| Literature DB >> 19309152 |
Hong C Shen1, Fa-Xiang Ding, Qiaolin Deng, Larissa C Wilsie, Mihajlo L Krsmanovic, Andrew K Taggart, Ester Carballo-Jane, Ning Ren, Tian-Quan Cai, Tsuei-Ju Wu, Kenneth K Wu, Kang Cheng, Qing Chen, Michael S Wolff, Xinchun Tong, Tom G Holt, M Gerard Waters, Milton L Hammond, James R Tata, Steven L Colletti.
Abstract
Tricyclic analogues were rationally designed as the high affinity niacin receptor G-protein-coupled receptor 109A (GPR109A) agonists by overlapping three lead structures. Various tricyclic anthranilide and cycloalkene carboxylic acid full agonists were discovered with excellent in vitro activity. Compound 2g displayed a good therapeutic index regarding free fatty acids (FFA) reduction and vasodilation effects in rats, with very weak cytochrome P450 2C8 (CYP2C8) and cytochrome P450 2C9 (CYP2C9) inhibition, and a good mouse pharmacokinetics (PK) profile.Entities:
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Year: 2009 PMID： 19309152 DOI： 10.1021/jm900151e
Source DB: PubMed Journal: J Med Chem ISSN： 0022-2623 Impact factor: 7.446