- Pyrido[1,2-a]pyrimidone analogs as PI3K inhibitors
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The present invention discloses a class of pyrido[1,2-a]pyrimidone analogs as PI3K inhibitors, and particularly relates to a compound represented by a formula (I) or a pharmaceutically acceptable salt thereof. The formula (I) is defined in the specification.
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Paragraph 0325; 0336; 0337; 0338
(2016/10/08)
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- Oxidative reaction of 2-aminopyridine-3-sulfonyl chlorides with tertiary amines
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2-Aminopyridine-3-sulfonyl chlorides undergo a reaction with tertiary amines in the presence of air to produce sulfonylethenamines. The 2-aminopyridine-3-sulfonyl chloride apparently plays a dual role in the process promoting the aerobic oxidation of the amine and electrophilically trapping the resulting enamine.
- Wei, Huiping,Wang, Gaigai,Li, Binbin,Huang, Jianjun,Li, Haiyan,Pereshivko, Olga P.,Peshkov, Vsevolod A.
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p. 333 - 337
(2016/12/16)
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- PERFORIN INHIBITING BENZENESULFONAMIDE COMPOUNDS, PREPARATION AND USES THEREOF
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Compounds of formula (la) and pharmaceutically acceptable salts, solvates, and hydrates thereof and related methods of modulatin perforin activity on a cell: wherein Ring A is selected from a 6-10 membered aryl, 5-6 membered cycloalkyi, 5-6 membered heteroaryl or 5-6 membered heterocyclyl, wherein the heteroaryl and heterocyclyl rings comprise at least one heteroatom selected from N, O or S; and wherein the aryl, cycloalkyi, heteroaryl or heterocyclyl rings are optionally substituted with 1 to 3 substituents selected from halo, nitro, -C1-Cealkyl, -C1-Ceaminoalkyl, -C1-C6hydroxyalkyl, -haloC1-C6alkyl, -C1- C6alkoxyl, -haloC1-C6alkyl, -CH2OC(O)CrC6alkyl, -C(O)OC1,-C6alkyI, -NHC(O)C1,-C6alkyl, -NHS(O)2C1- C6alkyl, -S(O)2C1-C6alkyl, -S(O)2NH2, and -C(O)NJJ; Ring B is a 6-10 membered arylene or a 5-6 membered heteroarylene comprising at least one heteroatom selected from N, 0 or S; and wherein the aryl or heteroaryl is optionally, substituted with one or more substituents selected from -NJJ, -OJ, halo,C1 -C6alkyl, -haloC1- C6alkyl, -C1-C6alkoxy, -haloC1-C6alkoxyl, and -C(0)NJJ; Ring C is is selected from a 5-10 membered heteroarylene or a 5-10 membered heterocyclene, each comprising at least one heteroatom selected from N, S and O; Ring D is an optionally substituted benzofused 9-11 membered heterocyclyl or optionally substituted ben2ofused 9-11 membered heteroaryl comprising at least one heteroatom selected from N or O; L is a linker selected from branched and unbranched C1-C4 alkylene, -S(0)2-NH-, -C(0)-NH-, -NH-C(0)-NH-, -S(0)2-NH-C(0)-NH-, -S(0)2-NH-C(0) - and -CH=CH-; wherein Rings B and C, and Rings C and D, are connected to each other via a C-C bond at any of the available C atoms on each respective ring; and J in each occurrence is independently selected from H, optionally substituted C1-C6alkyl or optionally substituted haloC1-C6alkyl.
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Page/Page column 98
(2014/03/25)
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- Synthesis and biological evaluation of 2-amino-5-aryl-3-benzylthiopyridine scaffold based potent c-Met inhibitors
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A series of 2-amino-N-benzylpyridine-3-carboxnamides, 2-amino-N- benzylpyridine-3-sulfonamides and 2-amino-3-benzylthiopyridines against c-Met were designed by means of bioisosteric replacement and docking analysis. Optimization of the 2-amino-3-benzylthiopyridine scaffold led to the identification of compound (R)-10b displaying c-Met inhibition with an IC 50 up to 7.7 nM. In the cytotoxic evaluation, compound (R)-10b effectively inhibited the proliferation of c-Met addictive human cancer cell lines (IC50 from 0.19 to 0.71 μM) and c-Met activation-mediated cell metastasis. At a dose of 100 mg/Kg, (R)-10b evidently inhibited tumor growth (45%) in NIH-3T3/TPR-Met xenograft model. Of note, (R)-10b could overcome c-Met-activation mediated gefitinib-resistance, which indicated its potential use for drug combination. Taken together, 2-amino-3-benzylthiopyridine scaffold was first disclosed and exhibited promising pharmacological profiles against c-Met, which left room for further exploration.
- Zhang, Dengyou,Zhang, Xiaowei,Ai, Jing,Zhai, Yun,Liang, Zhongjie,Wang, Ying,Chen, Yi,Li, Chunpu,Zhao, Fei,Jiang, Hualiang,Geng, Meiyu,Luo, Cheng,Liu, Hong
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p. 6804 - 6820
(2013/10/22)
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- Discovery of a novel series of potent and orally bioavailable phosphoinositide 3-kinase γ inhibitors
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The phosphoinositide 3-kinases (PI3Ks) have been linked to an extraordinarily diversified group of cellular functions making these enzymes compelling targets for the treatment of disease. A large body of evidence has linked PI3Kγ to the modulation of autoimmune and inflammatory processes making it an intriguing target for drug discovery. Our high-throughput screening (HTS) campaign revealed two hits that were nominated for further optimization studies. The in vitro activity of the first HTS hit, designated as the sulfonylpiperazine scaffold, was optimized utilizing structure-based design. However, nonoptimal pharmacokinetic properties precluded this series from further studies. An overlay of the X-ray structures of the sulfonylpiperazine scaffold and the second HTS hit within their complexes with PI3Kγ revealed a high degree of overlap. This feature was utilized to design a series of hybrid analogues including advanced leads such as 31 with desirable potency, selectivity, and oral bioavailability.
- Leahy, James W.,Buhr, Chris A.,Johnson, Henry W. B.,Kim, Byung Gyu,Baik, Taegon,Cannoy, Jonah,Forsyth, Timothy P.,Jeong, Joon Won,Lee, Matthew S.,Ma, Sunghoon,Noson, Kevin,Wang, Longcheng,Williams, Matthew,Nuss, John M.,Brooks, Eric,Foster, Paul,Goon, Leanne,Heald, Nathan,Holst, Charles,Jaeger, Christopher,Lam, Scott,Lougheed, Julie,Nguyen, Lam,Plonowski, Arthur,Song, Joanne,Stout, Thomas,Wu, Xiang,Yakes, Michael F.,Yu, Peiwen,Zhang, Wentao,Lamb, Peter,Raeber, Olivia
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experimental part
p. 5467 - 5482
(2012/09/25)
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- AMINOQUINOLINE DERIVATIVES AS ANTIVIRAL AGENTS
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Provided are compounds of Formula (I) and Formula (II) and pharmaceutically acceptable salts thereof, their pharmaceutical compositions, their methods of preparation, and their use for treating viral infections mediated by a member of the Flaviviridae family of viruses such as hepatitis C virus (HCV).
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Page/Page column 262
(2012/04/04)
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- QUINAZOLINES AS POTASSIUM ION CHANNEL INHIBITORS
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A compound of formula (I) wherein A, X, Y, Z, R1 and R24 are described herein. The compounds are useful as inhibitors of potassium channel function and in the treatment and prevention of arrhythmia, IKur-associated disorders, and other disorders mediated by ion channel function.
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Page/Page column 272
(2011/04/14)
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- Design and synthesis of potent and selective aldose reductase inhibitors based on pyridylthiadiazine scaffold
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A series of pyrido[2,3-e]-[1,2,4]-thiadiazine 1,1-dioxide acetic acid derivatives were synthesized and tested for their inhibitory activity against aldose reductase (ALR2). These derivatives were found to be potent aldose reductase inhibitors with IC
- Chen, Xin,Yang, Yanchun,Ma, Bing,Zhang, Shuzhen,He, Minlan,Gui, Dequan,Hussain, Saghir,Jing, Chaojun,Zhu, Changjin,Yu, Qun,Liu, Yan
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experimental part
p. 1536 - 1544
(2011/05/06)
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- QUINOXALINE DERIVATIVES AS PI3 KINASE INHIBITORS
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Invented is a method of inhibiting the activity/function of PI3 kinases using quinoxaline derivatives. Also invented is a method of treating one or more disease states selected from: autoimmune disorders, inflammatory diseases, cardiovascular diseases, neurodegenerative diseases, allergy, asthma, pancreatitis, multiorgan failure, kidney diseases, platelet aggregation, cancer, sperm motility, transplantation rejection, graft rejection and lung injuries by the administration of quinoxaline derivatives.
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Page/Page column 27; 85
(2009/01/20)
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- QUINAZOLINE DERIVATIVES AS PI3 KINASE INHIBITORS
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Invented is a method of inhibiting the activity/function of P13 kinases using quinazoline derivatives. Also invented is a method of treating one or more disease states selected from: autoimmune disorders, inflammatory diseases, cardiovascular diseases, neurodegenerative diseases, allergy, asthma, pancreatitis, multiorgan failure, kidney diseases, platelet aggregation, cancer, sperm motility, transplantation rejection, graft rejection and lung injuries by the administration of quinazoline derivatives.
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Page/Page column 74
(2009/01/23)
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- NAPHTHYRIDINE, DERIVATIVES AS P13 KINASE INHIBITORS
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Invented is a method of inhibiting the activity/function of PB kinases using naphthyridine derivatives. Also invented is a method of treating one or more disease states selected from: autoimmune disorders, inflammatory diseases, cardiovascular diseases, neurodegenerative diseases, allergy, asthma, pancreatitis, multiorgan failure, kidney diseases, platelet aggregation, cancer, sperm motility, transplantation rejection, graft rejection and lung injuries by the administration of naphthyridine derivatives.
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Page/Page column 53
(2009/01/24)
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- 5,6-DIHYDRO-1H-PYRIDIN-2-ONE COMPOUNDS
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The invention is directed to 5,6-dihydro-lH-pyridin-2-one compounds and pharmaceutical compositions containing such compounds that are useful in treating infections by hepatitis C virus.
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Page/Page column 218
(2008/12/04)
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