title: Synthesis and SAR study of pyrrolo[3,4-b]pyridin-7(6H)-one derivatives as melanin concentrating hormone receptor 1 (MCH-R1) antagonists.
abstract: The discovery and optimization of novel pyrrolo[3,4-b]pyridin-7(6H)-one MCH-R1 antagonists are described. A systematic SAR study probing the effects of aryl-, benzyl- and arylthio-substituents at the 2-position of the pyrrolo[3,4-b]pyridin-7(6H)-ones led to identification of the 2-[(4-fluorophenyl)thio] derivative 7b as a highly potent MCH-R1 antagonist. This compound also has favorable pharmacokinetic properties along with a high metabolic stability and a minimal impact on CYP isoforms and hERG.
authors: Division of Drug Discovery Research, Korea Research Institute of Chemical Technology, Yuseong-gu, Daejeon 305-343, Republic of Korea.
authors: Chae Jo
authors: CJ
authors: Lim
authors: Ji Young
authors: JY
authors: Kim
authors: Byung Ho
authors: BH
authors: Lee
authors: Kwang-Seok
authors: KS
authors: Oh
authors: Kyu Yang
authors: KY
authors: Yi
mesh_terms: D000818:Animals; D019440:Anti-Obesity Agents / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000627:therapeutic use; D006207:Half-Life; D006801:Humans; D009765:Obesity / Q000188:drug therapy; D011485:Protein Binding; D011725:Pyridines / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D011743:Pyrimidines / Q000737:chemistry* / Q000378:metabolism / Q000493:pharmacokinetics; D011758:Pyrroles / Q000737:chemistry* / Q000378:metabolism / Q000493:pharmacokinetics; D011760:Pyrrolidinones / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D051381:Rats; D011979:Receptors, Pituitary Hormone / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D019440:Anti-Obesity Agents; D011725:Pyridines; D011743:Pyrimidines; D011758:Pyrroles; D011760:Pyrrolidinones; D011979:Receptors, Pituitary Hormone; C092274:melanin-concentrating hormone receptor; C527741:pyrrolopyrimidine