Design and synthesis of pseudo-symmetric HIV protease inhibitors containing a novel hydroxymethylcarbonyl (HMC)-hydrazide isostere.
Pseudo-symmetric HIV-1 protease inhibitors containing a novel HMC-hydrazide isostere as the transition-state mimic were designed and synthesized. Most of the synthetic compounds with varied structures at the P and P' sites around this core unit showed potent inhibitory activity against HIV-1 protease with nanomolar K(i) values.
Hidaka
Koushi
K
Department of Medicinal Chemistry, Center of Frontier Reseach in Medicinal Science, Kyoto Pharmaceutical University, Yamashina-ku, Japan.
Kimura
Tooru
T
Hayashi
Yoshio
Y
McDaniel
Keith F
KF
Dekhtyar
Tatyana
T
Colletti
Lynn
L
Kiso
Yoshiaki
Y
D015195:Drug Design; D016333:HIV Protease / Q000187:drug effects; D017320:HIV Protease Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D006801:Humans; D006834:Hydrazines / Q000737:chemistry*; D020128:Inhibitory Concentration 50; D018716:Molecular Mimicry; D009842:Oligopeptides / Q000138:chemical synthesis* / Q000494:pharmacology; D013329:Structure-Activity Relationship
D017320:HIV Protease Inhibitors; D006834:Hydrazines; D009842:Oligopeptides; C029424:hydrazine; D016333:HIV Protease