Evaluation of secondary amide replacements in a series of CCR5 antagonists as a means to increase intrinsic membrane permeability. Part 1: Optimization of gem-disubstituted azacycles

Rémy C Lemoine; Ann C Petersen; Lina Setti; Jutta Wanner; Andreas Jekle; Gabrielle Heilek; André deRosier; Changhua Ji; Pamela Berry; David Rotstein

doi:10.1016/j.bmcl.2009.11.072

Evaluation of secondary amide replacements in a series of CCR5 antagonists as a means to increase intrinsic membrane permeability. Part 1: Optimization of gem-disubstituted azacycles

Bioorg Med Chem Lett. 2010 Jan 15;20(2):704-8. doi: 10.1016/j.bmcl.2009.11.072. Epub 2009 Dec 7.

Authors

Rémy C Lemoine¹, Ann C Petersen, Lina Setti, Jutta Wanner, Andreas Jekle, Gabrielle Heilek, André deRosier, Changhua Ji, Pamela Berry, David Rotstein

Affiliation

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

PMID: 20004099
DOI: 10.1016/j.bmcl.2009.11.072

Abstract

Replacement of a secondary amide with an N-acyl or N-sulfonyl gem-disubstituted azacyle in a series of CCR5 antagonists led to the identification of compounds with excellent in vitro HIV antiviral activity and increased intrinsic membrane permeability.

MeSH terms

Amides / chemistry*
Anti-HIV Agents / chemical synthesis
Anti-HIV Agents / chemistry*
Anti-HIV Agents / pharmacology
Aza Compounds / chemical synthesis
Aza Compounds / chemistry*
Aza Compounds / pharmacology
CCR5 Receptor Antagonists*
Cell Line, Tumor
Cell Membrane Permeability / drug effects
HIV Fusion Inhibitors / chemical synthesis
HIV Fusion Inhibitors / chemistry*
HIV Fusion Inhibitors / pharmacology
Humans
Receptors, CCR5 / metabolism

Substances

Amides
Anti-HIV Agents
Aza Compounds
CCR5 Receptor Antagonists
HIV Fusion Inhibitors
Receptors, CCR5