Design and synthesis of pseudo-symmetric HIV protease inhibitors containing a novel hydroxymethylcarbonyl (HMC)-hydrazide isostere

Koushi Hidaka; Tooru Kimura; Yoshio Hayashi; Keith F McDaniel; Tatyana Dekhtyar; Lynn Colletti; Yoshiaki Kiso

doi:10.1016/s0960-894x(02)00848-x

Design and synthesis of pseudo-symmetric HIV protease inhibitors containing a novel hydroxymethylcarbonyl (HMC)-hydrazide isostere

Bioorg Med Chem Lett. 2003 Jan 6;13(1):93-6. doi: 10.1016/s0960-894x(02)00848-x.

Authors

Koushi Hidaka¹, Tooru Kimura, Yoshio Hayashi, Keith F McDaniel, Tatyana Dekhtyar, Lynn Colletti, Yoshiaki Kiso

Affiliation

¹ Department of Medicinal Chemistry, Center of Frontier Reseach in Medicinal Science, Kyoto Pharmaceutical University, Yamashina-ku, Japan.

PMID: 12467624
DOI: 10.1016/s0960-894x(02)00848-x

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.

MeSH terms

Drug Design
HIV Protease / drug effects
HIV Protease Inhibitors / chemical synthesis*
HIV Protease Inhibitors / pharmacology
Humans
Hydrazines / chemistry*
Inhibitory Concentration 50
Molecular Mimicry
Oligopeptides / chemical synthesis*
Oligopeptides / pharmacology
Structure-Activity Relationship

Substances

HIV Protease Inhibitors
Hydrazines
Oligopeptides
hydrazine
HIV Protease