Novel N-substituted benzimidazole CXCR4 antagonists as potential anti-HIV agents.
The lead optimization of a series of N-substituted benzimidazole CXCR4 antagonists is described. Side chain modifications and stereochemical optimization led to substantial improvements in potency and protein shift to afford compounds with low nanomolar anti-HIV activity.
Miller
John F
JF
Department of Medicinal Chemistry, Infectious Diseases Center for Excellence in Drug Discovery, GlaxoSmithKline Research and Development, Five Moore Drive, Research Triangle Park, NC 27709-3398, USA. john.6.miller@gsk.com
Turner
Elizabeth M
EM
Gudmundsson
Kristjan S
KS
Jenkinson
Stephen
S
Spaltenstein
Andrew
A
Thomson
Michael
M
Wheelan
Pat
P
D019380:Anti-HIV Agents / Q000737:chemistry* / Q000494:pharmacology*; D001562:Benzimidazoles / Q000737:chemistry* / Q000494:pharmacology*; D002460:Cell Line; D015658:HIV Infections / Q000188:drug therapy*; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D020128:Inhibitory Concentration 50; D019718:Receptors, CXCR4 / Q000037:antagonists & inhibitors* / Q000378:metabolism
D019380:Anti-HIV Agents; D001562:Benzimidazoles; D019718:Receptors, CXCR4