1236357-70-2Relevant academic research and scientific papers
Defining the key pharmacophore elements of PF-04620110: Discovery of a potent, orally-active, neutral DGAT-1 inhibitor
Dow, Robert L.,Andrews, Melissa P.,Li, Jian-Cheng,Michael Gibbs,Guzman-Perez, Angel,Laperle, Jennifer L.,Li, Qifang,Mather, Dawn,Munchhof, Michael J.,Niosi, Mark,Patel, Leena,Perreault, Christian,Tapley, Susan,Zavadoski, William J.
, p. 5081 - 5097 (2013/09/02)
DGAT-1 is an enzyme that catalyzes the final step in triglyceride synthesis. mRNA knockout experiments in rodent models suggest that inhibitors of this enzyme could be of value in the treatment of obesity and type II diabetes. The carboxylic acid-based DGAT-1 inhibitor 1 was advanced to clinical trials for the treatment of type 2 diabetes, despite of the low passive permeability of 1. Because of questions relating to the potential attenuation of distribution and efficacy of a poorly permeable agent, efforts were initiated to identify compounds with improved permeability. Replacement of the acid moiety in 1 with an oxadiazole led to the discovery of 52, which possesses substantially improved passive permeability. The resulting pharmacodynamic profile of this neutral DGAT-1 inhibitor was found to be similar to 1 at comparable plasma exposures.
4-AMINO-5-OXO-7, 8-DIHYDROPYRIMIDO [5,4-F] [1,4] OXAZEPIN-6 (5H) -YL) PHENYL DERIVATIVES, PHARMACEUTICAL COMPOSITIONS AND USES THEREOF
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Page/Page column 79-80, (2010/08/09)
The invention provides compounds of Formula (I), wherein R1, R2a, R2b, R3, m and A are as defined herein, as well as compositions thereof and methods for treating a disease, condition or disorder that is modulated by the inhibition of the diacylglycerol O-acyltransferase 1 (DGAT-1) enzyme by administering the compounds of the present invention and/or compositions thereof.
