1,3,4-Trisubstituted pyrrolidine CCR5 receptor antagonists. Part 2: lead optimization affording selective, orally bioavailable compounds with potent anti-HIV activity

J J Hale; R J Budhu; E B Holson; P E Finke; B Oates; S G Mills; M MacCoss; S L Gould; J A DeMartino; M S Springer; S Siciliano; L Malkowitz; W A Schleif; D Hazuda; M Miller; J Kessler; R Danzeisen; K Holmes; J Lineberger; A Carella; G Carver; E Emini

doi:10.1016/s0960-894x(01)00545-5

1,3,4-Trisubstituted pyrrolidine CCR5 receptor antagonists. Part 2: lead optimization affording selective, orally bioavailable compounds with potent anti-HIV activity

Bioorg Med Chem Lett. 2001 Oct 22;11(20):2741-5. doi: 10.1016/s0960-894x(01)00545-5.

Affiliation

¹ Department of Medicinal Chemistry, Merck Research Laboratories, Rahway, NJ 07065, USA. jeffrey_hale@merck.com

PMID: 11591514
DOI: 10.1016/s0960-894x(01)00545-5

Abstract

Investigations of the structure-activity relationships of 1,3,4-trisubstituted pyrrolidine human CCR5 receptor antagonists afforded orally bioavailable compounds with the ability to inhibit HIV replication in vitro.

MeSH terms

Administration, Oral
Animals
Anti-HIV Agents / chemical synthesis
Anti-HIV Agents / chemistry
Anti-HIV Agents / pharmacokinetics
Anti-HIV Agents / pharmacology*
Biological Availability
CCR5 Receptor Antagonists*
CHO Cells
Cricetinae
HIV / drug effects*
HeLa Cells
Humans
Microbial Sensitivity Tests
Pyrrolidines / chemical synthesis
Pyrrolidines / chemistry
Pyrrolidines / pharmacokinetics
Pyrrolidines / pharmacology*
Structure-Activity Relationship

Substances

Anti-HIV Agents
CCR5 Receptor Antagonists
Pyrrolidines