CCR5 receptor antagonists: discovery and SAR study of guanylhydrazone derivatives.
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.
Wei
Robert G
RG
Berlex Biosciences, 2600 Hilltop Drive, Richmond, CA 94804, USA.
Arnaiz
Damian O
DO
Chou
Yuo-Ling
YL
Davey
Dave
D
Dunning
Laura
L
Lee
Wheeseong
W
Lu
Shou-Fu
SF
Onuffer
James
J
Ye
Bin
B
Phillips
Gary
G
D019380:Anti-HIV Agents / Q000138:chemical synthesis / Q000737:chemistry*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000138:chemical synthesis / Q000737:chemistry*; D065100:CCR5 Receptor Antagonists; D002478:Cells, Cultured; D004353:Drug Evaluation, Preclinical; D006801:Humans; D020128:Inhibitory Concentration 50; D008935:Mitoguazone / Q000031:analogs & derivatives*; D013329:Structure-Activity Relationship
D019380:Anti-HIV Agents; D000894:Anti-Inflammatory Agents, Non-Steroidal; D065100:CCR5 Receptor Antagonists; D008935:Mitoguazone