Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
, 52 (8), 2587-602

Discovery of Novel Tricyclic Full Agonists for the G-protein-coupled Niacin Receptor 109A With Minimized Flushing in Rats

Affiliations

Discovery of Novel Tricyclic Full Agonists for the G-protein-coupled Niacin Receptor 109A With Minimized Flushing in Rats

Hong C Shen et al. J Med Chem.

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.

Similar articles

See all similar articles

Cited by 6 articles

See all "Cited by" articles

MeSH terms

LinkOut - more resources

Feedback