Discovery and characterization of a potent and selective antagonist of melanin-concentrating hormone receptor 2

Xiaoqi Chen; Jeff Mihalic; Pingchen Fan; Lingming Liang; Michelle Lindstrom; Sylvia Wong; Qiuping Ye; Ying Fu; Juan Jaen; Jin-Long Chen; Kang Dai; Leping Li

doi:10.1016/j.bmcl.2011.10.125

Discovery and characterization of a potent and selective antagonist of melanin-concentrating hormone receptor 2

Bioorg Med Chem Lett. 2012 Jan 1;22(1):363-6. doi: 10.1016/j.bmcl.2011.10.125. Epub 2011 Nov 9.

Authors

Xiaoqi Chen¹, Jeff Mihalic, Pingchen Fan, Lingming Liang, Michelle Lindstrom, Sylvia Wong, Qiuping Ye, Ying Fu, Juan Jaen, Jin-Long Chen, Kang Dai, Leping Li

Affiliation

¹ Amgen Inc., 1120 Veterans Boulevard, ASF2-3, South San Francisco, CA 94080, USA. [email protected]

PMID: 22123324
DOI: 10.1016/j.bmcl.2011.10.125

Abstract

A series of spiropiperidine carbazoles were synthesized and evaluated as MCHR2 antagonists using a FLIPR assay. The pharmacokinetic properties of selected compounds have also been studied. This effort led to the discovery of potent and specific MCHR2 antagonists. Compound 38 demonstrated good pharmacokinetic properties across rat, beagle dog and rhesus monkey and had a favorable selectivity profile against a number of other receptors. These MCHR2 antagonists are considered appropriate tool compounds for study of the function of MCHR2 in vivo.

MeSH terms

Animals
CHO Cells
Carbazoles / chemistry*
Cell Line
Chemistry, Pharmaceutical / methods*
Cricetinae
Dogs
Drug Design
Humans
Inhibitory Concentration 50
Macaca mulatta
Models, Chemical
Piperidines / chemistry*
Rats
Receptors, G-Protein-Coupled / antagonists & inhibitors*
Receptors, Pituitary Hormone / antagonists & inhibitors*
Structure-Activity Relationship

Substances

Carbazoles
MCHR2 protein, human
Piperidines
Receptors, G-Protein-Coupled
Receptors, Pituitary Hormone