915948-98-0Relevant articles and documents
Discovery of a Partial Glucokinase Activator Clinical Candidate: Diethyl ((3-(3-((5-(Azetidine-1-carbonyl)pyrazin-2-yl)oxy)-5-isopropoxybenzamido)-1H-pyrazol-1-yl)methyl)phosphonate (BMS-820132)
Barrish, Joel C.,Behnia, Kamelia,Bolton, Scott,Brigance, Robert P.,Cap, Michael,Chen, Bang-Chi,Chen, Sean,Chen, Xue-Qing,Cheng, Peter T. W.,Ellsworth, Bruce,Everlof, Gerry,Fuentes-Catanio, Helen G.,Fura, Aberra,Griffen, Steven,Gupta, Anuradha,Janovitz, Evan B.,Jones, Beverly,Kalinowski, Stephen,Kirby, Mark,Kopcho, Lisa,Krupinski, John,Krystek, Stanley R.,Kunselman, Lori,Langish, Robert A.,Leith, Leslie W.,Li, Yi-Xin,Liu, Heng,Ma, Xiaohui,Marcinkeviciene, Jovita,Mathur, Arvind,Meng, Wei,Muckelbauer, Jodi K.,Nielsen, Laura,O'Malley, Kevin,Pannacciulli, Nicola,Rampulla, Richard,Robl, Jeffrey A.,Ryono, Denis E.,Shi, Yan,Smirk, Rebecca,Spronk, Steven A.,Staal, Ada,Sulsky, Richard,Sun, Dawn,Sun, Jung-Hui,Swartz, Joann,Tao, Shiwei,Taylor, Joseph R.,Tino, Joseph A.,Wang, Aiying,Wang, Qi,Wang, Ying,Whaley, Jean,Williams, Kristin N.,Wong, Michael K. Y.,Wu, Dauh-Rurng,Xu, Carrie,Yang, Yanou,Zahler, Robert,Zalaznick, Jacob,Zebo, Rachel,Zhang, Hao,Zinker, Bradley A.
, p. 4291 - 4317 (2022/03/02)
Glucokinase (GK) is a key regulator of glucose homeostasis, and its small-molecule activators represent a promising opportunity for the treatment of type 2 diabetes. Several GK activators have been advanced into clinical trials and have demonstrated promising efficacy; however, hypoglycemia represents a key risk for this mechanism. In an effort to mitigate this hypoglycemia risk while maintaining the efficacy of the GK mechanism, we have investigated a series of amino heteroaryl phosphonate benzamides as ‘‘partial” GK activators. The structure-activity relationship studies starting from a “full GK activator” 11, which culminated in the discovery of the “partial GK activator” 31 (BMS-820132), are discussed. The synthesis and in vitro and in vivo preclinical pharmacology profiles of 31 and its pharmacokinetics (PK) are described. Based on its promising in vivo efficacy and preclinical ADME and safety profiles, 31 was advanced into human clinical trials.
2-(3,5-DISUBSTITUTEDPHENYL)PYRIMIDIN-4(3H)-ONE DERIVATIVES
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Page/Page column 37, (2012/01/06)
O N NH R3 R2 O R1 168 ABSTRACT The present invention provides a 2-(3,5-disubstitutedphenyl)pyrimidin- 4(3H)-one compound of Formula (I) 5 (I) or a pharmaceutically acceptable salt thereof wherein R 1, R2 and R3 are as defined herein. The compounds of Formula (I) have been found to act as glucokinase activators. Consequently, the compounds of Formula (I) and 10 the pharmaceutical compositions thereof are useful for the treatment of diseases, disorders, or conditions mediated by glucokinase.
CHEMICAL PROCESS 632
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Page/Page column 18-19, (2010/08/22)
A process for preparing pharmaceutically active compounds of formula (I) or a salt thereof wherein R1, n, m, R3, R6, X1, X2, X3 and X4 are as defined in the specification, is described. Novel intermediates are also described and claimed.
