CCR5 receptor antagonists: Discovery and SAR study of guanylhydrazone derivatives

• Published in: Bioorganic & medicinal chemistry letters Vol. 17; no. 1; pp. 231 - 234
• Main Authors: Wei, Robert G., Arnaiz, Damian O., Chou, Yuo-Ling, Davey, Dave, Dunning, Laura, Lee, Wheeseong, Lu, Shou-Fu, Onuffer, James, Ye, Bin, Phillips, Gary
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 2007
• Subjects: Anti-HIV Agents - chemical synthesis; Anti-HIV Agents - chemistry; Anti-Inflammatory Agents, Non-Steroidal - chemical synthesis; Anti-Inflammatory Agents, Non-Steroidal - chemistry; CCR5; CCR5 Receptor Antagonists; Cells, Cultured; Chemokine receptor antagonists; Drug Evaluation, Preclinical; Humans; Inhibitory Concentration 50; Mitoguazone - analogs & derivatives; Structure-Activity Relationship; CCR5; Chemokine receptor antagonists
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2006.09.052

High throughput screening (HTS) led to the identification of the guanylhydrazone of 2-(4-chlorobenzyloxy)-5-bromobenzaldehyde as a CCR5 receptor antagonist. Modifications of the guanylhydrazone resulted in the discovery of novel CCR5 antagonists. High throughput screening (HTS) led to the identification of the guanylhydrazone of 2-(4-chlorobenzyloxy)-5-bromobenzaldehyde as a CCR5 receptor antagonist. Initial modifications of the guanylhydrazone series indicated that substitution of the benzyl group at the para-position was well tolerated. Substitution at the 5-position of the central phenyl ring was critical for potency. Replacement of the guanylhydrazone group led to the discovery of a novel series of CCR5 antagonists.