Design and synthesis of novel small molecule CCR2 antagonists: evaluation of 4-aminopiperidine derivatives

M Vilums; A J M Zweemer; S Dekkers; Y Askar; H de Vries; J Saunders; D Stamos; J Brussee; L H Heitman; A P IJzerman

doi:10.1016/j.bmcl.2014.10.060

Design and synthesis of novel small molecule CCR2 antagonists: evaluation of 4-aminopiperidine derivatives

Bioorg Med Chem Lett. 2014 Dec 1;24(23):5377-80. doi: 10.1016/j.bmcl.2014.10.060.

Authors

M Vilums, A J M Zweemer, S Dekkers, Y Askar, H de Vries, J Saunders, D Stamos, J Brussee, L H Heitman, A P IJzerman

PMID: 25453791
DOI: 10.1016/j.bmcl.2014.10.060

Abstract

A novel N-(2-oxo-2-(piperidin-4-ylamino)ethyl)-3-(trifluoromethyl)benzamide series of human CCR2 chemokine receptor antagonists was identified. With a pharmacophore model based on known CCR2 antagonists a new core scaffold was designed, analogues of it synthesized and structure–affinity relationship studies derived yielding a new high affinity CCR2 antagonist N-(2-((1-(4-(3-methoxyphenyl)cyclohexyl)piperidin-4-yl)amino)-2-oxoethyl)-3-(trifluoromethyl)benzamide.

Publication types

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

MeSH terms

Chemokines
Humans
Molecular Structure
Piperidines / chemistry*
Receptors, CCR2 / antagonists & inhibitors*
Receptors, CCR2 / chemistry
Structure-Activity Relationship

Substances

4-aminopiperidine
Chemokines
Piperidines
Receptors, CCR2