title: Synthesis and SAR investigations of novel 2-arylbenzimidazole derivatives as melanin-concentrating hormone receptor 1 (MCH-R1) antagonists.
abstract: Compounds containing 2-arybenzimidazole ring systems linked to arylpiperidines were synthesized and evaluated as MCH-R1 antagonists. The results of structure-activity relationship studies led to the identification of compound 4c as a potent MCH-R1 antagonist (IC(50)=1 nM). This compound also has good metabolic stability, and favorable pharmacokinetic and brain penetration properties. However 4c was found to be potent inhibitor of the hERG potassium channel.
authors.affiliation: Bio-organic Science Division, Korea Research Institute of Chemical Technology, Yuseong-gu, Daejeon 305-600, Republic of Korea.
authors.forename: Chae Jo
authors.initials: CJ
authors.lastname: Lim
authors.forename: Nakjeong
authors.initials: N
authors.lastname: Kim
authors.forename: Eun Kyoung
authors.initials: EK
authors.lastname: Lee
authors.forename: Byung Ho
authors.initials: BH
authors.lastname: Lee
authors.forename: Kwang-Seok
authors.initials: KS
authors.lastname: Oh
authors.forename: Sung-eun
authors.initials: SE
authors.lastname: Yoo
authors.forename: Kyu Yang
authors.initials: KY
authors.lastname: Yi
mesh_terms: D000083:Acetanilides / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D000284:Administration, Oral; D000818:Animals; D001562:Benzimidazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D001921:Brain / Q000378:metabolism; D006801:Humans; D051381:Rats; D017481:Receptors, Somatostatin / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D000083:Acetanilides; D001562:Benzimidazoles; C103263:MCHR1 protein, human; D017481:Receptors, Somatostatin