1-(4-Amino-phenyl)-pyrrolidin-3-yl-amine and 6-(3-amino-pyrrolidin-1-yl)-pyridin-3-yl-amine derivatives as melanin-concentrating hormone receptor-1 antagonists

Charles Q Huang; Tracy Baker; David Schwarz; Jun Fan; Christopher E Heise; Mingzhu Zhang; Val S Goodfellow; Stacy Markison; Kathleen R Gogas; Takung Chen; Xiao-Chuan Wang; Yun-Fei Zhu

doi:10.1016/j.bmcl.2005.05.130

1-(4-Amino-phenyl)-pyrrolidin-3-yl-amine and 6-(3-amino-pyrrolidin-1-yl)-pyridin-3-yl-amine derivatives as melanin-concentrating hormone receptor-1 antagonists

Bioorg Med Chem Lett. 2005 Aug 15;15(16):3701-6. doi: 10.1016/j.bmcl.2005.05.130.

Authors

Charles Q Huang¹, Tracy Baker, David Schwarz, Jun Fan, Christopher E Heise, Mingzhu Zhang, Val S Goodfellow, Stacy Markison, Kathleen R Gogas, Takung Chen, Xiao-Chuan Wang, Yun-Fei Zhu

Affiliation

¹ Department of Medicinal Chemistry, Neurocrine Biosciences, Inc., 12790 El Camino Real, San Diego, CA 92130, USA.

PMID: 16005225
DOI: 10.1016/j.bmcl.2005.05.130

Abstract

Derivatives of 1-(4-amino-phenyl)-pyrrolidin-3-yl-amine and 6-(3-amino-pyrrolidin-1-yl)-pyridin-3-yl-amine were identified as potent and functionally active MCH-R1 antagonists. One compound with Ki = 2.3 nM demonstrated good oral bioavailability (32%) and in vivo efficacy in rats.

MeSH terms

Administration, Oral
Animals
Biological Availability
Body Weight
Drug Evaluation, Preclinical
Humans
Male
Models, Animal
Molecular Structure
Pyridines / chemistry
Pyridines / pharmacokinetics
Pyridines / pharmacology*
Pyrrolidines / chemistry
Pyrrolidines / pharmacokinetics
Pyrrolidines / pharmacology*
Rats
Rats, Wistar
Receptors, Somatostatin / antagonists & inhibitors*
Receptors, Somatostatin / metabolism
Structure-Activity Relationship

Substances

MCHR1 protein, rat
Pyridines
Pyrrolidines
Receptors, Somatostatin