Structure-activity relationships of novel HIV-1 protease inhibitors containing the 3-amino-2-chlorobenzoyl-allophenylnorstatine structure

Tsutomu Mimoto; Satoshi Nojima; Keisuke Terashima; Haruo Takaku; Makoto Shintani; Hideya Hayashi

doi:10.1016/j.bmc.2007.10.062

Structure-activity relationships of novel HIV-1 protease inhibitors containing the 3-amino-2-chlorobenzoyl-allophenylnorstatine structure

Bioorg Med Chem. 2008 Feb 1;16(3):1299-308. doi: 10.1016/j.bmc.2007.10.062. Epub 2007 Oct 23.

Authors

Tsutomu Mimoto¹, Satoshi Nojima, Keisuke Terashima, Haruo Takaku, Makoto Shintani, Hideya Hayashi

Affiliation

¹ Drug Research Division, Dainippon Sumitomo Pharma Co., Ltd., Enoki 33-94, Suita, Osaka 564-0053, Japan. tsutomu-mimoto@ds-pharma.co.jp

PMID: 17981045
DOI: 10.1016/j.bmc.2007.10.062

Abstract

A series of peptidomimetic human immunodeficiency virus (HIV) protease inhibitors containing substituted allophenylnorstatine (Apns: (2S,3S)-3-amino-2-hydroxy-4-phenylbutyric acid) were designed and synthesized. From the structure-activity relationship of this series of compounds, SM-309515 was found to have potent antiviral activity against wild-type and resistant HIV-1s and to possess a desirable pharmacokinetic profile in dogs.

MeSH terms

Animals
Dogs
Drug Design
HIV Protease Inhibitors / chemical synthesis
HIV Protease Inhibitors / chemistry*
HIV Protease Inhibitors / metabolism
HIV Protease Inhibitors / pharmacology*
HIV-1 / drug effects
HIV-1 / enzymology
HIV-1 / genetics
Hepatocytes / drug effects
Hepatocytes / enzymology
Humans
Molecular Structure
Mutation / genetics
Phenylbutyrates / chemical synthesis
Phenylbutyrates / chemistry*
Phenylbutyrates / pharmacology*
Sensitivity and Specificity
Structure-Activity Relationship

Substances

HIV Protease Inhibitors
Phenylbutyrates
3-amino-2-hydroxy-4-phenylbutanoic acid