94856-52-7Relevant academic research and scientific papers
Discovery and optimization of quinolinone derivatives as potent, selective, and orally bioavailable mutant isocitrate dehydrogenase 1 (mIDH1) inhibitors
Lin, Jian,Lu, Wei,Caravella, Justin A.,Campbell, Ann Marie,Diebold, R. Bruce,Ericsson, Anna,Fritzen, Edward,Gustafson, Gary R.,Lancia, David R.,Shelekhin, Tatiana,Wang, Zhongguo,Castro, Jennifer,Clarke, Andrea,Gotur, Deepali,Josephine, Helen R.,Katz, Marie,Diep, Hien,Kershaw, Mark,Yao, Lili,Kauffman, Goss,Hubbs, Stephen E.,Luke, George P.,Toms, Angela V.,Wang, Liann,Bair, Kenneth W.,Barr, Kenneth J.,Dinsmore, Christopher,Walker, Duncan,Ashwell, Susan
, p. 6575 - 6596 (2019/08/20)
Mutations at the arginine residue (R132) in isocitrate dehydrogenase 1 (IDH1) are frequently identified in various human cancers. Inhibition of mutant IDH1 (mIDH1) with small molecules has been clinically validated as a promising therapeutic treatment for acute myeloid leukemia and multiple solid tumors. Herein, we report the discovery and optimization of a series of quinolinones to provide potent and orally bioavailable mIDH1 inhibitors with selectivity over wild-type IDH1. The X-ray structure of an early lead 24 in complex with mIDH1-R132H shows that the inhibitor unexpectedly binds to an allosteric site. Efforts to improve the in vitro and in vivo absorption, distribution, metabolism, and excretion (ADME) properties of 24 yielded a preclinical candidate 63. The detailed preclinical ADME and pharmacology studies of 63 support further development of quinolinone-based mIDH1 inhibitors as therapeutic agents in human trials.
QUINOLINONE PYRIMIDINES COMPOSITIONS AS MUTANT-ISOCITRATE DEHYDROGENASE INHIBITORS
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Paragraph 0951; 0952; 0953, (2016/04/19)
The invention relates to inhibitors of mutant isocitrate dehydrogenase (mt-IDH) proteins with neomorphic activity useful in the treatment of cell-proliferation disorders and cancers, having the Formula: where A, B, W1, W2, W3, and R1-R6 are described herein.
QUINAZOLINE BASED RESPIRATORY SYNCYTIAL VIRUS INHIBITORS
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Page/Page column 58, (2015/05/19)
Compounds of Formula (I), wherein R1, R2, R3, R4 and n are defined herein, are useful as inhibitors of RSV.
Copper-Catalyzed N- and O-arylation of amides: Alternative approaches to 3,4-dihydroquinolin-2-ones, quinolin-2-ones, and 12h-chromeno[2,3-b]quinolin-12- ones
Zhang, Xinying,Guo, Xiaojie,Fang, Liangliang,Song, Yunping,Fan, Xuesen
, p. 8087 - 8093 (2014/01/06)
The efficient syntheses of 3-cyanoquinolin-2-ones, 3-(2-bromobenzyl)-3- cyano-3,4-dihydroquinolin-2-ones, 3-(2-bromobenzyl)quinolin-2-ones, and 12H-chromeno[2,3-b]quinolin-12-ones through copper-catalyzed N- and O-arylation of amides by using readily avai
(1H-tetrazol-5-yl)-2(1H)-quinolinones and-naphthyridones and antiallergic use thereof
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, (2008/06/13)
(1H-Tetrazol-5-yl)-2(1H)-quinolones useful as antiallergic agents are described herein. The compounds are prepared by the reaction of sodium azide and ammonium chloride with an appropriate 3-cyano-2(1H)-quinolinone.
