Evaluation of amide replacements in CCR5 antagonists as a means to increase intrinsic permeability. Part 2: SAR optimization and pharmacokinetic profile of a homologous azacyle series

Jutta Wanner; Lijing Chen; Rémy C Lemoine; Rama Kondru; Andreas Jekle; Gabrielle Heilek; André deRosier; Changhua Ji; Pamela W Berry; David M Rotstein

doi:10.1016/j.bmcl.2010.08.118

Evaluation of amide replacements in CCR5 antagonists as a means to increase intrinsic permeability. Part 2: SAR optimization and pharmacokinetic profile of a homologous azacyle series

Bioorg Med Chem Lett. 2010 Nov 15;20(22):6802-7. doi: 10.1016/j.bmcl.2010.08.118. Epub 2010 Sep 18.

Authors

Jutta Wanner¹, Lijing Chen, Rémy C Lemoine, Rama Kondru, Andreas Jekle, Gabrielle Heilek, André deRosier, Changhua Ji, Pamela W Berry, David M Rotstein

Affiliation

¹ Department of Medicinal Chemistry, Roche Palo Alto, 3431 Hillview Avenue, Palo Alto, CA 94304, USA. [email protected]

PMID: 20855212
DOI: 10.1016/j.bmcl.2010.08.118

Abstract

Replacement of a secondary amide with a piperidine or azetidine moiety in a series of CCR5 antagonists led to the discovery of compounds with increased intrinsic permeability. This effort led to the identification of a potent CCR5 antagonist which exhibited an improved in vivo pharmacokinetic profile.

MeSH terms

Amides / chemistry*
Aza Compounds / chemistry
Aza Compounds / pharmacokinetics
Aza Compounds / pharmacology*
CCR5 Receptor Antagonists*
Structure-Activity Relationship

Substances

Amides
Aza Compounds
CCR5 Receptor Antagonists