Design and synthesis of novel HIV-1 protease inhibitors incorporating oxyindoles as the P2'-ligands.
A series of novel oxyindole-derived HIV-1 protease inhibitors were designed and synthesized based upon our X-ray crystal structure of inhibitor 2 (TMC-114) bound to HIV-1 protease. The effects of substituents, spirocyclic rings, and ring sizes have been investigated. A number of inhibitors exhibited low nanomolar inhibitory potencies against HIV protease.
Ghosh
Arun K
AK
Department of Chemistry, Purdue University, West Lafayette, IN 47907, USA. akghosh@purdue.edu
Schiltz
Gary
G
Perali
Ramu Sridhar
RS
Leshchenko
Sofiya
S
Kay
Stephanie
S
Walters
D Eric
DE
Koh
Yasuhiro
Y
Maeda
Kenji
K
Mitsuya
Hiroaki
H
D002460:Cell Line; D018360:Crystallography, X-Ray; D015195:Drug Design; D017320:HIV Protease Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology; D015497:HIV-1 / Q000187:drug effects*; D007211:Indoles / Q000737:chemistry*; D008024:Ligands; D008958:Models, Molecular
D017320:HIV Protease Inhibitors; D007211:Indoles; D008024:Ligands