Synthesis and structure-activity relationship of 7-azaindole piperidine derivatives as CCR2 antagonists

Mingde Xia; Cuifen Hou; Duane DeMong; Scott Pollack; Meng Pan; Monica Singer; Michele Matheis; William Murray; Druie Cavender; Michael Wachter

doi:10.1016/j.bmcl.2008.10.061

Synthesis and structure-activity relationship of 7-azaindole piperidine derivatives as CCR2 antagonists

Bioorg Med Chem Lett. 2008 Dec 15;18(24):6468-70. doi: 10.1016/j.bmcl.2008.10.061. Epub 2008 Oct 17.

Authors

Mingde Xia¹, Cuifen Hou, Duane DeMong, Scott Pollack, Meng Pan, Monica Singer, Michele Matheis, William Murray, Druie Cavender, Michael Wachter

Affiliation

¹ Drug Discovery, Johnson & Johnson Pharmaceutical Research and Development, L.L.C., 8 Clarke Drive, Cranbury, NJ 08512, USA. mxia@prdus.jnj.com

PMID: 18990568
DOI: 10.1016/j.bmcl.2008.10.061

Abstract

The synthesis and structure-activity relationship of a series of 7-azaindole piperidine derivatives are described. SAR studies led to the discovery of the potent CCR2 antagonists displaying IC(50) values in the nanomolar range. The representative compound 15 showed reasonable P450 and pharmacokinetics profile.

MeSH terms

Alcohols / chemistry
Binding Sites
Chemistry, Pharmaceutical / methods*
Chemokine CCL2 / chemistry*
Drug Design
Humans
Indoles / chemistry*
Inhibitory Concentration 50
Molecular Structure
Piperidines / chemistry*
Receptors, CCR2 / antagonists & inhibitors*
Receptors, CCR2 / chemistry*
Stereoisomerism
Structure-Activity Relationship

Substances

Alcohols
CCL2 protein, human
CCR2 protein, human
Chemokine CCL2
Indoles
Piperidines
Receptors, CCR2
piperidine