1,3,4-Trisubstituted pyrrolidine CCR5 receptor antagonists. Part 3: Polar functionality and its effect on anti-HIV-1 activity

• Published in: Bioorganic & medicinal chemistry letters Vol. 12; no. 20; pp. 2997 - 3000
• Main Authors: HALE, Jeffrey J, BUDHU, Richard J, HAZUDA, Daria, MILLER, Michael, KESSLER, Joseph, DANZEISEN, Renee, HOLMES, Karen, LINEBERGER, Janet, CARELLA, Anthony, CARVER, Gwen, EMINI, Emilio A, MILLS, Sander G, MACCOSS, Malcolm, GOULD, Sandra L, DEMARTINO, Julie A, SPRINGER, Martin S, SICILIANO, Salvatore J, MALKOWITZ, Lorraine, SCHLEIF, William A
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier 21-10-2002
• Subjects: Animals; Anti-HIV Agents - chemical synthesis; Anti-HIV Agents - pharmacokinetics; Anti-HIV Agents - pharmacology; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antiviral agents; Biological and medical sciences; Calcium Channels, L-Type - drug effects; CCR5 Receptor Antagonists; Chemical Phenomena; Chemistry, Physical; Chemokine CCL4; CHO Cells; Cricetinae; Half-Life; HeLa Cells; HIV-1 - drug effects; Humans; Macrophage Inflammatory Proteins - antagonists & inhibitors; Medical sciences; Pharmacology. Drug treatments; Rats; Receptors, CCR5 - chemistry; Structure-Activity Relationship; Tetrazole derivatives; Aminoalcohol; Cyclohexane derivatives; HIV-1 virus; Nitrogen heterocycle; Benzene derivatives; Retroviridae; Selectivity; Lentivirus; In vitro; Pyrrolidine derivatives; Virus; CCR5 chemokine receptor; Structure activity relation; Affinity; Antiviral; Human immunodeficiency virus; Antagonist; Chemical synthesis
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/S0960-894X(02)00605-4

Incorporation of acidic functional groups into a lead CCR5 antagonist identified from a targeted combinatorial library resulted in compounds with enhanced anti-HIV-1 activity and attenuated L-type calcium channel affinity.