3-Amino-1-alkyl-cyclopentane carboxamides as small molecule antagonists of the human and murine CC chemokine receptor 2

Gabor Butora; Richard Jiao; William H Parsons; Pasquale P Vicario; Hong Jin; Julia M Ayala; Margaret A Cascieri; Lihu Yang

doi:10.1016/j.bmcl.2007.04.053

3-Amino-1-alkyl-cyclopentane carboxamides as small molecule antagonists of the human and murine CC chemokine receptor 2

Bioorg Med Chem Lett. 2007 Jul 1;17(13):3636-41. doi: 10.1016/j.bmcl.2007.04.053. Epub 2007 Apr 25.

Authors

Gabor Butora¹, Richard Jiao, William H Parsons, Pasquale P Vicario, Hong Jin, Julia M Ayala, Margaret A Cascieri, Lihu Yang

Affiliation

¹ Merck Research Laboratories, Rahway, NJ 07065, USA. gabor_butora@merck.com <gabor_butora@merck.com>

PMID: 17482462
DOI: 10.1016/j.bmcl.2007.04.053

Abstract

A series of low molecular weight antagonists of both the human and murine CC chemokine receptor 2, containing a 1-alkyl-3-(3-methyl-4-spiroindenylpiperidine)-substituted cyclopentanecarboxamide, is described. A SAR study of the C(1) substituent revealed that short, branched alkyl groups such as isopropyl, isobutyl, or cyclopropyl are optimal for both human and murine CCR2 binding activity.

MeSH terms

Amides / chemical synthesis*
Amides / chemistry*
Animals
Carbon / chemistry*
Chemistry, Pharmaceutical / methods*
Cyclopentanes / chemical synthesis*
Cyclopentanes / chemistry*
Drug Design
Humans
Inhibitory Concentration 50
Leukocytes / metabolism
Male
Mice
Molecular Weight
Rats
Rats, Sprague-Dawley
Receptors, CCR2
Receptors, Chemokine / antagonists & inhibitors*
Receptors, Chemokine / metabolism*
Structure-Activity Relationship

Substances

Amides
CCR2 protein, human
Ccr2 protein, mouse
Ccr2 protein, rat
Cyclopentanes
Receptors, CCR2
Receptors, Chemokine
cyclopentane dicarboxamide
Carbon