic Solutions Development Company, LLC

The present invention provides novel methods for synthesizing PPARγ sparing compounds, e.g., thiazolidinediones, that are useful for preventing and/or treating metabolic disorders such as diabetes, obesity, hypertension, and inflammatory diseases. 2. The process of claim 1 , wherein X is a leaving group selected from —Br claim 1 , —Cl claim 1 , —I claim 1 , —OMs claim 1 , —OTs claim 1 , —OTf claim 1 , —OBs claim 1 , —ONs claim 1 , —O-tresylate claim 1 , or —OPO(OR) claim 1 , wherein each Ris independently Calkyl or two of Rtogether with the oxygen and phosphorous atoms to which they are attached form a 5-7 membered ring.7. (canceled)10. The process of claim 4 , wherein the compound of Formula 5A is treated with a Grignard reagent and reacted with compound of Formula 6A to form a compound of Formula 2B.11. The process of claim 10 , wherein the Grignard reagent comprises i-PrMgBr.12. The process of claim 4 , wherein X and Xare independently selected from —Br and —Cl.16. The process of claim 14 , wherein each of Rand R′is independently selected from —H claim 14 , —OH claim 14 , or optionally substituted alkoxy; or Rand R′together form oxo claim 14 , Rand R′together form —O(CH)O— claim 14 , wherein n is 2 or 3 claim 14 , or Rand R′together form —S(CH)S— claim 14 , wherein m is 2 or 3.17. The process of claim 16 , wherein Rand R′together form oxo.19. The process of claim 18 , wherein Ris a Calkoxy optionally substituted with 1-3 halo.20. The process of claim 19 , wherein Ris selected from methoxy claim 19 , ethoxy claim 19 , or propoxy claim 19 , any of which is optionally substituted with 1-3 halo.26. (canceled)32. The process of claim 31 , wherein X is a leaving group selected from —Br claim 31 , —Cl claim 31 , —I claim 31 , —OMs claim 31 , —OTs claim 31 , —OTf claim 31 , —OBs claim 31 , —ONs claim 31 , —O-tresylate claim 31 , or —OPO(OR) claim 31 , wherein each Ris independently Calkyl or two of Rtogether with the oxygen and phosphorous atoms to which they are ...

Подробнее
Номер записи: 39
15-08-2013 дата публикации

Compositions for Modulating a Kinase Cascade and Methods of Use Thereof

Номер: US20130210822A1
Автор: CODY Jeremy A., Hangauer, ISBESTER Paul K., JR. David G., PALMER Grant J., PATRA Debasis, SALSBURY Jonathon
Принадлежит: KINEX PHARMACEUTICALS, LLC

The invention relates to compositions comprising 2-(5-(4-(2-morpholinoethoxy)phenyl)pyridin-2-yl)-N-benzylacetamide and its mesylate and dihydrochloride salts. The invention provides an efficient process for the synthesis of 2-(5-(4-(2-morpholinoethoxy)phenyl)pyridin-2-yl)-N-benzylacetamide and its mesylate and dihydrochloride salts and methods for modulating one or more components of a kinase cascade using the compositions of the invention. The present invention also provides a novel polymorph of the mesylate salt of 2-(5-(4-(2-morpholinoethoxy)phenyl)pyridin-2-yl)-N-benzylacetamide (Form A), characterized by a unique X-ray diffraction pattern and Differential Scanning calorimetry profile, as well as a unique crystalline structure. 1. A polymorph of the mesylate salt of 2-(5-(4-(2-morpholinoethoxy)phenyl)pyridin-2-yl)-N-benzylacetamide (Form A) characterized by an X-ray diffraction pattern substantially similar to that set forth in .2. A polymorph of the mesylate salt of 2-(5-(4-(2-morpholinoethoxy)phenyl)pyridin-2-yl)-N-benzylacetamide (Form A) characterized by an X-ray diffraction pattern including peaks at about 22.7 , 19.7 , 18.9 and 16.3 degrees 2θ.3. A polymorph of the mesylate salt of 2-(5-(4-(2-morpholinoethoxy)phenyl)pyridin-2-yl)-N-benzylacetamide (Form A) characterized by a Differential Scanning Calorimetry (DSC) thermogram having a single maximum value at about 164 , as measured by a Mettler 822DSC instrument.4. The polymorph according to claim 1 , further characterized by a Differential Scanning Calorimetry (DSC) thermogram having a single maximum value at about 164 claim 1 , as measured by a Mettler 822DSC instrument.5. The polymorph according to claim 2 , further characterized by a Differential Scanning Calorimetry (DSC) thermogram having a single maximum value at about 164 claim 2 , as measured by a Mettler 822DSC instrument.6. The polymorph of produced by a purification process comprising the step of recrystallizing a crude preparation of said salt ...

Подробнее
Номер записи: 40
22-08-2013 дата публикации

NOVEL METHYLCYCLOHEXANE DERIVATIVES AND USES THEREOF

Номер: US20130217686A1
Автор: Bae Sung Jin, Chae Sang Mi, Hwang Sun Gwan, Jeong Mo Ses, Park Joo Young, Ryu Eun Ju, Yi Han Ju, Yoon Yeo Jin
Принадлежит: SK BIOPHARMACEUTICALS CO., LTD.

A novel methylcyclohexane derivative, and a pharmaceutical composition including the same that is effective for the prevention or treatment of pain. 16.-. (canceled)91. A pharmaceutical composition for the prevention or treatment of pain , the pharmaceutical composition comprising: a therapeutically effective amount of the methylcyclohexane derivative of claim ; and a pharmaceutically acceptable carrier.10. The pharmaceutical composition of claim 9 , wherein the pain is acute pain or chronic pain.11. The pharmaceutical composition of claim 9 , wherein the pain is selected from the group consisting of cancer pain claim 9 , labor pain claim 9 , colic pain claim 9 , neuropathic pain claim 9 , postoperative pain claim 9 , diabetic pain claim 9 , post-herpetic pain claim 9 , inflammatory disease pain claim 9 , muscle pain claim 9 , arthrodynia pain claim 9 , a headache claim 9 , and periodontal disease pain.12. A method of treating pain claim 9 , the method comprising contacting the pharmaceutical composition of and a subject.13. The method of claim 12 , wherein the pain is acute pain or chronic pain.14. The method claim 12 , wherein the pain is selected from the group consisting of cancer pain claim 12 , labor pain claim 12 , colic pain claim 12 , neuropathic pain claim 12 , postoperative pain claim 12 , diabetic pain claim 12 , post-herpetic pain claim 12 , inflammatory disease pain claim 12 , muscle pain claim 12 , arthrodynia pain claim 12 , a headache claim 12 , and periodontal disease pain. This application claims the benefit of Korean Patent Application No. 10-2010-0094463, filed on Sep. 29, 2010, in the Korean Intellectual Property Office, the disclosure of which is incorporated herein in its entirety by reference.The present invention relates to novel methylcyclohexane derivatives and pharmaceutical compositions including the same.Nitric oxide (NO) is a signal transduction molecule that is present in a gaseous phase in vivo and functions as a critical messenger ...

Подробнее
Номер записи: 41
22-08-2013 дата публикации

Arylsulfonamide ccr3 antagonists

Номер: US20130217687A1
Автор: Jared Andrew Forrester, Tai Wei Ly
Принадлежит: Axikin Pharmaceuticals Inc

Provided herein are arylsulfonamides that are useful for modulating CCR3 activity, and pharmaceutical compositions thereof. Also provided herein are methods of their use for treating, preventing, or ameliorating one or more symptoms of a CCR3-mediated disorder, disease, or condition.

Подробнее
Номер записи: 42
22-08-2013 дата публикации

CYCLIC AMIDE DERIVATIVE

Номер: US20130217692A1
Автор: FUJIWARA Hiroaki, Horiuchi Yoshihiro, Iwata Mitsutaka, SASAKI Izumi, Sawamura Kiyoto, Suda Hitoshi
Принадлежит: DAINIPPON SUMITOMO PHARMA CO., LTD.

Provided is a compound represented by formula (1) or a pharmacologically acceptable salt thereof. (In the formula, A is Carylene, etc.; R, Rand Reach independently is a hydrogen atom, a halogen atom, a Calkyl group, a Calkoxy group, etc.; Ris an optionally substituted Caryl group, an optionally substituted 5- to 12-membered monocyclic or polycyclic heteroaryl group, an optionally substituted Caralkyl group, etc.; m is 0, etc.; n is an integer of 0 to 2.) 2. The compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein A is 1 claim 1 ,3-phenylene claim 1 , or 1 claim 1 ,4-phenylene.3. The compound of claim 2 , or a pharmaceutically acceptable salt thereof claim 2 , wherein A is 1 claim 2 ,4-phenylene.6. The compound of claim 5 , or a pharmaceutically acceptable salt thereof claim 5 , wherein Ris(1) halogen atom,(2) cyano group,{'sub': '1-4', 'claim-text': (a) 1 to 3 halogen atom(s), or', {'sub': '1-4', '(b) Calkoxy (in which the group may be optionally substituted by 1 to 3 halogen atom(s))),'}], '(3) Calkyl group (in which the group may be optionally substituted by'}{'sub': '1-4', 'claim-text': (a) 1 to 3 halogen atom(s), or', {'sub': '1-4', '(b) Calkoxy (in which the group may be optionally substituted by 1 to 3 halogen atom(s))),'}], '(4) Calkoxy group (in which the group may be optionally substituted by'}{'sub': '3-6', '(5) Ccycloalkyl group,'}{'sub': '3-6', '(6) Ccycloalkoxy group,'}(7) heterocyclic oxy group, or{'sub': '7-16', '(8) Caralkyloxy group.'}7. The compound of claim 6 , or a pharmaceutically acceptable salt thereof claim 6 , wherein Ris Calkyl group which may be optionally substituted by Calkoxy.8. The compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris(1) hydrogen atom,{'sub': '1-4', '(2) Calkyl group,'}{'sub': '1-4', '(3) Calkoxy group, or'}{'sub': '3-6', '(4) Ccycloalkyl group.'}9. The compound of claim 8 , or a pharmaceutically acceptable salt thereof claim 8 , wherein Ris hydrogen ...

Подробнее
Номер записи: 43
22-08-2013 дата публикации

Non-Flushing Niacin Analogues, and Methods of Use Thereof

Номер: US20130217714A1
Автор: Bachovchin William W., Lai Hung-sen
Принадлежит: TRUSTEES OF TUFTS COLLEGE

One aspect of the present invention relates to substituted pyridines and pharmaceutically acceptable salts thereof that are active against a range of mammalian maladies. Another aspect of the invention relates to a pharmaceutical composition, comprising a compound of the present invention or a pharmaceutically acceptable salt thereof; and a pharmaceutically acceptable excipient. The present invention also relates to methods of treating a range of mammalian maladies or conditions, including but not limited to hyperlipidemia, hypercholesterolemia, atherosclerosis, coronary artery disease, congestive heart failure, cardiovascular disease, hypertension, coronary heart disease, angina, pellagra, Hartnup's syndrome, carcinoid syndrome, arterial occlusive disease, obesity, hypothyroidism, vasoconstriction, osteoarthritis, rheumatoid arthritis, diabetes, Alzheimer's disease, lipodystrophy, or dyslipidemia, raising serum high-density lipoprotein (HDL) levels, and lowering serum low-density lipoprotein (LDL) levels. 184-. (canceled)86. The method of claim 85 , wherein R represents independently for each occurrence H claim 85 , fluoride claim 85 , chloride claim 85 , cyano claim 85 , methyl claim 85 , or ethyl.87. The method of claim 85 , wherein R represents independently for each occurrence H.88. The method of claim 85 , wherein R′ represents independently for each occurrence H claim 85 , alkyl claim 85 , alkenyl claim 85 , alkynyl claim 85 , aryl claim 85 , heteroaryl claim 85 , aralkyl claim 85 , or heteroaralkyl; or the two instances of R′ taken together represent —(CH)— claim 85 , —(CH)— claim 85 , —(CH)— claim 85 , —(CH)— claim 85 , or —(CH)—.89. The method of claim 85 , wherein the two instances of R′ taken together represent —(CH)— claim 85 , —(CH)— claim 85 , —(CH)— claim 85 , —(CH)— claim 85 , or —(CH)—.90. The method of claim 85 , wherein the two instances of R′ taken together represent —(CH)—.91. The method of claim 85 , wherein R″ represents H claim 85 , alkyl ...

Подробнее
Номер записи: 44
19-09-2013 дата публикации

NITRILE DERIVATIVES AND THEIR PHARMACEUTICAL USE AND COMPOSITIONS

Номер: US20130245062A1
Автор: MENON KRISHNA
Принадлежит: CELLCEUTIX CORPORATION

Disclosed are nitrile derivatives and pharmaceutical compositions comprising nitrile derivatives. The pharmaceutical compositions comprise compounds of the formula I 2. A method according to claim 1 , wherein the compound is one wherein Z is sulphur.4. A method according to claim 1 , with the proviso that said composition does not contain S-cyanomethylisothiourea HBr.5. A method according to claim 1 , wherein the compound is selected from S-(3-cyanopropyl)isothiourea claim 1 , S-(2-cyanoethyl)isothiourea claim 1 , S-(4-cyanobutyl)isothiourea claim 1 , S-(5-cyanopentyl)isothiourea claim 1 , S-(4-cyanomethylphenyl)methylisothiourea claim 1 , S-2(4-[2-cyanoethyl]phenyl)ethylisothiourea claim 1 , S-(2-cyanomethylphenyl)methylisothiourea claim 1 , S-(6-cyanomethylpyridin-2-yl)methylisothiourea claim 1 , S-(3-cyanomethylphenyl)methylisothiourea claim 1 , S-(1-cyanomethylnaphth-2-yl))methylisothiourea claim 1 , and their pharmaceutically acceptable salts.6. A method according to claim 1 , wherein the hyperproliferative disease is cellular hyperproliferation such as cancer.7. A method according to claim 6 , wherein said hyperproliferative disease is selected from resistant non-small cell lung cancer claim 6 , breast cancer claim 6 , colon cancer claim 6 , squamous cell carcinoma cancer claim 6 , prostate cancer claim 6 , head and neck cancer and glioma.8. A method according to claim 6 , wherein said medicament is administered prior to radiation treatment.9. A method according to claim 1 , wherein said medicament is for treatment of a condition selected from inflammatory diseases claim 1 , viral infections or bacterial infections.10. A method according to claim 1 , wherein said medicament is formulated for administration of a dose of 200 mg/kg three times per week.11. A method according to claim 1 , wherein said medicament is for use in conjunction with 5-FU.12. A pharmaceutical composition comprising a compound as specified in .13. A pharmaceutical composition according to ...

Подробнее
Номер записи: 45
19-09-2013 дата публикации

PROCESS FOR CYCLOOXYGENASE-2 SELECTIVE INHIBITOR

Номер: US20130245272A1
Автор: Jariwala Viral Narendra, Mistry Ashokkumar Bhikhubhai, Shah Dharmesh Mahendra, Solanki Sanjay Amratlal, Vyas Ashok Vasantray
Принадлежит: Virdev Intermediates PVT. Ltd.

The present invention describes a process for preparing a cyclooxygenase-2 selective inhibitor. It provides a synthetic procedure for the said substance namely 5-chloro-3-(4-methylsulphonyl)phenyl-2-(2-methyl-5-pyridinyl)pyridine of formula (I). The invention also relates to preparation of a new intermediate of formula (IV) and a process to prepare it. Furthermore, the invention describes a process for preparing another key intermediate of formula (II). Compounds of formula (IV) and formula (II) are useful intermediates in synthesis of the said cyclooxygenase-2 inhibitor. 2. The process according to claim 1 , wherein oxidation catalyst selected transition metal salts such as sodium molybdate claim 1 , sodium vanadate and sodium tungstate.3. The process according to claim 1 , wherein phase transfer catalyst selected from a group consisting of methyl-tri-n-octyl ammonium chloride claim 1 , methyl-tri-n-butyl ammonium chloride claim 1 , methyl-tri-n-butyl ammonium chloride claim 1 , benzethonium chloride claim 1 , and methyl benzethonium chloride.4. The process according to claim 1 , wherein the oxidation is carried out in presence of peroxide.5. The process according to claim 1 , wherein the process is conducted in biphasic system comprising of halogenated hydrocarbons and water.7. A process for preparation of 5-Chloro-3-(4-methylthio)phenyl-2-(2-methyl-5-pyridinyl)pyridine (IV) comprising reacting 1-(6-methyl-3-pyridinyl)-2[4-(methylthio)phenyl]ethanone (V) with 2-chloro-N claim 1 ,N-di methylamino trimethinium hexa fluoro phosphate (III) in presence of base followed by addition of alcohol and acid mixture claim 1 , adding an aqueous solution of ammonia followed by addition of ammonium salt claim 1 , heating claim 1 , to obtain 5-Chloro 3-(4-methylsulphonyl)phenyl-2-(2-methyl-5-pyridinyl)pyridine (IV).8. The process according to claim 7 , wherein claim 7 , base selected from sodium methoxide claim 7 , potassium methoxide claim 7 , potassium tert-butoxide claim 7 , ...

Подробнее
Номер записи: 46
26-09-2013 дата публикации

SEPARATING AGENT FOR PROTEIN PURIFICATION AND PROTEIN PURIFICATION METHOD

Номер: US20130253142A1
Автор: KOMIYA Katsuo, MASUMOTO Seiji, Nakamura Koji
Принадлежит: TOSOH CORPORATION

A novel separating agent for protein purification which not only can adsorb proteins in a sufficient amount for protein purification from a low concentration buffer but also can desorb the adsorbed protein easily just by altering the pH of the buffer and a simple and economical method for its production and a method for protein purification using it. 4. The separating agent for protein purification according to claim 1 , wherein the amount of the ligand on the support is at least 100 μmol/ml-support.5. The separating agent for protein purification according to claim 1 , wherein the support is made of a crosslinked polymer.9. The method for producing the separating agent for protein purification according to claim 6 , wherein the activator is carbonyldiimidazole.10. A method for protein purification claim 1 , which comprises dissolving a protein to be purified in a first buffer claim 1 , contacting the resulting protein solution with the separating agent for protein purification as defined in to allow the separating agent to adsorb the protein and then passing a second buffer having a different pH from the first buffer through the separating agent to elute the protein adsorbed on the separating agent. The present invention relates to a novel separating agent having a specific ligand for protein purification, a process for producing it and a protein purification method using it.In recent years, several techniques have been developed and/or optimized to effect separation and purification of target compounds from an aqueous mixture. Such separation and/purification techniques include, for example, ion exchange chromatography, hydrophobic interaction chromatography (HIC) (for example, Non-Patent Document 1), affinity chromatography and the like. The multiplicity of such chromatographic techniques reflects the difficulty in effecting separation and/or purification of target compounds while minimizing the complexity of the separation and/or purification procedure. Each of ...

Подробнее
Номер записи: 47
10-10-2013 дата публикации

ARYL SULFONAMIDES

Номер: US20130267492A1
Автор: Pennell Andrew, Ungashe Solomon, Wei Zheng, Wright John J.
Принадлежит: ChemoCentryx, Inc.

Compounds are provided that act as potent antagonists of the CCR9 receptor, and which have been further confirmed in animal testing for inflammation, one of the hallmark disease states for CCR9. The compounds are generally aryl sulfonamide derivatives and are useful in pharmaceutical compositions, methods for the treatment of CCR9-mediated diseases, and as controls in assays for the identification of CCR9 antagonists. 110-. (canceled)12. The compound of claim 11 , where L is —CO—.13. A composition comprising a pharmaceutically acceptable carrier and a compound of .15. The method of claim 14 , where the CCR9-mediated disease or condition is an inflammatory condition.16. The method of claim 14 , where the CCR9-mediated disease or condition is an immunoregulatory disorder.17. The method of claim 14 , where the CCR9-mediated condition or disease is inflammatory bowel disease.. The method of claim 14 , where the CCR9-mediated condition or disease is selected from the group consisting of an allergic disease claim 14 , psoriasis claim 14 , atopic dermatitis claim 14 , asthma claim 14 , fibrotic diseases and graft rejection.19. The method of claim 14 , where the CCR9-mediated condition or disease is selected from the group consisting of immune mediated food allergies and autoimmune diseases.20. The method of claim 19 , where the CCR9-mediated condition or disease is Celiac disease or rheumatoid arthritis.21. The method of claim 14 , where the administering is oral claim 14 , parenteral claim 14 , rectal claim 14 , transdermal claim 14 , sublingual claim 14 , nasal or topical.22. The method of claim 14 , where the compound is administered in combination with an anti-inflammatory or analgesic agent.23. The method of claim 14 , where the CCR9-mediated disease or condition is leukemia or a solid tumor.24. The method of claim 14 , where the CCR9-mediated disease or condition is thymoma or a thymic carcinoma.25. The method of claim 23 , where the CCR9-mediated disease or ...

Подробнее
Номер записи: 48
10-10-2013 дата публикации

Ampk-activating heterocyclic compounds and methods for using the same

Номер: US20130267702A1
Автор: Dane Goff, David Carroll, Donald Payan, Rajinder Singh, Simon Shaw, Yasumichi Hitoshi
Принадлежит: Rigel Pharmaceuticals Inc

Disclosed are substituted pyridine compounds as well as pharmaceutical compositions and methods of use. One embodiment is a compound having the structure wherein E, J, T, the ring system denoted by “B”, T, R 3 , R 4 , w and x are as described herein. In certain embodiments, a compound disclosed herein activates the AMPK pathway, and can be used to treat metabolism-related disorders and conditions.

Подробнее
Номер записи: 49
10-10-2013 дата публикации

N ortho acyl substituted nitrogen-containing heterocyclic compound and process for preparing aminal iron (ii) complexes thereof

Номер: US20130267708A1
Автор: Chunhong Wu, Haiying Zhang, Hongfei Wu, Huaijie Wang, Jilong Wang, Jun Liu, Lan Zhao, Mingfang Zheng, Qi Yanping, Tonglin Li, Weizhen Li, Wingjun Xie, YU Zhou, Zhiguang Jia
Принадлежит: China Petroleum and Chemical Corp, Sinopec Beijing Research Institute of Chemical Industry

Provided are a process for preparing an N ortho acyl substituted nitrogen-containing heterocyclic compound and an aminal iron (II) complex thereof, and the use of the complexes obtained by the process in an olefin oligomerization catalyst. The N ortho acyl substituted nitrogen-containing heterocyclic compound in the present invention is for example 2-acyl-1,10-phenanthroline or 2,6-diacetyl pyridine as shown in formula b, and the N ortho acyl substituted nitrogen-containing heterocyclic compound in the present invention is produced by a reaction of a precursor thereof in a substituted or unsubstituted nitrobenzene. Preferably the precursor shown in formula I in the present invention is produced by 1,10-phenanthroline reacting with trialkyl aluminum, or a halogenoalkyl aluminum R n AlX m , or a substituted or unsubstituted benzyl lithium 2 Li, followed by hydrolysis. The preparation method provided in the present invention has a few synthetic steps, an easy process, a low toxic effect, and reduces the preparation costs of the catalyst, and has a promising outlook in the industrial application.

Подробнее
Номер записи: 50
17-10-2013 дата публикации

FLUORENE COMPOUND AND PHARMACEUTICAL USE THEREOF

Номер: US20130274240A1
Автор: Ito Hirotsugu, Kobayashi Satoru, Morita Toru, Motomura Takahisa, Nagamori Hironobu, Shinkai Hisashi, Suzawa Koichi
Принадлежит:

The present invention provides an agent for the prophylactic or treatment of diabetes, diabetic complications, insulin resistance syndrome, metabolic syndrome, hyperglycemia, dyslipidemia, atherosclerosis, cardiac failure, cardiomyopathy, myocardial ischemia, brain ischemia, cerebral apoplexy, pulmonary hypertension, hyperlactacidemia, mitochondrial disease, mitochondrial encephalomyopathy or cancer, namely, a PDHK inhibitor and the like. A compound represented by the following formula [I] or a pharmaceutically acceptable salt thereof, or a solvate thereof: 217.-. (canceled)18. A pharmaceutical composition comprising a compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , or a solvate thereof claim 1 , and a pharmaceutically acceptable carrier.1923.-. (canceled)24. A method of inhibiting PDHK in a mammal claim 1 , comprising administering a pharmaceutically effective amount of a compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , or a solvate thereof to the mammal.25. A method of inhibiting PDHK2 in a mammal claim 1 , comprising administering a pharmaceutically effective amount of a compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , or a solvate thereof to the mammal.26. A method of decreasing the blood glucose level in a mammal claim 1 , comprising administering a pharmaceutically effective amount of a compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , or a solvate thereof to the mammal.27. A method of decreasing lactate level in a mammal claim 1 , comprising administering a pharmaceutically effective amount of a compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , or a solvate thereof to the mammal.28. A method for the treatment or prophylaxis of diabetes claim 1 , diabetic complications claim 1 , insulin resistance syndrome claim 1 , metabolic syndrome claim 1 , hyperglycemia claim 1 , dyslipidemia claim 1 , atherosclerosis claim 1 , ...

Подробнее
Номер записи: 51
24-10-2013 дата публикации

Compounds for the treatment of metabolic disorders

Номер: US20130281705A1
Автор: Shalini Sharma
Принадлежит: Wellstat Therapeutics Corp

Compounds useful for the treatment of various metabolic disorders, such as insulin resistance syndrome, diabetes, hyperlipidemia, fatty liver disease, cachexia, obesity, atherosclerosis and arteriosclerosis, are disclosed.

Подробнее
Номер записи: 52
31-10-2013 дата публикации

4-(p-QUINONYL)-2-HYDROXYBUTANAMIDE DERIVATIVES FOR TREATMENT OF MITOCHONDRIAL DISEASES

Номер: US20130289034A1
Автор: Kieron E. Wesson, Orion D. Jankowski, Paul Mollard, William D. Shrader
Принадлежит: Edison Phamaceuticals Inc

Methods of treating or suppressing mitochondrial diseases, such as Friedreich's ataxia (FRDA), Leber's Hereditary Optic Neuropathy (LHON), mitochondrial myopathy, encephalopathy, lactacidosis, and stroke (MELAS), Kearns-Sayre Syndrome (KSS), are disclosed, as well as compounds useful in the methods of the invention, such as 4-(p-quinolyl)-2-hydroxybutanamide derivatives. Methods and compounds useful in treating other disorders such as amyotrophic lateral sclerosis (ALS), Huntington's disease, Parkinson's disease, and pervasive developmental disorders such as autism are also disclosed. Energy biomarkers useful in assessing the metabolic state of a subject and the efficacy of treatment are also disclosed. Methods of modulating, normalizing, or enhancing energy biomarkers, as well as compounds useful for such methods, are also disclosed.

Подробнее
Номер записи: 53
07-11-2013 дата публикации

Heterocyclic ring compound

Номер: US20130296276A2
Автор: Kazuaki Takami, Nobuyuki Takakura, Nozomu Sakai, Osamu Ujikawa
Принадлежит: Takeda Pharmaceutical Co Ltd

The present invention provides a compound having a muscle cell or adipocyte differentiation regulating action, useful for the prophylaxis or treatment of diseases such as diabetes, obesity, dyslipidemia and the like, and the like, and having superior efficacy. The present invention provides a compound represented by the formula: wherein each symbol is as defined in the description, or a salt thereof.

Подробнее
Номер записи: 54
07-11-2013 дата публикации

System for Controlling the Reactivity of Boronic Acids

Номер: US20130296573A1
Автор: Burke Martin D., Gillis Eric P., Gray Kaitlyn C., Knapp David M., Lee Suk Joong
Принадлежит: The Board of Trustees of the University of Illinois

A protected organoboronic acid includes a boron having an sphybridization, a conformationally rigid protecting group bonded to the boron, and an organic group bonded to the boron through a boron-carbon bond. A method of performing a chemical reaction includes contacting a protected organoboronic acid with a reagent, the protected organoboronic acid including a boron having an sphybridization, a conformationally rigid protecting group bonded to the boron, and an organic group bonded to the boron through a boron-carbon bond. The organic group is chemically transformed, and the boron is not chemically transformed.

Подробнее
Номер записи: 55
14-11-2013 дата публикации

Pyridine Compounds and the Uses Thereof

Номер: US20130303526A1
Автор: Bin Shao, Chiyou NI, Jiangchao Yao, Jianming Yu, Laykea Tafesse, Xiaoming Zhou
Принадлежит: Purdue Pharma LP

The invention relates to substituted pyridine compounds of Formula (I) and the pharmaceutically acceptable salts, prodrugs, and solvates thereof, wherein R 1a , A 1 , A 2 , E, G, Z 1 , and Z 2 are defined as set forth in the specification. The invention is also directed to the use of compounds of Formula I to treat a disorder responsive to the blockade of sodium channels. Compounds of the present invention are especially useful for treating pain.

Подробнее
Номер записи: 56
14-11-2013 дата публикации

Novel biaromatic compounds that modulate ppary type receptors and cosmetic/pharmaceutical compositions comprised thereof

Номер: US20130303549A1
Автор: Corinne Millois Barbuis, Jean-Guy Boiteau, Laurence Clary
Принадлежит: Galderma Research and Development SNC

Novel biaromatic compounds having the general formula (I): and cosmetic/pharmaceutical compositions comprised thereof are useful in human or veterinary medicine (in dermatology and also in the fields of cardiovascular diseases, of immune diseases and/of diseases related to the metabolism of lipids), or, alternatively, in cosmetic compositions.

Подробнее
Номер записи: 57
14-11-2013 дата публикации

Enzyme inhibitors

Номер: US20130303576A1
Автор: Alastair David Graham Donald, Andrew James Belfield, Carl Leslie North, David Festus Charles Moffat, Stewart Andrew Wayne Jones
Принадлежит: Chroma Therapeutics Ltd

Compounds of formula (I), inhibit HDAC activity: wherein A, B and D independently represent ═CH— or ═N—; W is —CH═CH—Or —CH 2 CH 2 —; R 1 is a carboxylic acid group (—COOH), or an ester group which is hydrolysable by one or more intracellular carboxylesterase enzymes to a carboxylic acid group; R2 and R3 are selected from the side chains of a natural or non-natural alpha amino acid, provided that neither R 2 nor R 3 is hydrogen, or R 2 and R 3 , taken together with the carbon to which they are attached, form a 3-6 membered saturated cycloalkyl or heterocyclyl ring; Y is a bond, —C(═O)—, —S(═O) 2 —, —C(═O)O—, —C(═O)NR′—, —C(═S)—NR′, —C(═NH)NR′ or —S(═O) 2 NR— wherein R′ is hydrogen or optionally substituted C 1 -C 6 alkyl; L 1 is a divalent radical of formula -(Alk 1 ) m (Q) n (Alk 2 ) p - wherein m, n, p, Q. Alk 1 and Alk 2 are as defined in the claims; X 1 represents a bond; —C(═O); or —S(═O) 2 —; —NR 4 C(═O)—, —C(═O)NR 4 —, —NR 4 C(═O)NR 5 —, —NR 4 S(═O) 2 —, or —S(═O) 2 NR 4 — wherein R 4 and R 5 are independently hydrogen or optionally substituted C 1 -C 6 alkyl; and z is 0 or 1.

Подробнее
Номер записи: 58
21-11-2013 дата публикации

4-(4-PYRIDINYL)-BENZAMIDES AND THEIR USE AS ROCK ACTIVITY MODULATORS

Номер: US20130310378A1
Автор: Bonafoux Dominique, Hobson Adrian Donald, Hornberger Wilfried, Jarvis Michael F., Jr. Steven L., Keddy Ryan, Mack Helmut, Muller Bernhard K., Sauer Daryl, Swann, Teusch Nicole, Vasudevan Anil
Принадлежит:

The present invention relates to novel 4-(4-pyridyl)-benzamides of the formula (I). The compounds I possess valuable therapeutic properties and are suitable, in particular, for treating diseases that respond to modulation of Rho kinases (ROCKs). Rand Rare, independently of each other, hydrogen, hydroxy, cyano, C-C-alkyl, C-C-haloalkyl, C-C-alkoxy or C-C-haloalkoxy; R, R, Rand Rare, independently of each other, hydrogen, hydroxy, halogen, cyano, C-C-alkyl, C-C-haloalkyl, C-C-alkoxy, C-C-haloalkoxy, amino, C-C-alkylamino or di-(C-C-alkyl)-amino; Ris hydrogen, C-C-alkyl, C-C-haloalkyl, aryl or aryl-C-C-alkyl; Ris a group of the formula —X—W, where X is a single bond, C-C-alkylene or C-C-alkylene-O—, where the alkylene group in the three last-mentioned radicals may be linear or branched and may be partly or fully halogenated and/or may be substituted by a hydroxyl group and/or may be interrupted by an oxygen atom; and W is a cyclic radical selected from phenyl and a 5- or 6-membered saturated, partly unsaturated or aromatic heterocyclic ring which contains as ring members 1, 2 or 3 heteroatoms selected from O, S and N and optionally 1 or 2 carbonyl groups; Ris a group of the formula —Y—Z, where Z is hydrogen, halogen, OR, NRR, S(O)—R, phenyl which may carry 1, 2, 3 or 4 substituents Ror a 5- or 6-membered saturated, partly unsaturated or aromatic heterocyclic ring; and Y is linear or branched CC-alkylene which may be partly or fully halogenated and/or may be substituted by a hydroxyl group and/or a phenyl ring; or, in case Z is phenyl or the 5- or 6-membered heterocyclic ring as defined above, Y can also be a single bond. 2. The compound or salt as claimed in claim 1 , wherein Rand Rare claim 1 , independently of each other claim 1 , hydrogen claim 1 , hydroxy claim 1 , cyano claim 1 , C-C-alkyl claim 1 , C-C-haloalkyl claim 1 , C-C-alkoxy or C-C-haloalkoxy.3. The compound or salt as claimed in claim 1 , wherein Rand Rare hydrogen claim 1 , C-C-alkyl claim 1 , fluorine ...

Подробнее
Номер записи: 59
21-11-2013 дата публикации

Processes and Intermediates for Preparing Fused Heterocyclic Kinase Inhibitors

Номер: US20130310564A1
Автор: Claridge Stephen William, Granger Marie-Claude, Isakovic Ljubomir, Mannion Michael, Raeppel Franck, Vaisburg Arkadii, Zhan Lijie
Принадлежит: METHYLGENE INC.

This invention relates to intermediates for manufacturing fused heterocyclic-type kinase inhibitor compounds, such as thienopyridine-based compounds, particularly at an industrial level. 1. Field of the InventionThis invention relates to processes and intermediates for manufacturing fused heterocyclic-type compounds, such as thienopyridine-based kinase inhibitor compounds, and to processes and intermediates for preparing intermediates that are useful in the manufacture of fused heterocyclic-type compounds, such as thienopyridine-based kinase inhibitor compounds, particularly at an industrial level. Fused heterocyclic-type compounds have been found to be useful to inhibit protein tyrosine kinase activity. In particular, fused heterocyclic-type compounds, such as thienopyridine-based compounds, have been found useful to inhibit the protein tyrosine kinase activity of growth factor receptors, resulting in the inhibition of receptor signaling, for example, the inhibition of VEGF receptor signaling and HGF receptor signaling. Fused heterocyclic-type compounds have been found to be useful in the treatment of cancer by inhibiting protein tyrosine kinase activity. The pharmaceutical compositions that comprise these compounds are also useful in the treatment of diseases, other than cancer, which are associated with signal transduction pathways operating through growth factor and anti-angiogenesis receptors such as c-Met.2. Summary of the Related ArtTyrosine kinases may be classified as growth factor receptor (e.g. EGFR, PDGFR, FGFR and erbB2) or non-receptor (e.g. c-src and bcr-abl) kinases. The receptor type tyrosine kinases make up about 20 different subfamilies. The non-receptor type tyrosine kinases make up numerous subfamilies. These tyrosine kinases have diverse biological activity. Receptor tyrosine kinases are large enzymes that span the cell membrane and possess an extracellular binding domain for growth factors, a transmembrane domain, and an intracellular portion ...

Подробнее
Номер записи: 60
05-12-2013 дата публикации

PROCESSES AND REAGENTS FOR MAKING DIARYLIODONIUM SALTS

Номер: US20130324718A1
Автор: DiMagno Stephen
Принадлежит:

This invention relates to processes and reagents for making diaryliodonium salts, which are useful for the preparation of fluorinated and radiofluorinated aromatic compounds. 2. The process of claim 1 , wherein the process is carried out in the absence of added acid.3. The process of claim 1 , wherein the process utilizes (1-chloromethyl-4-fluoro-1 claim 1 ,4-diazoniabicyclo[2.2.2]octane)bis(tetrafluoroborate).4. The process of claim 1 , wherein the process utilizes (1-fluoro-4-methyl-1 claim 1 ,4-diazoniabicyclo[2.2.2]octane)bis(tetrafluoroborate).5. The process of claim 1 , wherein the process utilizes N-fluoro-2 claim 1 ,3 claim 1 ,4 claim 1 ,5 claim 1 ,6-pentachloropyridinium tetrafluoroborate.6. The process of claim 1 , wherein the process utilizes less than 2 equivalents of (1-chloromethyl-4-fluoro-1 claim 1 ,4-diazoniabicyclo[2.2.2]octane)bis(tetrafluoroborate) claim 1 , (1-fluoro-4-methyl-1 claim 1 ,4-diazoniabicyclo[2.2.2]octane)bis(tetrafluoroborate) claim 1 , or optionally substituted N-fluoropyridinium tetrafluoroborate for 1 equivalent of the compound of Formula II.7. The process of claim 1 , wherein the process utilizes less than 1.5 equivalents of (1-chloromethyl-4-fluoro-1 claim 1 ,4-diazoniabicyclo[2.2.2]octane)bis(tetrafluoroborate) claim 1 , (1-fluoro-4-methyl-1 claim 1 ,4-diazoniabicyclo[2.2.2]octane)bis(tetrafluoroborate) claim 1 , or optionally substituted N-fluoropyridinium tetrafluoroborate for 1 equivalent of the compound of Formula II.8. The process of claim 1 , wherein each X is claim 1 , independently claim 1 , a ligand that is a conjugate base of an acid HX claim 1 , wherein HX has a pKa of less than or equal to 5.9. The process of claim 1 , wherein each X is O(C═O)CH.10. The process of claim 1 , wherein the tetravalent silicon moiety is (R)Si—X claim 1 , wherein each Ris claim 1 , independently claim 1 , Calkyl or aryl.11. The process of claim 10 , wherein each Ris methyl.12. The process of claim 10 , wherein (R)Si—X is (CH)Si—X.13. The ...

Подробнее
Номер записи: 61
12-12-2013 дата публикации

SMALL MOLECULE INHIBITORS OF AGBL2

Номер: US20130331328A1
Автор: Byers Stephen W., Dakshanamurthy Sivanesan, Sahab Ziad
Принадлежит: GEORGETOWN UNIVERSITY

Small molecule inhibitors of AGBL2 are provided, as well as methods of using the inhibitors to treat or prevent cancer and neurologic disorders. 2. The compound of claim 1 , wherein Rand Rcombine to form a substituted or unsubstituted heterocycloalkyl.6. The compound of claim 5 , wherein Rand Rcombine to form a substituted or unsubstituted cycloalkyl.1110. A composition comprising a compound of any of - and a pharmaceutically acceptable carrier.13. The method of claim 12 , wherein Rand Rcombine to form a substituted or unsubstituted heterocycloalkyl.17. The method of claim 16 , wherein Rand Rcombine to form a substituted or unsubstituted cycloalkyl.2322. The method of any of - claims 1 , further comprising administering a second therapeutic agent to the subject.24. The method of claim 23 , wherein the second therapeutic agent is a chemotherapeutic agent.26. The method of claim 25 , wherein Rand Rcombine to form a substituted or unsubstituted heterocycloalkyl.30. The method of claim 29 , wherein Rand Rcombine to form a substituted or unsubstituted cycloalkyl.3635. The method of any of - claims 25 , further comprising administering a second therapeutic agent to the subject.37. The method of claim 36 , wherein the second therapeutic agent is an anti-depressant or an anxiolytic. This application claims priority to U.S. Provisional Application No. 61/443,069, filed Feb. 15, 2011, which is incorporated herein by reference in its entirety.The removal of the C-terminal tyrosine of α-tubulin to form detyrosinated α-tubulin is involved in several aspects of microtubule function, including kinesin interactions, spindle dynamics, mitosis, and neuronal specification. Microtubules containing large amounts of detyrosinated α-tubulin are more stable and resistant to depolymerization by destabilizing agents. Further, detyrosinated α-tubulin has been shown to be elevated in aggressive breast and prostate cancers.Provided herein are small molecule inhibitors of ATP/GTP binding protein ...

Подробнее
Номер записи: 62
12-12-2013 дата публикации

PIPERAZINYL AND PIPERIDINYL UREAS AS MODULATORS OF FATTY ACID AMIDE HYDROLASE

Номер: US20130331396A1
Автор: Apodaca Richard, Breitenbucher J. Guy, Pattabiraman Kanaka, Seierstad mark, Xiao Wei
Принадлежит: Janssen Pharmaceutica NV

Certain piperazinyl and piperidinyl urea compounds are useful as FAAH inhibitors. Such compounds may be used in pharmaceutical compositions and methods for the treatment of disease states, disorders, and conditions mediated by fatty acid amide hydrolase (FAAH) activity. Thus, the compounds may be administered to treat, e.g., anxiety, pain, inflammation, sleep disorders, eating disorders, or movement disorders (such as multiple sclerosis). 126.-. (canceled)28. A method according to claim 27 , wherein said compound is selected from the group consisting of:4-naphthalen-2-ylmethyl-piperazine-1-carboxylic acid phenylamide;4-quinolin-2-ylmethyl-piperazine-1-carboxylic acid phenylamide;4-benzo[b]thiophen-2-ylmethyl-piperazine-1-carboxylic acid phenylamide;4-(3,4-dibromo-benzyl)-piperazine-1-carboxylic acid phenylamide;4-(1-methyl-1H-indol-2-ylmethyl)-piperazine-1-carboxylic acid phenylamide;4-quinolin-3-ylmethyl-piperazine-1-carboxylic acid phenylamide;4-(4-iodo-benzyl)-piperazine-1-carboxylic acid phenylamide;4-(3-benzyloxy-benzyl)-piperazine-1-carboxylic acid phenylamide;4-(5-bromo-2-hydroxy-3-methoxy-benzyl)-piperazine-1-carboxylic acid phenylamide;4-(4-bromo-benzyl)-piperazine-1-carboxylic acid phenylamide;4-(3-phenoxy-benzyl)-piperazine-1-carboxylic acid phenylamide;4-(3-bromo-4-fluoro-benzyl)piperazine-1-carboxylic acid phenylamide;4-indan-5-ylmethyl-piperazine-1-carboxylic acid phenylamide;4-benzo[b]thiophen-3-ylmethyl-piperazine-1-carboxylic acid phenylamide;4-(4-isopropyl-benzyl)-piperazine-1-carboxylic acid phenylamide;4-(4-ethyl-benzyl)-piperazine-1-carboxylic acid phenylamide;4-(5-bromo-2-hydroxy-benzyl)-piperazine-1-carboxylic acid phenylamide;4-(2,3-dihydro-benzo[1,4]dioxin-6-ylmethyl)-piperazine-1-carboxylic acid phenylamide;4-(4-methoxy-benzyl)-piperazine-1-carboxylic acid phenylamide;4-(3-vinyl-benzyl)-piperazine-1-carboxylic acid phenylamide;4-(2,3-dihydro-benzofuran-5-ylmethyl)-piperazine-1-carboxylic acid phenylamide;4-(3-methoxy-benzyl)-piperazine-1- ...

Подробнее
Номер записи: 63
12-12-2013 дата публикации

ARYL UREA DERIVATIVES AS N-FORMYL PEPTIDE RECEPTOR LIKE-1 (FPRL-1) RECEPTOR MODULATORS

Номер: US20130331570A1
Автор: Beard Richard L., Donello John E., Duong Tien T., Garst Michael E., Viswanath Veena
Принадлежит: ALLERGAN, INC.

The present invention relates to novel aryl urea derivatives, processes for preparing them, pharmaceutical compositions containing them and their use as pharmaceuticals as modulators of the N-formyl peptide receptor like-1 (FPRL-1) receptor. 2. A compound according to claim 1 , wherein:{'sup': '8', 'Ris Br.'}3. A compound according to claim 1 , wherein:{'sup': '6', 'sub': 2', '6-10, 'Ris —CH—(C)aryl.'}4. A compound according to claim 1 , wherein:{'sup': '6', 'sub': '2', 'Ris —CH-heterocycle.'}5. A compound according to claim 1 , wherein:{'sup': '10', 'Ris OH.'}6. A compound according to claim 1 , wherein:{'sup': '10', 'sub': '2', 'Ris NH.'}7. A compound according to claim 1 , wherein:{'sup': '7', 'Ris H;'}{'sup': '8', 'Ris Br; and'}{'sup': '9', 'Ris H.'}8. A compound according to claim 1 , wherein the compound is selected from:(2S)-2-({[(4-Bromo-2-fluorophenyl)amino]carbonyl}amino)-3-phenylpropanoic acid;(2S)-2-({[(4-Bromo-2-methylphenyl)amino]carbonyl}amino)-3-phenylpropanoic acid;(2S)-2-({[(4-Bromo-2,6-difluorophenyl)amino]carbonyl}amino)-3-phenylpropanoic acid;(2S)-2-({[(4-Bromo-2,6-dimethylphenyl)amino]carbonyl}amino)-3-phenylpropanoic acid;(2R)-2-({[(4-Bromo-2-fluorophenyl)amino]carbonyl}amino)-3-phenylpropanoic acid;(2S)-2-[({[4-(methylthio)phenyl]amino}carbonyl)amino]-3-phenylpropanoic acid;(2R)-2-[({[4-(methylthio)phenyl]amino}carbonyl)amino]-3-phenylpropanoic acid;2-({[(4-bromophenyl)amino]carbonyl}amino)-3-pyridin-2-ylpropanoic acid;2-({[(4-bromo-2-fluorophenyl)amino]carbonyl}amino)-3-pyridin-2-ylpropanoic acid;2-({[(4-bromo-2-fluorophenyl)amino]carbonyl}amino)-3-(1H-indol-3-yl)propanoic acid; and(2S)-2-({[(4-bromophenyl)amino]carbonyl}amino)-3-phenylpropanamide. This application is a divisional application of U.S. Non-Provisional patent application Ser. No. 13/668,835, filed Nov. 5, 2012, which claims the benefit of U.S. Provisional Application Ser. No. 61/558,121, filed on Nov. 10, 2011, all of which are incorporated here by reference in their entirety. ...

Подробнее
Номер записи: 64
19-12-2013 дата публикации

Chemosensory Receptor Ligand-Based Therapies

Номер: US20130338095A1
Автор: Baron Alain D., Beeley Nigel R.A., Brown Martin R., Jones Christopher R.G.
Принадлежит: Elcelyx Therapeutics, Inc.

Provided herein are methods for treating conditions associated with a chemosensory receptor, including diabetes, obesity, and other metabolic diseases, disorders or conditions by administering a composition comprising a chemosensory receptor ligand. Also provided herein are chemosensory receptor ligand compositions and methods for the preparation thereof for use in the methods of the present invention. 193-. (canceled)120. A composition according to claim 94 , wherein the composition further releases at least some of the chemosensory receptor ligand in the stomach.121. A composition according to claim 94 , wherein one or more regions of the intestine are the duodenum claim 94 , jejunum claim 94 , ileum claim 94 , caecum claim 94 , colon and/or rectum.122. A composition according to claim 94 , wherein the composition releases at an onset of about 5 to about 45 minutes claim 94 , about 105 to about 135 minutes claim 94 , about 165 to about 195 minutes claim 94 , about 225 to about 255 minutes or a combination of times thereof following administration to a subject.123. A composition according to claim 94 , wherein the composition releases at an onset of about pH 5.0 claim 94 , about pH 5.5 claim 94 , about pH 6.0 claim 94 , about pH 6.5 claim 94 , about pH 7.0 claim 94 , or combination thereof following administration to a subject.124. A composition according to claim 94 , the composition further comprising a second chemosensory receptor ligand selected from the group consisting of a sweet receptor ligand claim 94 , a bitter receptor ligand claim 94 , an umami receptor ligand claim 94 , a fat receptor ligand claim 94 , a sour receptor ligand and a bile acid receptor ligand.125. A composition according to claim 124 , wherein the sweet receptor ligand is selected from the group consisting of sucralose claim 124 , aspartame claim 124 , Stevioside claim 124 , Rebaudioside A claim 124 , Rebaudioside B claim 124 , Rebaudioside C claim 124 , Rebaudioside D claim 124 , ...

Подробнее
Номер записи: 65
02-01-2014 дата публикации

B- and y -diketones and y -hydroxyketones as wnt/ b -catenin signaling pathway activators

Номер: US20140005228A1
Автор: Charlene F. Barroga, David Mark Wallace, John Hood, Sunil Kumar Kc
Принадлежит: Samumed LLC

The present invention discloses β-diketones, γ-diketones or γ-hydroxyketones or analogs thereof, that activate Wnt/β-catenin signaling and thus treat or prevent diseases related to signal transduction, such as osteoporosis and osteoarthropathy; osteogenesis imperfecta, bone defects, bone fractures, periodontal disease, otosclerosis, wound healing, craniofacial defects, oncolytic bone disease, traumatic brain injuries related to the differentiation and development of the central nervous system, comprising Parkinson's disease, strokes, ischemic cerebral disease, epilepsy, Alzheimer's disease, depression, bipolar disorder, schizophrenia; eye diseases such as age related macular degeneration, diabetic macular edema or retinitis pigmentosa and diseases related to differentiation and growth of stem cell, comprising hair loss, hematopoiesis related diseases and tissue regeneration related diseases.

Подробнее
Номер записи: 66
02-01-2014 дата публикации

p53-Mdm2 ANTAGONISTS

Номер: US20140005386A1
Автор: DOEMLING Alexander
Принадлежит:

Novel p53-Mdm2 antogonists that conform to Formula I or to Formula II: 2. The compound according to claim 1 , wherein Ris chlorine claim 1 , Ris hydrogen claim 1 , —C(O)R′ claim 1 , and —C(O)OR′ and Ris hydrogen.3. The compound according to claim 2 , wherein Ris —C(O)OR′.4. The compound according to claim 3 , wherein R′ is hydrogen or ethyl.5. The compound according to claim 2 , wherein Ris —C(O)R′.6. The compound according to claim 5 , wherein R′ is —NH—(C-C)alkylene-(C-C)heteroaryl.8. The compound according to claim 5 , wherein R′ is —(C-C)heterocycloalkylene-N(R″)(R′″).10. The compound according to claim 1 , wherein Ris indole.11. The compound according to claim 1 , wherein Ris benzyl.14. The compound according to claim 13 , wherein Ris benzyl and X is —(O) and Ris hydrogen.15. The compound according to claim 13 , wherein Ris —(C-C)alkyl.16. The compound according to claim 15 , wherein Ris methyl.17. The compound according to claim 13 , wherein Ris benzyl and X is —NH— and Ris —(C-C)alkyl.19. The compound according to claim 13 , wherein Ris isobutyl. This application claims the benefit of U.S. Provisional Application No. 61/381,038, filed Sep. 8, 2010, which is fully incorporated by reference.The protein-protein interaction (PPI) between the transcription factor p53 and its negative regulator Mdm2 is a major target in current cancer drug discovery. Disrupting the interaction between p53 and Mdm2 was shown to restore the wild type p53 activity and drive cancer cells selectively into apoptosis.Many investigations of small molecule p53-Mdm2 antagonists in different cancer cell lines and animal models support their usefulness as potential anticancer agents with a novel mode-of-action. While several classes of small molecule p53-Mdm2 antagonists have been described in the literature, only a few compounds are of sufficient potency and have been structurally characterized. See Czarna, A.; Beck, B.; Srivastava, S.; Popowicz, G. M.; Wolf, S.; Huang, Y.; Bista, M.; Holak, ...

Подробнее
Номер записи: 67
16-01-2014 дата публикации

Hedgehog antagonists having zinc binding moieties

Номер: US20140018368A1
Автор: Changgeng Qian, Haixiao Zhai, Xiong Cai
Принадлежит: Curis Inc, Genentech Inc

The present invention provides compounds which antagonize hedgehog signaling and inhibit HDAC activity. The compounds can be used in methods of treating proliferative diseases and disorders such as cancer.

Подробнее
Номер записи: 68
16-01-2014 дата публикации

Novel synthesis for thiazolidinedione compounds

Номер: US20140018542A1
Автор: James R. Zeller, Robert C. Gadwood, Scott D. Larsen, Steven P. Tanis, Timothy Parker
Принадлежит: Metabolic Solutions Development Co LLC

The present invention provides novel methods for synthesizing PPARγ sparing compounds, e.g., thiazolidinediones, that are useful for preventing and/or treating metabolic disorders such as diabetes, obesity, hypertension, and inflammatory diseases.

Подробнее
Номер записи: 69
23-01-2014 дата публикации

GONADOTROPIN-RELEASING HORMONE RECEPTOR ANTAGONISTS AND METHODS RELATING THERETO

Номер: US20140024665A1
Автор: Ashweek Neil, Beaton Graham, Chen Mi, Coon Timothy Richard, Ewing Todd, Jiang Wanlong, Lowe Richard, Moree Willy, Rowbottom Martin, Smith Nicole, Wade Warren, Zhao Liren, Zhu Yun-Fei
Принадлежит:

GnRH receptor antagonists are disclosed which have utility in the treatment of a variety of sex-hormone related conditions in both men and women. The compounds of this invention have the structure: 3. The compound of wherein A is pyridyl substituted with 0-4 R.4. The compound of wherein A is 2-pyridyl substituted with 0-4 R.5. The compound of wherein A is 3-pyridyl substituted with 0-4 R.6. The compound of wherein A is 3-pyridyl substituted with 0-4 R.79.-. (canceled)10. The compound of wherein Rand Rare H.11. The compound of wherein Ris —Calkyl-(R)or —O—Calkyl-(R) claim 1 , p is 1 claim 1 , and Ris H claim 1 , hydroxy or —COOR.12. The compound of wherein one of Ris —O—Calkyl-(R) claim 2 , p is 1 claim 2 , and Ris H claim 2 , hydroxy claim 2 , or —COOR.13. The compound of wherein one of Ris —Calkyl-(R) claim 1 , —Calkyl-O—Calkyl-(R)or —O—Calkyl-(R).1415.-. (canceled)16. The pharmaceutical composition comprising the compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , and a pharmaceutically acceptable carrier or diluent.17. The method for treating a sex-hormone related condition of a subject in need thereof claim 16 , comprising administering to the subject an effective amount of the pharmaceutical composition of .18. A method for treating a condition in a subject in need thereof claim 16 , wherein said condition is endometriosis claim 16 , uterine fibroids claim 16 , polycystic ovarian disease claim 16 , dysmenorrhea claim 16 , dyspareunia claim 16 , menorrhagia claim 16 , nonmenstrual pelvic pain claim 16 , pelvic tenderness claim 16 , induration claim 16 , general disorders of the menstrual cycle claim 16 , premature ovarian failure due to chemotherapy or early menopause claim 16 , hirsutism claim 16 , precocious puberty claim 16 , gonadal steroid-dependent neoplasia including cancers of the prostate claim 16 , breast and ovary claim 16 , gonadotroph pituitary adenomas claim 16 , adenomyosis claim 16 , sleep apnea claim 16 , irritable ...

Подробнее
Номер записи: 70
06-03-2014 дата публикации

Composition and Methods for Modulating a Kinase Cascade

Номер: US20140066445A1
Автор: Hangauer, JR. David G.
Принадлежит:

The invention relates to compounds and methods for modulating one or more components of a kinase cascade. The invention also relates to substantially pure compound 1 and substantially pure compound 1 salt (e.g., compound 1 hydrochloride salt and compound 1 benzenesulfonate salt). The invention further relates to methods of preparing substantially pure compound 1 and compound 1 salts. 2. The composition of claim 1 , further comprising a pharmaceutically acceptable carrier or excipient.3. A composition comprising a compound 1 salt having a purity greater than 98.0% as determined by HPLC.4. The composition of claim 3 , wherein the salt is benzenesulfonate salt.5. The composition of claim 3 , further comprising a pharmaceutically acceptable carrier or excipient.6. A method of modulating one or more components of a protein kinase signaling cascade in a subject claim 1 , comprising administering to the subject the composition of .7. The method of claim 6 , wherein the one or more components of the protein kinase signaling cascade are responsible for the manifestation of a disease or disorder selected from hyperproliferative disorders claim 6 , cancers claim 6 , pre-cancers claim 6 , osteoporosis claim 6 , cardiovascular disorders claim 6 , immune system dysfunction claim 6 , type II diabetes claim 6 , obesity claim 6 , hearing loss claim 6 , and transplant rejection.8. A method of modulating one or more components of a protein kinase signaling cascade claim 2 , in a subject claim 2 , comprising administering to the subject the composition of .9. The method of claim 8 , wherein the one or more components of the protein kinase signaling cascade are responsible for the manifestation of a disease or disorder selected from hyperproliferative disorders claim 8 , cancers claim 8 , pre-cancers claim 8 , osteoporosis claim 8 , cardiovascular disorders claim 8 , immune system dysfunction claim 8 , type II diabetes claim 8 , obesity claim 8 , hearing loss claim 8 , and transplant ...

Подробнее
Номер записи: 71
06-03-2014 дата публикации

Modified Amino Acids

Номер: US20140066598A1
Автор: Stafford Ryan, Thanos Christopher D., Yang Wenjin
Принадлежит: Sutro Biopharma, Inc.

Provided herein are modified amino acids comprising an azido group, polypeptides, antibodies and conjugates comprising the modified amino acids, and methods of producing the polypeptides, antibodies and conjugates comprising the modified amino acids. The polypeptides, antibodies and conjugates are useful in methods of treatment and prevention, methods of detection and methods of diagnosis. 2. The compound of claim 1 , wherein D is —Ar—W—.3. The compound of claim 1 , wherein D is —W—Y—C(O)—Y—W—.7. The compound of wherein:{'sub': 1', '1', '2', '2, 'D is —W—Y—C(O)—Y—W—; and'}{'sub': '1', 'each Yis independently —NH— or —O—.'}8. The compound of claim 1 , wherein:{'sub': 1', '1', '2', '2, 'D is —W—Y—C(O)—Y—W—;'}{'sub': '2', 'each Yis independently an N-linked or C-linked pyrrolidinylene; and'}{'sub': '2', 'each Wis a single bond.'}9. The compound of claim 1 , wherein:{'sub': 1', '1', '2', '2, 'D is —W—Y—C(O)—Y—W—;'}{'sub': '2', 'each Yis independently a single bond, —NH— or —O—; and'}{'sub': '2', 'each Wis lower alkylene.'}11. The compound of claim 1 , wherein each of Wand Wis independently C-Calkylene.15. A polypeptide comprising an amino acid residue corresponding to the compound of .16. A conjugate comprising the polypeptide of linked to a payload and optionally comprising a linking moiety between the polypeptide and the payload.17. An antibody comprising an amino acid residue corresponding to the compound of .18. A conjugate comprising the antibody of linked to a payload and optionally comprising a linking moiety between the antibody and the payload.19. An orthogonal tRNA aminoacylated with an amino acid residue corresponding to the compound of .20. A method of producing a polypeptide claim 19 , comprising contacting a polypeptide with the orthogonal tRNA of under conditions suitable for incorporating the amino acid residue into the polypeptide.21. The method of claim 20 , wherein the orthogonal tRNA base pairs with a codon that is not normally associated with an ...

Подробнее
Номер записи: 72
13-03-2014 дата публикации

FE(II) SEQUESTERING AGENTS AND USES THEREOF

Номер: US20140072517A1
Автор: Morrow Janet, Tsitovich Pavel
Принадлежит: The Research Foundation of State University of New

Compounds and uses of the compounds are provided. The compounds can be used as Fe(II) sequestering compounds. For example, these compounds can be used to sequester Fe(II) in cells, organs, vasculature, or tissues. Also, provided are compositions and methods of using the them for sequestering Fe(II) in an individual. The compounds can be used as MRI paraCEST contrast agents. 10) The compound of claim 1 , wherein the compound has an Fe(II) cation complexed to the compound.11) A composition comprising a compound of and a pharmaceutically acceptable carrier.12) A method to obtain an image of at least a portion of a cell claim 1 , organ claim 1 , vasculature claim 1 , or tissue comprising the steps of:{'claim-ref': {'@idref': 'CLM-00001', 'claim 1'}, 'contacting the cell, organ, vasculature, or tissue with a compound of , and'}imaging at least a portion of the cell, organ, vasculature, or tissue to obtain an image of the portion of the cell, organ, vasculture or tissue,wherein the image is obtained using magnetic resonance imaging.13) The method of claim 12 , wherein the cell claim 12 , organ claim 12 , vasculature claim 12 , or tissue is part of an individual.14) The method of claim 12 , wherein the image is obtained using Magnetic Resonance Imaging (MRI).15) The method of claim 12 , wherein the image is obtained using chemical exchange saturation transfer (CEST).16) The method of claim 12 , wherein the image is obtained using paramagnetic chemical exchange saturation transfer (paraCEST).17) The method of claim 12 , wherein the image is obtained using magnetic resonance spectroscopy imaging (MRSI).18) The method of claim 12 , wherein the image is obtained using thermometry.19) The method of claim 12 , wherein the image is obtained using pH mapping. This application claims priority to U.S. provisional patent application No. 61/484,873, filed May 11, 2011, U.S. provisional patent application No. 61/583,039, filed Jan. 4, 2012, and U.S. provisional patent application No. ...

Подробнее
Номер записи: 73
20-03-2014 дата публикации

Inhibitors of Histone Deacetylase

Номер: US20140080800A1
Автор: Haggarty Stephen, Holson Edward, Tsai Li-Huei, Wagner Florence Fevrier, Weiwer Michel, ZHANG YAN-LING
Принадлежит:

The present invention relates to compounds of formula (I): 5. The compound of or a pharmaceutically acceptable salt claim 4 , hydrate claim 4 , solvate claim 4 , or prodrug thereof claim 4 , wherein Ris selected from phenyl claim 4 , 2-pyridinyl claim 4 , 3-pyridinyl claim 4 , 4-pyridinyl claim 4 , 2-pyrimidinyl claim 4 , 4-pyrimidinyl claim 4 , 5-pyrimidinyl claim 4 , 2-pyrazinyl claim 4 , oxazolyl claim 4 , thiazolyl claim 4 , and isoxazolyl.12. A pharmaceutical composition comprising an effective amount of a compound of or a pharmaceutically acceptable salt claim 1 , hydrate claim 1 , solvate claim 1 , or prodrug thereof and a pharmaceutical carrier claim 1 , diluent claim 1 , or excipient.13. A method of treating claim 1 , alleviating claim 1 , and/or preventing a condition wherein said condition is associated with histone deacetylase activity in a subject comprising administering to the subject in need thereof an effective amount of a compound of or a pharmaceutically acceptable salt claim 1 , hydrate claim 1 , solvate or prodrug thereof.14. The method of claim 13 , wherein the condition is selected from a neurological disorder claim 13 , memory loss or impairment claim 13 , cognitive function disorder or impairment claim 13 , extinction learning disorder claim 13 , fungal disease or infection claim 13 , inflammatory disease claim 13 , hematological disease claim 13 , and neoplastic disease.15. The method of claim 14 , wherein the condition is selected from:a cognitive function disorder or impairment associated with Alzheimer's disease, Huntington's disease, seizure induced memory loss, schizophrenia, Rubinstein Taybi syndrome, Rett Syndrome, Fragile X, Lewy body dementia, vascular dementia, ADHD, dyslexia, bipolar disorder and social, cognitive and learning disorders associated with autism, traumatic head injury, or attention deficit disorder, anxiety disorder, conditioned fear response, panic disorder, obsessive compulsive disorder, posttraumatic stress ...

Подробнее
Номер записи: 74
20-03-2014 дата публикации

GPBP inhibition using Q2 peptidomimetics

Номер: US20140080852A1
Автор: Blasco Raúl, Fustero Santos, Pérez-Payá Enrique, Revert Fernando, Revert-Ros Francisco, Sanz-Cervera Juan F, Saus Juan
Принадлежит: FIBROSTATIN, S.L.

Disclosed are compounds of formula: 3. A compound according to claim 1 , wherein{'sub': 1', '1', '6', '1', '6', '1', '6', '1', '6, 'Ris hydrogen, halogen, hydroxy, C-Calkyl, halo(C-Calkyl), C-Calkoxy, or halo(C-Calkoxy);'}{'sub': 2', '1', '6', '1', '6', '1', '6', '1', '6', '1', '6', '0', '6', '1', '6', '1', '6', '1', '6', '1', '6, 'Ris C-Calkyl, halo(C-Calkyl), hydroxy(C-Calkyl), (C-Calkoxy)C-Calkyl, formyl(C-Calkyl), amino(C-Calkyl), sulfanyl(C-Calkyl), or (C-Calkyl)sulfanyl(C-Calkyl);'}{'sub': 3', '1', '6', '2', '1-5', '2', '1-5', '1', '6', '2', '1-5', '2', '2', '1-5', '1', '6', '2', '1-5', '1', '6', '2', '1', '6, 'Ris C-Calkyl, —(CH)—C(O)OH, —(CH)—C(O)(C-Calkoxy), —(CH)—C(O)NH, —(CH)—C(O)NH(C-Calkyl), —(CH)—C(O)N(C-Calkyl), —CH═CH—C(O)OH, or —CH═CH—C(O)(C-Calkoxy); and'}{'sub': 4', '1', '6', '1', '6', '1', '6', '2', '1-5', '2', '1-5', '1', '6', '2', '1-5', '2', '2', '1-5', '1', '6', '2', '1-5', '1', '6', '2', '1', '6', '2', '1-5', '2', '1-5', '1', '6, 'Ris hydroxy, halogen, C-Calkyl, C-Calkoxy, halo(C-Calkoxy), benzyloxy, —(CH)—C(O)OH, —(CH)—C(O)(C-Calkoxy), —(CH)—C(O)NH, —(CH)—C(O)NH(C-Calkyl), —(CH)—C(O)N(C-Calkyl), —CH═CH—C(O)OH, —CH═CH—C(O)(C-Calkoxy), —O(CH)—C(O)OH, or —O(CH)—C(O)(C-Calkoxy).'}4. (canceled)5. (canceled)6. A compound according to claim 1 , wherein Ris hydrogen.7. A compound according to claim 1 , wherein{'sub': 2', '1', '6', '1', '6', '1', '6', '0', '6', '1', '6', '1', '6, 'Ris C-Calkyl, halo(C-Calkyl), hydroxy(C-Calkyl), formyl(C-Calkyl), amino(C-Calkyl), or sulfanyl(C-Calkyl).'}8. A compound according to claim 7 , wherein Ris C-Calkyl claim 7 , halo(C-Calkyl) claim 7 , or hydroxy(C-Calkyl).9. A compound according to claim 1 , wherein{'sub': 3', '1', '6', '2', '1-5', '2', '1-5', '1', '6', '1', '6, 'Ris C-Calkyl, —(CH)—C(O)OH, —(CH)—C(O)(C-Calkoxy), —CH═CH—C(O)OH, or —CH═CH—C(O)(C-Calkoxy).'}10. A compound according to claim 9 , wherein Ris —(CH)—C(O)OH claim 9 , or —(CH)—C(O)(C-Calkoxy).11. A compound according to claim 1 , wherein{'sub': 4 ...

Подробнее
Номер записи: 75
27-03-2014 дата публикации

PHENICOL ANTIBACTERIAL AGENTS

Номер: US20140088046A1
Автор: Billen Denis, Curtis Michael, Ewin Richard Andrew, Goodwin Richard M., Johnson Paul D., Johnson Timothy Allan, Kyne Graham M., Maddux Todd M., Sheehan Susan Mary Kult, Vairagoundar Rajendran
Принадлежит: Zoetis LLC

The present invention provides novel phenicol derivatives, their use for the treatment of infections in mammals, pharmaceutical composition containing these novel compounds, and methods for the preparation of these compounds. 2. A compound of wherein Het moiety is a 5- or 6-membered cyclic ring system having from 1 to 3 hetero atoms selected from N claim 1 , O claim 1 , and S claim 1 , optionally substituted with R.3. A compound of wherein Het is pyridinyl claim 2 , oxo-pyridinyl claim 2 , isoxazolyl claim 2 , thiazolyl claim 2 , thiadiazolyl claim 2 , thiophenyl claim 2 , oxazolyl claim 2 , pyrazolyl claim 2 , or thiadiazolyl.4. A compound of wherein Het is pyridinyl claim 3 , oxo-pyridinyl claim 3 , isoxazolyl claim 3 , thiazolyl claim 3 , or thiophenyl.5. A compound of wherein n is 0 or 1.6. A compound of wherein W is H claim 1 , —PO(OH) claim 1 , or —CHOPO(OH).7. A compound of selected from the group consisting of:3-[5-(4-{(1R,2S)-2-[(difluoroacetyl)amino]-3-fluoro-1-hydroxypropyl}phenyl)pyridin-2-yl]oxetan-3-yl dihydrogen phosphate;(1R,2S)-2-[(difluoroacetyl)amino]-3-fluoro-1-{4-[6-(3-hydroxyoxetan-3-yl)pyridin-3-yl]phenyl}propyl dihydrogen phosphate; and(1R,2S)-1-(4-(6-(cyanomethyl)pyridin-3-yl)phenyl)-2-(2,2-difluoroacetamido)-3-fluoropropyl dihydrogen phosphate.8. A compound of wherein W is H.9. A compound of wherein Rand Rtaken together with the carbon to which they are attached form a 4 to 6 membered heterocyclic ring moiety optionally having 1-2 hetero atoms selected from the group consisting of N claim 1 , NR claim 1 , S claim 1 , SO claim 1 , SO claim 1 , and O claim 1 , wherein the heteroatom or the heterocyclic is optionally substituted with R.10. A compound of wherein Rand Rtaken together with the carbon to which they are attached form an oxetanyl or an azetidinyl.11. A compound of wherein Ris —OW claim 1 , -Halo claim 1 , —CN claim 1 , or SOR; wherein W is hydrogen or —PO(OH); and Ris —C-Calkyl.12. A compound of wherein X claim 1 , Y and Z are ...

Подробнее
Номер записи: 76
27-03-2014 дата публикации

ENDOPARASITE CONTROL AGENT

Номер: US20140088157A1
Автор: Kita Kiyoshi, Suwa Akiyuki
Принадлежит:

Provided are an endoparasite control agent comprising a carboxamide derivative represented by the general formula (I): 2. The endoparasite control agent according to claim 1 ,{'sub': 1', '8', '1', '6', '3', '6', '1', '8', '1', '6', '3', '6', '2', '1', '6', '3', '6', '1', '6', '1', '6, 'wherein A represents a (C-C) alkylene group optionally substituted by a halogen atom, a (C-C) alkyl group and/or a (C-C) cycloalkyl group; or a (C-C) alkylene group which is optionally substituted by a halogen atom, a (C-C) alkyl group and/or a (C-C) cycloalkyl group and is modified by incorporation, into the carbon chain, of at least one heteroatom selected from an oxygen atom, a sulfur atom, —SO—, —SO— and —N(R)— (wherein R represents a hydrogen atom, a (C-C) alkyl group, a (C-C) cycloalkyl group, a (C-C) alkylcarbonyl group or a (C-C) alkoxycarbonyl group).'}3. The endoparasite control agent according to claim 1 ,{'sub': 1', '8', '1', '6', '3', '6', '1', '6', '3', '6', '3', '6', '2', '1', '6', '3', '6', '1', '6', '1', '6', '1', '6', '3', '6', '3', '6, 'sup': 1', '2', '3', '4', '1', '2', '3', '4', '1', '2', '3', '4', '1', '2', '3', '4', '5', '6', '1', '2', '3', '4', '5', '6', '1', '2', '3', '4', '5', '6, 'wherein A represents a (C-C) alkylene group optionally substituted by a (C-C) alkyl group and/or a (C-C) cycloalkyl group; —CR(R)—CR(R)-Q- (wherein R, R, Rand Rmay be the same or different from each other, and represent a hydrogen atom, a (C-C) alkyl group or a (C-C) cycloalkyl group, or R, R, Rand Rmay join together in any combination to form a (C-C) cycloalkane, and Q represents an oxygen atom, a sulfur atom, —SO—, —SO— or —N(R)— (wherein R represents a hydrogen atom, a (C-C) alkyl group, a (C-C) cycloalkyl group, a (C-C) alkylcarbonyl group or a (C-C) alkoxycarbonyl group)); or —CR(R)—CR(R)—CR(R)-Q- (wherein R, R, R, Rand Q are as defined above, and Rand Rmay be the same or different from each other, and represent a hydrogen atom, a (C-C) alkyl group or a (C-C) cycloalkyl group, ...

Подробнее
Номер записи: 77
03-04-2014 дата публикации

METHODS OF LOWERING PROPROTEIN CONVERSATE SUBTILISIN/KEXIN TYPE 9 (PCSK9)

Номер: US20140093513A1
Автор: Jirousek Michael R., Milne Jill C., Vu Chi B.
Принадлежит: CATABASIS PHARMACEUTICALS, INC.

The invention relates to new methods of modulating cholesterol by inhibiting proprotein convertase subtilisin/kexin type 9 (PCSK9) with fatty acid derivatives; and new methods for treating or preventing a metabolic disease comprising the administration of an effective amount of a fatty acid derivative. The present invention is also directed to fatty acid bioative derivatives and their use in the treatment of metabolic diseases. 1. A method for treating a metabolic disease comprising inhibiting the production of or lowering serum levels of the proprotein convertase subtilisin/kexin type 9 (PCSK9) by administering to a patient in need thereof an effective amount of a fatty acid bioactive derivative.2. The method of claim 1 , wherein the metabolic disease is selected from hypertriglyceridemia claim 1 , severe hypertriglyceridemia claim 1 , hypercholesterolemia claim 1 , familial hypercholesterolemia claim 1 , elevated cholesterol caused by a genetic condition claim 1 , fatty liver disease claim 1 , nonalcoholic fatty liver disease (NFLD) claim 1 , nonalcoholic steatohepatitis (NASH) claim 1 , dyslipidemia claim 1 , mixed dyslipidemia claim 1 , Type I hyperlipoproteinemia (which can include 3 subtypes: Type Ia claim 1 , also called Buerger-Gruetz syndrome or familial hyperchylomicronemia; Type Ib claim 1 , also called familial apoprotein CII deficiency claim 1 , and Type Ic) claim 1 , Type V hyperlipoproteinemia claim 1 , atherosclerosis claim 1 , coronary heart disease claim 1 , Type 2 diabetes claim 1 , diabetic nephropathy claim 1 , diabetic neuropathy claim 1 , diabetic retinopathy claim 1 , metabolic syndrome claim 1 , or cardiovascular disease.3. The method of claim 2 , wherein the method further comprises administering another therapeutic agent selected from the group consisting of atorvastatin claim 2 , cerivastatin claim 2 , fluvastatin claim 2 , lovastatin claim 2 , pitavastatin claim 2 , pravastatin claim 2 , rosuvastatin claim 2 , simvastatin claim 2 , ...

Подробнее
Номер записи: 78
03-04-2014 дата публикации

Compounds as S-Nitrosoglutathione Reductase Inhibitors

Номер: US20140094465A1
Автор: Qiu Jian, Stout Adam, Sun Xicheng
Принадлежит:

The present invention is directed to compounds useful as S-nitrosoglutathione reductase (GSNOR) inhibitors, pharmaceutical compositions comprising such compounds, and methods of making and using the same. 1. What is claimed is: {'br': None, 'sub': 1', '2, 'HO-Cy-linker-Cy-acidic moiety\u2003\u2003Formula 1'}, 'A method of inhibiting GSNOR in a patient in need thereof by administering an effective amount of a compound of Formula 1 or a pharmaceutically acceptable salt thereofwherein{'sub': '1', 'Cyis selected from the group consisting of substituted and unsubstituted monocyclic aryl, substituted and unsubstituted bicyclic aryl, substituted and unsubstituted monocyclic heterocycle, substituted and unsubstituted bicyclic heterocycle, substituted and unsubstituted monocyclic heteroaryl, substituted and unsubstituted bicyclic heteroaryl, substituted and unsubstituted monocyclic cycloalkyl, and substituted and unsubstituted bicyclic cycloalkyl;'}{'sub': 2', '5', '6', '7', '2', '3', '2', '3', '2', '3', '5', '6', '1', '6', '1', '6', '1', '6', '7', '1', '6', '1', '6', '1', '6', '2', '3', '2', '3', '2', '3', '1', '3', '1', '3', '1', '3', '1', '8', '1', '8', '1', '8, 'linker is selected from the group consisting of a direct bond, O, S, SO, SO, C═O, CRR, NR, substituted and unsubstituted (C-C) alkyl, substituted and unsubstituted (C-C) heteroalkyl, substituted and unsubstituted (C-C) alkene, substituted and unsubstituted 5 or 6 membered aryl, substituted and unsubstituted 5 or 6 membered heteroaryl, substituted and unsubstituted 3-6 membered cycloalkyl, and substituted and unsubstituted 3-6 membered saturated heterocyclyl; wherein Rand Rare independently selected from the group consisting of hydrogen, (C-C) alkyl, (C-C) heteroalkyl, halogen, (C-C) haloalkyl, cyano, and hydroxyl; Ris selected from the group consisting of hydrogen, (C-C)alkyl, (C-C) haloalkyl, and (C-C) heteroalkyl; substitutions for the (C-C) alkyl, (C-C) heteroalkyl, and (C-C) alkene are selected from the group ...

Подробнее
Номер записи: 79
10-04-2014 дата публикации

PROCESS FOR PREPARING AZOMETHINES FROM ALPHA-OXOCARBOXYLATES, AMINES AND ARYL BROMIDES

Номер: US20140100371A1
Автор: Cotta Matthias, Cotte Alain, Goossen Lukas, Rudolph Felix, Song Bingrui
Принадлежит: Saltigo GmbH

A process for preparing azomethines of the general formula (V) where R is an optionally substituted carbocyclic aromatic radical having 6 to 24 carbon atoms or an optionally substituted alkyl radical or an optionally substituted heteroaromatic radical having 5 to 24 carbon atoms, and Ris an optionally substituted carbocyclic aromatic radical having 6 to 24 carbon atoms or an optionally substituted heteroaromatic radical having 5 to 24 carbon atoms, Ris hydrogen or an optionally substituted carbocyclic aromatic radical having 6 to 24 carbon atoms or an optionally substituted alkyl radical or an optionally substituted cycloalkyl radical N or an optionally substituted heteroaromatic radical having 5 to 24 carbon atoms by reacting alpha-oxo carboxylates of the general formula (I) where n is a number in the range from 1 to 6, Mis a cation, with aryl bromides of the general formula (IV) and amines of the general formula (II) via the alpha-iminocarboxylate intermediate of the general formula (III), in the presence of two transition metals or compounds thereof as catalyst, is described. 2. Process according to claim 1 , where the catalyst comprises two different transition metals and/or transition metal compounds claim 1 , characterized in that one transition metal or one transition metal compound is selected from those able to assume oxidation states differing from one another by one unit claim 1 , and the other transition metal or the other transition metal compound is selected from those able to assume oxidation states differing from one another by two units.3. Process according to either of or claim 1 , where the one transition metal or the transition metal compound is selected from the series of metals Ag claim 1 , Cu claim 1 , Mn claim 1 , Fe claim 1 , Co claim 1 , Ni claim 1 , Mo claim 1 , Ru and compounds thereof and the other transition metal or the other transition metal compound is selected from the series of metals Pd claim 1 , Ni claim 1 , Fe claim 1 , Au claim ...

Подробнее
Номер записи: 80
04-01-2018 дата публикации

Molecules having pesticidal utility, and intermediates, compositions, and processes, related thereto

Номер: US20180000087A1
Автор: Baum Erich W., Benko Zoltan L., CHOY Nakyen, Crouse Gary D., Daeuble, DeKorver Kyle A., Demeter David A., Eckelbarger Joseph D., GRAY KAITLYN, Heemstra Ronald J., Hunter Ricky, JR. Ronald, Knueppel Daniel I., Li Fangzheng, Martin Timothy P., Nissen Jeffrey, Riener Michelle, Ross, Sparks Thomas C., SR. John F., Trullinger Tony K., Vednor Peter, Wessels Frank J., Yap Maurice C.
Принадлежит: DOW AGROSCIENCES LLC

This disclosure relates to the field of molecules having pesticidal utility against pests in Phyla Arthropoda, Mollusca, and Nematoda, processes to produce such molecules, intermediates used in such processes, pesticidal compositions containing such molecules, and processes of using such pesticidal compositions against such pests. These pesticidal compositions may be used, for example, as acaricides, insecticides, miticides, molluscicides, and nematicides. This document discloses molecules having the following formula (“Formula One”). 2. A molecule according to claim 1 , wherein Ris selected from the group consisting of H and Cl.3. A molecule according to claim 1 , wherein Ris selected from the group consisting of H claim 1 , Cl claim 1 , Br claim 1 , CH claim 1 , and CF.4. A molecule according to claim 1 , wherein Ris selected from the group consisting of H claim 1 , F claim 1 , Cl claim 1 , CH claim 1 , CF claim 1 , and OCF.5. A molecule according to claim 1 , wherein Ris selected from the group consisting of H claim 1 , F claim 1 , Cl claim 1 , Br claim 1 , CH claim 1 , and CF.6. A molecule according to claim 1 , wherein R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , and Rare H.7. A molecule according to claim 1 , wherein Ris Cl.8. A molecule according to claim 1 , wherein Ris Cl.9. A molecule according to claim 1 , wherein Ris selected from the group consisting of H claim 1 , Cl claim 1 , and CF.10. A molecule according to claim 1 , wherein Ris selected from the group consisting of H and CH.11. A molecule according to claim 1 , wherein Ris selected from the group consisting of cyclopropyl claim 1 , cyclobutyl claim 1 , cyclopentyl claim 1 , cyclohexyl claim 1 , azetidinyl claim 1 , morpholinyl claim 1 , oxetanyl claim 1 , pyranyl claim 1 , tetrahydrothiophenyl claim 1 , thietanyl claim 1 , thietanyl-oxide claim 1 , and thietanyl-dioxide claim 1 ,{'sub': 3', '3', '3, 'wherein each cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, ...

Подробнее
Номер записи: 81
07-01-2016 дата публикации

NOVEL CARBOXAMIDE COMPOUNDS

Номер: US20160002149A1
Автор: "OSullivan Anthony Cornelius", Cassayre Jerome Yves, Jeanguenat Andre, Loiseleur Olivier
Принадлежит: SYNGENTA PARTICIPATIONS AG

Compounds of the formula (I), in which the substituents are as defined in claim , are suitable for use as nematicides. 2. The compound according to wherein R1 and R2 are each methyl claim 1 , or R1 and R2 form together with the carbon atom claim 1 , to which they are attached claim 1 , a cyclopropyl or cyclobutyl ring claim 1 ,3. The compound according to wherein Y is C—H or N.4. The compound according to claim 1 , wherein R3 is claim 1 , independently of each other claim 1 , selected from a halogen claim 1 , cyano claim 1 , C1-C2-alkyl and C1-C2-haloalkyl.5. The compound according to claim 1 , wherein R8 is claim 1 , independently selected from claim 1 , a halogen claim 1 , cyano claim 1 , C1-C2-alkyl claim 1 , or C1-C2-haloalkyl.6. The compound according to claim 1 , wherein p is 0 claim 1 , 1 or 2.7. The compound according to claim 1 , wherein m is 0 or 1.11. A Pesticidal composition claim 1 , which claim 1 , in addition to comprising formulation adjuvants claim 1 , comprises a nematicidal effective amount of a compound according to .12. A composition according to claim 11 , which further comprises one or more insecticidally claim 11 , acaricidally claim 11 , nematicidally and/or fungicidally active agents.13. A method of controlling damage and/or yield loss caused by a pest and/or fungi which comprises applying to a pest claim 1 , to a locus of a pest claim 1 , or to a plant susceptible to attack by a pest and/or fungi or to a plant propagation material an effective amount of a compound of formula (I) as defined in .14. A method for the protecting plant propagation material from damage and/or yield loss caused by a pest and/or fungi which comprises applying to the propagation material or the site claim 1 , where the propagation material is planted claim 1 , an effective amount of a compound of formula (I) as defined in .15. The method according to wherein the damage or loss is caused by a nematode pest.16. A treated plant propagation material claim 1 , wherein ...

Подробнее
Номер записи: 82
07-01-2016 дата публикации

Process for Preparing Atazanavir Sulphate

Номер: US20160002166A1
Автор: CHINIMILLI Venugopalarao, KANKAN Rajendra Narayanrao, PATHI Srinivas Laxminarayan
Принадлежит:

The present invention relates to a process for the preparation of Compound (A): 2. The process according to claim 1 , wherein the combination of two or more solvents comprises a first solvent that is a water immiscible claim 1 , or moderately soluble in water claim 1 , solvent claim 1 , and a second solvent that is a water miscible solvent.3. The process according to claim 1 , wherein the combination of two or more solvents comprises a water miscible solvent that is a polar protic solvent or a polar aprotic solvent.4. The process according to claim 1 , wherein the combination of two or more solvents comprises a first solvent that is water immiscible claim 1 , or moderately soluble in water claim 1 , solvent and a second solvent that is a water miscible and polar aprotic or polar protic solvent.5. The process according to claim 1 , wherein the combination of two or more solvents comprises a water immiscible claim 1 , or moderately soluble in water claim 1 , solvent that is selected from the group consisting of: esters claim 1 , ethers and hydrocarbons.6. The process according to claim 1 , wherein the combination of two or more solvents comprises a water immiscible claim 1 , or moderately soluble in water claim 1 , solvent that is selected from the group consisting of: ethyl acetate claim 1 , isopropyl acetate claim 1 , and isobutyl acetate.7. The process according to claim 1 , wherein the combination of two or mote solvents comprises a water miscible solvent that is selected from the group consisting of: alcohol claim 1 , dimethylsulfoxide claim 1 , and dimethylformamide.8. The process according to claim 1 , wherein the combination of two or more solvents comprises two solvents.9. The process according to claim 8 , wherein the combination of solvents comprises a first solvent that is a water immiscible claim 8 , or moderately soluble in water claim 8 , solvent claim 8 , and a second solvent that is a water miscible solvent claim 8 , and wherein the ratio of first ...

Подробнее
Номер записи: 83
05-01-2017 дата публикации

BIPYRIDYL COMPOUND

Номер: US20170001960A1
Автор: IDA Haruka, KANAI Motomu, KUNINOBU Yoichiro, NISHI Mitsumi
Принадлежит: JAPAN SCIENCE AND TECHNOLOGY AGENCY

There are provided a compound capable of being a novel ligand allowing regioselective borylation to be performed in the aromatic borylation reaction, and a catalyst using the same compound. There is provided a bipyridyl compound represented by a general formula (): (wherein A represents a single bond, a vinylene group or an ethynylene group; 2. The bipyridyl compound according to claim 1 , wherein A is a single bond.3. The bipyridyl compound according to claim 1 , wherein Ris a hydrogen atom claim 1 , a halogen atom claim 1 , an alkyl group having 1 to 10 carbon atoms claim 1 , an alkenyl group having 2 to 10 carbon atoms claim 1 , a cycloalkyl group having 3 to 7 carbon atoms claim 1 , an aryl group having 6 to 10 carbon atoms claim 1 , an aryloxy group having 6 to 10 carbon atoms claim 1 , an alkoxy group having 1 to 10 carbon atoms claim 1 , a Calkylamino group claim 1 , a di(Calkyl)amino group or a Calkoxycarbonyl group.4. The bipyridyl compound according to claim 1 , wherein Ris a hydrogen atom claim 1 , an optionally substituted alkyl group having 1 to 10 carbon atoms claim 1 , an optionally substituted alkenyl group having 2 to 10 carbon atoms claim 1 , an optionally substituted cycloalkyl group having 3 to 7 carbon atoms claim 1 , an optionally substituted aryl group having 6 to 10 carbon atoms claim 1 , an optionally substituted alkoxy group having 1 to 10 carbon atoms or an optionally substituted aryloxy group having 6 to 10 carbon atoms.5. An aromatic borylation catalyst comprising the bipyridyl compound according to as a ligand.6. The catalyst according to claim 5 , wherein the bipyridyl compound is coordinated to iridium. The present invention relates to a bipyridyl compound useful as a ligand of a metal catalyst and a catalyst including the same bipyridyl compound as a ligand.The Suzuki-Miyaura reaction performing a cross coupling between an organic halogen compound and an organic boron compound is an important method for carbon-carbon bond formation ...

Подробнее
Номер записи: 84
05-01-2017 дата публикации

OXIME ETHER ACETATE COMPOUND, PREPARATION METHOD THEREFOR AND WEEDING APPLICATION THEREOF

Номер: US20170001961A1
Автор: DU XIAOHUA, MAO DAJIE, XU ZHENYUAN
Принадлежит: Zhejiang University of Technology

The present invention discloses an oxime ether acetate compound containing a phenylpyridine moiety of formula (I), whose preparation method is as follows: (1) mixing a compound of formula (IV), a compound of formula (V), an alkaline substance A, a palladium catalyst and a solvent A; subjecting the mixture to a reaction at the temperature ranging from −10° C. to the reflux temperature for 0.5-20 hours to obtain a reaction solution A; post-treating the solution A to obtain a compound of formula (II); (2) mixing the compound of formula (II), an alkaline substance B, a phase transfer catalyst and a solvent B; subjecting the mixture to a reaction at the temperature ranging from −10° C. to the reflux temperature for 0.1-2 hours; then adding a compound of formula (III), continuing to react at the temperature ranging from −10° C. to the reflux temperature for 0.5-20 hours to obtain a reaction solution B; and post-treating the solution B to obtain the compound of formula (I). The oxime ether acetate compound containing a phenylpyridine moiety of formula (I) can be used for weeding in crops. 3. The oxime ether acetate compound according to claim 1 , wherein X is O.4. The oxime ether acetate compound according to claim 3 , wherein R on the pyridine ring is selected from the group consisting of Br claim 3 , Cl claim 3 , F claim 3 , CN claim 3 , CFand NO; when 0 Подробнее

Номер записи: 85
04-01-2018 дата публикации

(THIO, OXO, AND SELENO) SEMICARBAZONE COMPLEXES WITH ZINC AND THEIR USE FOR TREATING CANCER

Номер: US20180002279A1
Автор: Augeri David J., Bencivenga Anthony F., Blanden Adam, Carpizo Darren R., Gilleran John A., Kimball Spencer David, Loh Stewart N., Yu Xin
Принадлежит:

The invention provides organic complexes of Zn of formula (I) that are useful for treating cancer, as well as compositions and kits comprising such complexes, and intermediate monomer compounds that are useful for the preparation of such complexes. 4. The complex of any one of - wherein the ratio of the number of compounds of formula (I) or ions or poly-ions thereof to zinc Zn ions is about 2:1; or a solvate thereof.8. A pharmaceutical composition , comprising a complex of any one of - or a solvate thereof , and a pharmaceutically acceptable carrier.9. An injectable pharmaceutical formulation comprising , a complex of any one of - or a solvate thereof , and a pharmaceutically acceptable carrier.10. A method of inhibiting cancer cell growth in vivo or in vitro , comprising contacting a cancer cell with a complex of any one of - or a solvate thereof.11. A method of treating cancer in an animal comprising administering a complex of any one of - or a solvate thereof to the animal.12. The method of claim 11 , further comprising administering zinc to the animal.13. The method of any one of - claim 11 , wherein the cancer is caused by mutations affecting zinc binding proteins.14. The method of any one of - claim 11 , wherein the cancer is associated with a zinc binding p53 mutation.15. The method of any one of - claim 11 , wherein the cancer is associated with a zinc binding p53 mutation selected from R175 claim 11 , C176 claim 11 , H179 claim 11 , C238 claim 11 , C242 claim 11 , and G245.16. A complex of any one of - or a solvate thereof for use in medical treatment.17. A complex of any one of - or a solvate thereof for the prophylactic or therapeutic treatment of cancer.18. The complex or solvate of wherein the cancer is caused by mutations affecting zinc binding proteins.19. The complex or solvate of claim 17 , wherein the cancer is associated with a zinc binding p53 mutation.20. The complex or solvate of claim 17 , wherein the cancer is associated with a zinc binding ...

Подробнее
Номер записи: 86
04-01-2018 дата публикации

(THIO, OXO, AND SELENO) SEMICARBAZONE DERIVATIVES AND THEIR USE FOR TREATING CANCER

Номер: US20180002280A1
Автор: Augeri David J., Bencivenga Anthony F., Blanden Adam, Carpizo Darren R., Gilleran John A., Kimball Spencer David, Loh Stewart N., Yu Xin
Принадлежит:

The invention provides compounds of formula I and II and salts thereof, wherein R, R, Y, R, and Rhave any of the meanings described in the specification, as well as compositions comprising such compounds and salts, and methods for treating cancer using such compounds and salts. 3. A pharmaceutical composition , comprising , a compound of or or a pharmaceutically acceptable salt thereof , and a pharmaceutically acceptable carrier.4. An injectable pharmaceutical formulation comprising , a compound of or or a pharmaceutically acceptable salt thereof , and a pharmaceutically acceptable carrier.5. A method of inhibiting cancer cell growth in vivo or in vitro , comprising contacting a cancer cell with a compound of any one of - or a pharmaceutically acceptable salt thereof.6. A method of treating cancer in an animal comprising administering a compound of any one of - or a pharmaceutically acceptable salt thereof to the animal.7. The method of claim 6 , further comprising administering zinc to the animal.8. The method of any one of - claim 6 , wherein the cancer is caused by mutations affecting zinc binding proteins.9. The method of any one of - claim 6 , wherein the cancer is associated with a zinc binding p53 mutation.10. The method of any one of - claim 6 , wherein the cancer is associated with a zinc binding p53 mutation selected from R175 claim 6 , C176 claim 6 , H179 claim 6 , C238 claim 6 , C242 claim 6 , and G245.11. A compound of any one of - or a pharmaceutically acceptable salt thereof claim 6 , for use in medical treatment.12. A compound of any one of - or a pharmaceutically acceptable salt thereof claim 6 , for the prophylactic or therapeutic treatment of cancer.13. The compound or pharmaceutically acceptable salt of wherein the cancer is caused by mutations affecting zinc binding proteins.14. The compound or pharmaceutically acceptable salt of claim 13 , wherein the cancer is associated with a zinc binding p53 mutation.15. The compound or pharmaceutically ...

Подробнее
Номер записи: 87
02-01-2020 дата публикации

BIARYL COMPOUND, PREPARATION METHOD AND USE THEREOF

Номер: US20200002280A1
Автор: Huang Yafei, Qiu Ruomeng, Tang Ting, Wang Yonghui
Принадлежит:

The present invention belongs to the technical field of chemical pharmaceuticals, and relates to a compound represented by general formula (I) or formula (II) and a preparation method thereof. The compounds are biaryl derivatives with RORγt activation activity. The biaryl derivatives disclosed in this invention can effectively activate the RORγt protein receptor, and thereby promote the differentiation of Th17 cells and increasing the production of IL-17, which can be used as an immune modulator for the treatment of various cancers or viral infection-related diseases. 2. The compound of Formula (I) or (II) or the pharmaceutically acceptable salt thereof according to claim 1 , wherein:{'sub': 1', '2', '3', '3', '5', '3', '6', '3', '6', '9', '10', '1', '2', '3', '2', '6', '3', '7', '1', '2', '3', '2', '6, 'claim-text': {'sub': 9', '10', '1', '6', '3', '6', '3', '8', '9', '10, 'wherein, R, Rare each independently selected from a group consisting of hydrogen, C-Calkyl, C-Ccycloalkyl and C-Cheterocycloalkyl, or Rand Rform a cyclic group having four to seven ring members together with the nitrogen atom to which they attach; the cyclic group contains or does not contain a second heteroatom selected from oxygen as a ring member.'}, 'R, Rand Rare each independently selected from a group consisting of hydrogen, C-Calkyl, C-Ccycloalkyl, C-Cheterocycloalkyl containing one oxygen atom, and —NRR, or any two of R, Rand Rform C-Calkyl alkenyl or C-Ccycloalkyl alkenyl, or R, Rand Rform C-Calkyl alkynyl;'}3. The compound of Formula (I) or (II) or the pharmaceutically acceptable salt thereof according to claim 2 , wherein Ris selected from a group consisting of C-Calkyl claim 2 , C-Ccycloalkyl claim 2 , C-Coxoheterocycloalkyl claim 2 , phenyl substituted with one or more R; pyridyl substituted with one or more R; pyrimidinyl substituted with one or more R; pyridone substituted with one or more R claim 2 , pyrazolyl substituted with one or more R claim 2 , pyrrolyl substituted with one ...

Подробнее
Номер записи: 88
03-01-2019 дата публикации

13-Cis-RAMBA RETINAMIDES THAT DEGRADE MNKs FOR TREATING CANCER

Номер: US20190002411A1
Автор: Mbatia Hannah, Njar Vincent, Ramalingam Senthilmurugan, Ramamurthy Vidya
Принадлежит: University of Maryland, Baltimore

The synthesis and in vitro and in vivo anti-breast and anti-prostate cancers activities of novel C-4 heteroaryl 13-cis retinamides that modulate Mnk-eIF4E and AR signaling are discussed. In both breast and prostate cancer cell lines, these compounds induce Mnk1/2 degradation to substantially suppress eIF4E phosphorylation. In prostate cancer cells, the compounds induce degradation of both full-length androgen receptor (fAR) and splice variant AR (AR-V7) to inhibit AR transcriptional activity. The consequences of these multiple activities resulted in inhibition of cell growth and migration and induction of apoptosis. Finally and importantly, the compounds demonstrate strong in vitro and in vivo anti-breast and anti-prostate cancer activities, with no apparent host toxicities. 2. The process as claimed in claim 1 , wherein the process is for the treatment of breast cancer or prostate cancer.3. The process as claimed in claim 2 , wherein R is an imidazole claim 2 , and wherein the compound is selected from the following:Compound 16 in which R′ is the hydrogen, and n is 0;Compound 17 in which R′ is a hydroxyl group in a para-position, and n is 0;Compound 18 in which R′ is a hydroxyl group in an ortho-position, and n is 0;Compound 19 in which R′ is a fluorine in a para-position, and n is 0;Compound 20 in which R′ is a fluorine in a meta-position, and n is 0;Compound 21 in which R′ is the hydrogen, and n is 1;Compound 22 in which R′ is the hydroxyl group in the para-position, and n is 1;Compound 23 in which R′ is the fluorine in the para-position, and n is 1;Compound 24 in which R′ is the fluorine in the meta-position, and n is 1; andCompound 25 in which R′ is the hydroxyl group in the para-position, and n is 2.4. The process as claimed in claim 3 , wherein the compound is selected from the following:Compound 16 in which R′ is the hydrogen, and n is 0;Compound 20 in which R′ is a fluorine in a meta-position, and n is 0; andCompound 22 in which R′ is the hydroxyl group in ...

Подробнее
Номер записи: 89
07-01-2021 дата публикации

Substituted Aromatic Compounds and Pharmaceutical Uses Thereof

Номер: US20210002202A1
Автор: BIENVENU Jean-Francois, GAGNON Lyne, GROUIX Brigitte, Penney Christopher, PERRON Valérie, ZACHARIE Boulos
Принадлежит:

The present invention relates to substituted aromatic compounds of Formula I and their pharmaceutical uses. Particular aspects of the invention relate to the use of those compounds in the prevention and/or treatment of various diseases and conditions in subjects, including the prevention or treatment of (i) blood disorders, (ii) renal disorders, a nephropathies, or renal disorder complications; (iii) inflammatory-related diseases; and/or (iv) oxidative stress related disorders. 2. The method of claim 1 , wherein Ris straight chain Calkyl claim 1 , Calkyl claim 1 , or C-Calkenyl; and Ris H claim 1 , halogen claim 1 , haloalkyl claim 1 , or OR.3. The method of claim 1 , wherein Ris independently chosen from: H claim 1 , halogen claim 1 , haloalkyl claim 1 , straight chain C-Calkyl claim 1 , or OR; and Ris independently chosen from: H claim 1 , halogen claim 1 , haloalkyl claim 1 , C-Calkyl claim 1 , or OR.4. The method of claim 1 , wherein Ris OR.5. The method of claim 1 , wherein the pharmaceutically acceptable salt is a base addition salt.6. The method of claim 5 , wherein the base addition salt is a metal counterion.7. The method of claim 6 , wherein the metal counterion is sodium claim 6 , magnesium claim 6 , calcium claim 6 , potassium or lithium.8. The method of claim 7 , wherein the metal counterion is sodium.11. The method of claim 1 , wherein the inflammatory-related disease is an immune mediated inflammatory disease or an autoimmune disease.12. The method of claim 1 , wherein the inflammatory-related disease is an autoimmune disease.13. The method of claim 1 , wherein the inflammatory-related disease is selected from the group consisting of arthritis claim 1 , systemic lupus erythematosus (SLE) claim 1 , ITP claim 1 , glomerulonephritis claim 1 , vasculitis claim 1 , psoriatic arthritis claim 1 , psoriasis claim 1 , Crohn's disease claim 1 , inflammatory bowel disease claim 1 , ankylosing spondylitis claim 1 , Sjögren's syndrome claim 1 , Still's disease ...

Подробнее
Номер записи: 90
03-01-2019 дата публикации

In Vivo Methods for Enhancing Bioenergetic Status in Female Germ Cells

Номер: US20190002919A1
Автор: SINCLAIR DAVID A., TILLY JONATHAN L.
Принадлежит:

In vivo methods using bioenergetic agents for restoring the quality of aged oocytes, enhancing oogonial stem cells or improving derivatives thereof (e.g., cytoplasm or isolated mitochondria) for use in fertility-enhancing procedures, are described. 1. A method of improving fertility in a female mammalian subject in need thereof , said method comprising administering to the female mammalian subject one or more bioenergetics agents in an amount effective to enhance the bioenergetic status of an oocyte or an oogonial stem cell (OSC) of the female mammalian subject , thereby improving fertility in the female mammalian subject.2. The method of claim 1 , wherein the bioenergetic agent is selected from the group consisting of a CD38 inhibitor claim 1 , a nicotinamide adenine dinucleotide (NAD) precursor and combinations thereof.3. The method of claim 2 , wherein the CD38 inhibitor is a compound selected from the group consisting of 1-[(2-Acetoxyethoxy)methyl]-3-(aminocarbonyl)-pyridinium chloride claim 2 , 1-[(2-Benzyloxyethoxy)methyl]-3-(aminocarbonyl)-pyridinium chloride claim 2 , 1{[2-(4-Methoxy-phenoxy)ethoxy]methyl}-3-(aminocarbonyl)-pyridinium chloride claim 2 , 1-{[2-(4-Phenoxy-phenoxy)ethoxy]methyl}-3-(aminocarbonyl)-pyridinium chloride claim 2 , 1-{[2-(4-Nitro-phenoxy)ethoxy]methyl}-3-(aminocarbonyl)-pyridinium chloride claim 2 , 1-{[2-(3-Trifluoromethyl-phenoxy)ethoxy]methyl}-3-(aminocarbonyl)-pyridinium chloride claim 2 , 1-{[2-(8′-Quinolyloxy)ethoxy]methyl}-3-(aminocarbonyl)-pyridinium chloride claim 2 , 1 claim 2 ,2-Dimethoxy-ethylene-bis-N claim 2 ,N′-3-(aminocarbonyl)-pyridinium dichloride claim 2 , 1 claim 2 ,4-Dimethoxy-butylene-bis-N claim 2 ,N′-3-(aminocarbonyl)-pyridinium dichloride claim 2 , 1 claim 2 ,4-Dimethoxy-butyne-bis-N claim 2 ,N′-3-(aminocarbonyl)-pyridinium dichloride claim 2 , 1 claim 2 ,4-Dimethoxy-hexamethylene-bis-N claim 2 ,N′-3-(aminocarbonyl)-pyridinium dichloride claim 2 , (E)-1-{[4-(8′-Quinolyloxy)but-2-enyloxy]methyl}-3-( ...

Подробнее
Номер записи: 91
01-01-2015 дата публикации

NOVEL HETEROARYLAMIDE DERIVATIVES HAVING ANTIANDROGENIC PROPERTIES

Номер: US20150005308A1
Автор: Koistinaho Milla, Muona Anu, Ratilainen Jari
Принадлежит:

The invention relates to novel heteroarylamide derivatives having formula (I) and N-oxides, stereoisomers and pharmaceutically acceptable salts thereof, where R, R, R1 1, R′, R″, z and X are as defined in the claims. The arylamide derivatives of formula (I) have antiandrogenic properties. The invention also relates to compounds of formula (I) for use as a medicament and to pharmaceutical compositions comprising them and to their preparation. 7. Heteroarylamide derivative according to claim 6 , where R1″ claim 6 , R4″ claim 6 , R5″ claim 6 , R6 and R10 are hydrogen; R2″ is trifluoromethyl or halo claim 6 , especially chloro; R3″ is cyano; R8 is CFor halo claim 6 , especially chloro or fluoro; R9 is hydrogen or halo claim 6 , especially fluoro; z is 0 or 1 (R′═R″═H); X is SO; and R11 is alkyl claim 6 , especially methyl claim 6 , ethyl claim 6 , tert-butyl claim 6 , cyclopropyl claim 6 , isopropyl claim 6 , or isopentyl claim 6 , or phenyl or pyridinyl optionally substituted with halo claim 6 , especially chloro claim 6 , when z is 0 claim 6 , or phenyl optionally substituted with halo claim 6 , especially chloro claim 6 , when z is 1.9. Heteroarylamide derivative according to claim 8 , where R1 claim 8 , R5 claim 8 , R6′ claim 8 , R7′ and R10′ are hydrogen; R2 is trifluoromethyl or halo claim 8 , especially chloro; R3 is cyano; R8′ is halo claim 8 , especially chloro or fluoro; R9′ is hydrogen or halo claim 8 , especially fluoro; z is 0; X is SO; and R11 is alkyl claim 8 , especially methyl claim 8 , ethyl claim 8 , tert-butyl claim 8 , cyclopropyl claim 8 , isopropyl claim 8 , or isopentyl.11. Heteroarylamide derivative according to claim 10 , where R1 claim 10 , R5 claim 10 , R6 claim 10 , R7 and R10 are hydrogen; R2 is trifluoromethyl or halo claim 10 , especially chloro; R3 is cyano; R8 is halo claim 10 , especially chloro or fluoro; R9 is hydrogen or halo claim 10 , especially fluoro; z is 0; X is SO; and R11 is alkyl claim 10 , especially isopropyl.12. ...

Подробнее
Номер записи: 92
11-01-2018 дата публикации

Molecules having pesticidal utility, and intermediates, compositions, and processes, related thereto

Номер: US20180007911A1
Автор: Baum Erich W., Benko Zoltan L., CHOY Nakyen, Crouse Gary D., Daeuble, DeKorver Kyle A., Demeter David A., Eckelbarger Joseph D., Heemstra Ronald J., Hunter Ricky, JR. Ronald, Knueppel Daniel I., Li Fangzheng, Martin Timothy P., Nissen Jeffrey, Riener Michelle, Ross, Sparks Thomas C., SR. John F., Trullinger Tony K., Vednor Peter, Wessels Frank J., Yap Maurice C.
Принадлежит: DOW AGROSCIENCES LLC

This disclosure relates to the field of molecules having pesticidal utility against pests in Phyla Arthropoda, Mollusca, and Nematoda, processes to produce such molecules, intermediates used in such processes, pesticidal compositions containing such molecules, and processes of using such pesticidal compositions against such pests. These pesticidal compositions may be used, for example, as acaricides, insecticides, miticides, molluscicides, and nematicides. This document discloses molecules having the following formula (“Formula One”). 2. A molecule according to claim 1 , wherein Ris selected from the group consisting of H claim 1 , F claim 1 , and Cl.3. A molecule according to claim 1 , wherein Ris selected from the group consisting of H claim 1 , F claim 1 , and Cl.4. A molecule according to claim 1 , wherein Ris F or Cl.5. A molecule according to claim 1 , wherein R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , and Rare each independently H.6. A molecule according to claim 1 , wherein Ris selected from the group consisting of Cl and Br.7. A molecule according to claim 1 , wherein Ris selected from the group consisting of Cl and Br.8. A molecule according to claim 1 , wherein Ris selected from the group consisting of H claim 1 , Cl claim 1 , and CF.9. A molecule according to claim 1 , wherein Ris selected from the group consisting of H and CH.10. A molecule according to claim 1 , wherein Ris selected from the group consisting of CH claim 1 , CHCH claim 1 , CHCHCH claim 1 , CHCHCHCH claim 1 , CHCHCHOCHCH claim 1 , CH claim 1 , CHCH claim 1 , CHCHCH claim 1 , CHCHCHCH claim 1 , CHCHCHCHCH claim 1 , CHCHCHCHCHCH claim 1 , CHCH(CH) claim 1 , CHcyclopropyl claim 1 , CHCHcyclopropyl claim 1 , CHcyclobutyl claim 1 , CHphenyl claim 1 , CHCHphenyl claim 1 , CHC═CH claim 1 , CHC═CH claim 1 , CHCF claim 1 , CHCHF claim 1 , CHCHCF claim 1 , CHCFCF claim 1 , CHCHCHCF claim 1 , CHCHCFCF claim 1 , CHCFCFCF claim 1 , CHCHCHCHF claim 1 , CHCHSCH ...

Подробнее
Номер записи: 93
10-01-2019 дата публикации

Bis-amines, Compositions, and Uses Related to CXCR4 Inhibition

Номер: US20190008840A1
Автор: Hyunsuk Shim, Renren Bai, Suazette Reid MOORING
Принадлежит: EMORY UNIVERSITY, Georgia State University Research Foundation Inc

This disclosure relates bis-amine compounds disclosed herein and uses related to CXCR4 inhibition. In certain embodiments, the compounds have formula (I), salts, derivatives, and prodrugs thereof wherein, A is a bridging aryl or heterocyclyl and R1 and R2 are further disclosed herein. In certain embodiments, the disclosure contemplates pharmaceutical compositions comprising compounds disclosed herein. In certain embodiments, the disclosure relates to methods of treating or preventing CXCR4 related diseases or conditions by administering an effective amount of a compound disclosed herein to a subject in need thereof.

Подробнее
Номер записи: 94
09-01-2020 дата публикации

CATECHOL O-METHYLTRANSFERASE ACTIVITY INHIBITING COMPOUNDS

Номер: US20200009103A1
Автор: AHLMARK Marko, DIN BELLE David, KAUPPALA Mika, LUIRO Anne, MESSINGER Josef, PAJUNEN Taina, PYSTYNEN Jamo, TIAINEN Eija, VAISMAA Matti
Принадлежит:

Compounds of formula (I), wherein Ris as defined in the claims, exhibit COMT enzyme inhibiting activity and are thus useful as COMT inhibitors. Methods of treatment and pharmaceutical dosage forms are also disclosed. 127-. (canceled)29. The method of claim 28 , wherein the compound of formula I is (E)-4 claim 28 ,5-dihydroxy-2-(pent-1-enyl)isophthalonitrile claim 28 , (E)-2-(3 claim 28 ,3-dimethylbut-1-enyl)-4 claim 28 ,5-dihydroxyisophthalonitrile claim 28 , (Z)-4 claim 28 ,5-dihydroxy-2-(prop-1-enyl)isophthalonitrile claim 28 , (E)-4 claim 28 ,5-dihydroxy-2-(prop-1-enyl)isophthalonitrile claim 28 , (Z)-2-(but-2-enyl)-4 claim 28 ,5-dihydroxyisophthalonitrile claim 28 , 4 claim 28 ,5-dihydroxy-2-(3-methylbut-2-enyl)isophthalonitrile claim 28 , (E)-2-(but-2-enyl)-4 claim 28 ,5-dihydroxyisophthalonitrile claim 28 , 4 claim 28 ,5-dihydroxy-2-(2-methylprop-1-enyl)isophthalonitrile claim 28 , 4 claim 28 ,5-dihydroxy-2-vinylisophthalonitrile claim 28 , 4 claim 28 ,5-dihydroxy-2-(prop-1-en-2-yl)isophthalonitrile claim 28 , 2-allyl-4 claim 28 ,5-dihydroxyisophthalonitrile claim 28 , 4 claim 28 ,5-dihydroxy-2-(3-methylbut-2-en-2-yl)isophthalonitrile or (E)-4 claim 28 ,5-dihydroxy-2-(4-methylpent-1-enyl)isophthalonitrile.30. The method of claim 28 , wherein the disease or condition is hypertension claim 28 , heart failure claim 28 , depression claim 28 , diabetic vascular dysfunction claim 28 , pain claim 28 , or restless leg syndrome.31. The method of claim 28 , wherein the mammal is a human. The present invention relates to pharmacologically active 2-substituted 4,5-dihydroxyisophthalonitriles, or pharmaceutically acceptable salts and esters thereof, as well as to pharmaceutical compositions containing them and to their use as inhibitors of the catechol O-methyltransferase (COMT) enzyme.Dopamine is deficient in the brain of patients suffering from Parkinson's disease. Levodopa is used orally in the treatment of Parkinson's disease. Levodopa is a dopamine precursor, which is ...

Подробнее
Номер записи: 95
11-01-2018 дата публикации

Substituted 2-[3-(1-methyl-piperidin-4-yl)-propylamino]-pyrimidine-5-carboxylic acids and amides and methods of making the same

Номер: US20180009783A1
Автор: Diego Broggini, Guangrong Tang, Lucie Lovelle, Matteo Conza, Oliver FLÖGEL, Stefan Horns, Susanne Lochner, Zhaobin Wang
Принадлежит: Janssen Pharmaceutica NV

The present invention relates to certain intermediates useful in the preparation of certain benzoimidazol-2-yl pyrimidines and processes for preparing them. In particular, the present invention relates to various 2-[3-(1-methyl-piperidin-4-yl)-propylamino]-pyrimidine-5-carboxylic acids and amides as useful intermediates in the preparation of compounds including

Подробнее
Номер записи: 96
08-01-2015 дата публикации

THERAPEUTIC CURCUMIN DERIVATIVES

Номер: US20150011494A1
Автор: Abcouwer Steve F., Bobrovnikova-Marjon Ekaterina V., Deck Lorraine M., Hunsaker Lucy A., Orlando Robert A., Royer Robert E., Vander Jagt David L., Weber Waylon M.
Принадлежит:

Curcumin analogues and methods are provided for treatment of disease. 114-. (canceled)15. A method for identifying a therapeutic curcumin derivative , comprising:contacting a cell comprising at least one of NF-κB, AP-1 or GSTP1-1 with a curcumin derivative;contacting the cell with an activator of NF-κB, AP-1 or GSTP1-1; anddetermining the effect of the curcumin derivative on cell activation;wherein a curcumin derivative that reduces cell activation is identified as an therapeutic curcumin derivative.16. The method of claim 15 , wherein the activator comprises TNF-α claim 15 , IL-1 claim 15 , PMA or an MAPK kinase.17. The method of claim 15 , wherein the cell is an adipocyte or endothelial cell.18. The method of claim 15 , wherein the cell is a brain cell.19. The method of claim 18 , wherein the brain cell is a glial cell.20. A method for identifying a therapeutic curcumin derivative claim 18 , comprising:contacting a solution comprising an Aβ peptide with a curcumin derivative; anddetermining the effect of the curcumin derivative on aggregation of the Aβ peptide;wherein a curcumin derivative that reduces aggregation of the Aβ peptide is identified as a therapeutic curcumin derivative.21. The method of claim 20 , wherein the effect of the curcumin derivative on aggregation of the Aβ peptide is determined by an immunological assay.22. A method of treating a subject afflicted with cancer or a precancerous condition claim 20 , the method comprising administering to the subject a therapeutically effective amount of a composition comprising a curcumin derivative selected from the group consisting of:{'sup': 1', '2', '1', '2, '(a) Ar-L-Ar(Formula I); wherein L is a divalent linking group comprising an alkylene or an alkenylene comprising 3, 4, 5, 6, or 7 backbone carbon atoms, wherein one or more of the backbone carbon atoms form part of a carbonyl or secondary alcohol; and Arand Arare each independently aryl groups; and'}{'sup': 1', '11', '1', '11, '(b) Ar-L-R(Formula IV ...

Подробнее
Номер записи: 97
14-01-2021 дата публикации

COMPOUND FOR MODULATING DDAH AND ADMA LEVELS, AS WELL AS METHODS OF USING THEREOF TO TREAT DISEASE

Номер: US20210009498A1
Автор: FOWLER Kerry, Singh Jaipal
Принадлежит:

Disclosed are compounds that can modulate DDAH and the amount of asymmetric dimethylarginine (ADMA) in a subject. Also provided are pharmaceutical compositions comprising these compounds, as well as methods of using these compositions to treat and/or prevent diseases associated with elevated or low levels of DDAH and ADMA. 2. The method of claim 1 , wherein Y is a substituted or unsubstituted aryl ring claim 1 , optionally wherein Y is selected from an oxazole ring claim 1 , a pyridinyl ring claim 1 , a thiazole ring claim 1 , and a thiophene ring.5. The method of claim 4 , wherein Xand Xarei) both CH;{'sub': '2', 'ii) independently O or CHor'}iii) together with the bond to which they are attached form a 3-membered carbocyclic ring.7. The method of claim 1 , wherein Xand Xtogether with the bond to which they are attached forms a 3-membered carbocyclic ring.8. (canceled)9. The method of wherein said composition is administered for treating or preventing a disease or condition associated with elevated levels of asymmetric dimethylarginine (ADMA) in a subject.10. The method of claim 9 , wherein the risk factors claim 9 , disease or condition includes hypertension claim 9 , heart failure claim 9 , pulmonary arterial hypertension claim 9 , erectile dysfunction claim 9 , coronary and peripheral arterial disease claim 9 , renal disease claim 9 , insulin resistance claim 9 , diabetes claim 9 , atrial fibrillation claim 9 , sickle cell disease claim 9 , organ damage claim 9 , sepsis claim 9 , renal failure claim 9 , endothelial dysfunction claim 9 , vascular disease claim 9 , or a combination thereof.11. The method of wherein said composition is administered for reducing fibrosis in a cell or tissue.1213-. (canceled)14. The method of claim 11 , wherein the fibrosis is associated with a fibrotic condition of the lung claim 11 , a fibrotic condition of the liver claim 11 , a fibrotic condition of the heart or vasculature claim 11 , a fibrotic condition of the kidney claim 11 , ...

Подробнее
Номер записи: 98
08-01-2015 дата публикации

ANTIMICROBIAL AGENTS

Номер: US20150011559A1
Автор: Kaul Malvika, LaVoie Edmond J., Parhi Ajit, Pilch Daniel S., Zhang Yongzheng
Принадлежит:

The invention provides methods of treating a bacterial infection in a mammal comprising administering to the mammal a compound of formula I: 2. The method of wherein ring A is phenyl claim 1 , which is substituted with one or more Rand which is optionally substituted with one or more R.3. The method of wherein ring A is thiazolyl claim 1 , which is substituted with one or more Rand which is optionally substituted with one or more R.4. The method of wherein Ris methyl claim 1 , phenyl claim 1 , tert-butyl claim 1 , bromo claim 1 , cyclohexyl claim 1 , thiazolyl claim 1 , biphenyl claim 1 , thiazol-2-ylaminocarbonyl claim 1 , or cyclopropyl.5. The method of wherein B is phenyl substituted with one or more Rand optionally substituted with one or more R.6. The method of wherein B is pyridyl substituted with one or more Rand optionally substituted with one or more R.7. The method of wherein B is thiazolyl substituted with one or more Rand optionally substituted with one or more R.9. The method of wherein each Ris selected from methoxy claim 1 , methyl claim 1 , N claim 1 ,N-dimethylaminomethyl claim 1 , bromo claim 1 , 4-tert-butylphenyl claim 1 , 4-trifluoromethoxy-2-methoxyphenyl claim 1 , nitro claim 1 , amino claim 1 , methylsulfonylamino claim 1 , methylcarbonylamino claim 1 , hydroxymethyl claim 1 , 2-(N claim 1 ,N-diethylamino)ethylaminocarbonyl claim 1 , methoxy claim 1 , —(OCHCH)—OCH claim 1 , 2 claim 1 ,2-dibromoethyl claim 1 , thiazol-2-ylaminocarbonyl claim 1 , and methoxycarbonyl.10. The method of wherein each Ris selected from methoxy claim 1 , N claim 1 ,N-dimethylaminomethyl claim 1 , bromo claim 1 , 4-tert-butylphenyl claim 1 , 4-trifluoromethoxy-2-methoxyphenyl claim 1 , nitro claim 1 , and methoxycarbonyl.13. The method of wherein each Ris independently selected from cyclopropyl claim 12 , tert-butyl claim 12 , bromo claim 12 , 4-tert-butylphenyl claim 12 , and phenyl that is substituted at the 4-position with halo.14. The method of wherein each Ris ...

Подробнее
Номер записи: 99
10-01-2019 дата публикации

ANTIFUNGAL COMPOUND PROCESS

Номер: US20190010140A1
Автор: Alimardanov Asaf, Behnke Mark, David Scott A., Fry Douglas Franklin, Hoekstra William J., Yates Christopher M.
Принадлежит:

The present invention relates to a process for preparing compound 1 that is useful as an antifungal agent. In particular, the invention seeks to provide new methodology for preparing compound 1 and substituted derivatives thereof. This application is a divisional of U.S. application Ser. No. 15/126,420 filed Sep. 15, 2016, which is the U.S. National Stage Application, pursuant to 35 U.S.C. § 371, of International Application No. PCT/US2015/021511, filed Mar. 19, 2015, which claims the benefit of U.S. Provisional Patent Application Ser. No. 61/955,650 filed Mar. 19, 2014, the entire disclosures of which are incorporated by reference herein.This invention was created in the performance of a Cooperative Research and Development Agreement with the National Institutes of Health, an Agency of the Department of Health and Human Services. The Government of the United States has certain rights in this invention.The present invention relates to a process for preparing compound 1 that is useful as an antifungal agent. In particular, the invention seeks to provide a new methodology for preparing compound 1 and substituted derivatives thereof.Living organisms have developed tightly regulated processes that specifically import metals, transport them to intracellular storage sites and ultimately transport them to sites of use. One of the most important functions of metals such as zinc and iron in biological systems is to enable the activity of metalloenzymes. Metalloenzymes are enzymes that incorporate metal ions into the enzyme active site and utilize the metal as a part of the catalytic process. More than one-third of all characterized enzymes are metalloenzymes.The function of metalloenzymes is highly dependent on the presence of the metal ion in the active site of the enzyme. It is well recognized that agents which bind to and inactivate the active site metal ion dramatically decrease the activity of the enzyme. Nature employs this same strategy to decrease the activity of ...

Подробнее
Номер записи: 100