1,3,4-Trisubstituted pyrrolidine CCR5 receptor antagonists. Part 1: discovery of the pyrrolidine scaffold and determination of its stereochemical requirements

• Published in: Bioorganic & medicinal chemistry letters Vol. 11; no. 11; pp. 1437 - 1440
• Main Authors: Hale, Jeffrey J., Budhu, Richard J., Mills, Sander G., MacCoss, Malcolm, Malkowitz, Lorraine, Siciliano, Salvatore, Gould, Sandra L., DeMartino, Julie A., Springer, Martin S.
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 04-06-2001; Elsevier
• Subjects: Animals; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antiviral agents; Binding, Competitive; Biological and medical sciences; CCR5 Receptor Antagonists; Chemokine CCL4; CHO Cells; Cricetinae; Iodine Radioisotopes; Macrophage Inflammatory Proteins - chemistry; Macrophage Inflammatory Proteins - pharmacology; Medical sciences; Molecular Conformation; Pharmacology. Drug treatments; Pyrrolidines - chemistry; Pyrrolidines - pharmacology; Receptors, CCR5 - genetics; Transfection; Sulfonamide; Sulfone; Nitrogen heterocycle; Retroviridae; Macrophage inflammatory protein 1alpha; Selectivity; Tricyclic compound; Lentivirus; In vitro; Pyrrolidine derivatives; Spiran; Virus; Chemokine; Stereoselectivity; Sulfur heterocycle; Structure activity relation; Sulfoxide; Affinity; Antiviral; Aromatic compound; Antagonist; Human immunodeficiency virus; Chemical synthesis; Biological receptor
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/S0960-894X(01)00232-3

A series of 1,3,4-trisubstituted pyrrolidines was discovered to have the ability to displace [
125I]-MIP-1α from the CCR5 receptor expressed on Chinese hamster ovary (CHO) cell membranes. CCR5 activity was found to be dependent on the regiochemistry and the absolute stereochemistry of the pyrrolidine.
A series of 1,3,4-trisubstituted pyrrolidines was discovered to have the ability to displace [
125I]-MIP-1α from the CCR5 receptor expressed on Chinese hamster ovary (CHO) cell membranes. CCR5 activity was found to be dependent on the regiochemistry and the absolute stereochemistry of the pyrrolidine.