title: Design and synthesis of pseudo-symmetric HIV protease inhibitors containing a novel hydroxymethylcarbonyl (HMC)-hydrazide isostere.
abstract: 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.
authors.affiliation: Department of Medicinal Chemistry, Center of Frontier Reseach in Medicinal Science, Kyoto Pharmaceutical University, Yamashina-ku, Japan.
authors.forename: Koushi
authors.initials: K
authors.lastname: Hidaka
authors.forename: Tooru
authors.initials: T
authors.lastname: Kimura
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Hayashi
authors.forename: Keith F
authors.initials: KF
authors.lastname: McDaniel
authors.forename: Tatyana
authors.initials: T
authors.lastname: Dekhtyar
authors.forename: Lynn
authors.initials: L
authors.lastname: Colletti
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Kiso
mesh_terms: 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
chemical_list: D017320:HIV Protease Inhibitors; D006834:Hydrazines; D009842:Oligopeptides; C029424:hydrazine; D016333:HIV Protease