Synthesis and SAR investigations of novel 2-arylbenzimidazole derivatives as melanin-concentrating hormone receptor 1 (MCH-R1) antagonists

Chae Jo Lim; Nakjeong Kim; Eun Kyoung Lee; Byung Ho Lee; Kwang-Seok Oh; Sung-eun Yoo; Kyu Yang Yi

doi:10.1016/j.bmcl.2011.02.099

Synthesis and SAR investigations of novel 2-arylbenzimidazole derivatives as melanin-concentrating hormone receptor 1 (MCH-R1) antagonists

Bioorg Med Chem Lett. 2011 Apr 15;21(8):2309-12. doi: 10.1016/j.bmcl.2011.02.099. Epub 2011 Feb 26.

Authors

Chae Jo Lim¹, Nakjeong Kim, Eun Kyoung Lee, Byung Ho Lee, Kwang-Seok Oh, Sung-eun Yoo, Kyu Yang Yi

Affiliation

¹ Bio-organic Science Division, Korea Research Institute of Chemical Technology, Yuseong-gu, Daejeon 305-600, Republic of Korea.

PMID: 21420863
DOI: 10.1016/j.bmcl.2011.02.099

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Acetanilides / chemical synthesis*
Acetanilides / chemistry
Acetanilides / pharmacokinetics
Administration, Oral
Animals
Benzimidazoles / chemical synthesis*
Benzimidazoles / chemistry
Benzimidazoles / pharmacokinetics
Brain / metabolism
Humans
Rats
Receptors, Somatostatin / antagonists & inhibitors*
Receptors, Somatostatin / metabolism
Structure-Activity Relationship

Substances

Acetanilides
Benzimidazoles
MCHR1 protein, human
Receptors, Somatostatin