Potent 1,3,4-trisubstituted pyrrolidine CCR5 receptor antagonists: effects of fused heterocycles on antiviral activity and pharmacokinetic properties

Dooseop Kim; Liping Wang; Jeffrey J Hale; Christopher L Lynch; Richard J Budhu; Malcolm Maccoss; Sander G Mills; Lorraine Malkowitz; Sandra L Gould; Julie A DeMartino; Martin S Springer; Daria Hazuda; Michael Miller; Joseph Kessler; Renee C Hrin; Gwen Carver; Anthony Carella; Karen Henry; Janet Lineberger; William A Schleif; Emilio A Emini

doi:10.1016/j.bmcl.2005.02.030

Potent 1,3,4-trisubstituted pyrrolidine CCR5 receptor antagonists: effects of fused heterocycles on antiviral activity and pharmacokinetic properties

Bioorg Med Chem Lett. 2005 Apr 15;15(8):2129-34. doi: 10.1016/j.bmcl.2005.02.030.

Affiliation

¹ Department of Medicinal Chemistry, Merck Research Laboratories, RY800-206, PO Box 2000, Rahway, NJ 07065, USA. dooseop_kim@merck.com <dooseop_kim@merck.com>

PMID: 15808483
DOI: 10.1016/j.bmcl.2005.02.030

Abstract

A series of 1,3,4-trisubstituted pyrrolidine CCR5 receptor antagonists containing a variety of fused heterocycles at the 4-position of the piperidine side chain has been discovered, which are orally bioavailable with potent anti-HIV activity.

MeSH terms

Administration, Oral
Animals
Anti-HIV Agents / chemistry*
Anti-HIV Agents / pharmacokinetics
CCR5 Receptor Antagonists*
HeLa Cells
Heterocyclic Compounds / chemistry*
Heterocyclic Compounds / pharmacokinetics
Humans
Pyrrolidines / chemistry*
Pyrrolidines / pharmacokinetics
Rats
Receptors, CCR5 / metabolism

Substances

Anti-HIV Agents
CCR5 Receptor Antagonists
Heterocyclic Compounds
Pyrrolidines
Receptors, CCR5