Evaluation of retro-inverso modifications of HTLV-1 protease inhibitors containing a hydroxyethylamine isoster

Tadashi Tatsumi; Chiyuki Awahara; Hiromi Naka; Saburo Aimoto; Hiroyuki Konno; Kazuto Nosaka; Kenichi Akaji

doi:10.1016/j.bmc.2010.02.019

Evaluation of retro-inverso modifications of HTLV-1 protease inhibitors containing a hydroxyethylamine isoster

Bioorg Med Chem. 2010 Apr 1;18(7):2720-7. doi: 10.1016/j.bmc.2010.02.019. Epub 2010 Feb 18.

Authors

Tadashi Tatsumi¹, Chiyuki Awahara, Hiromi Naka, Saburo Aimoto, Hiroyuki Konno, Kazuto Nosaka, Kenichi Akaji

Affiliation

¹ Department of Medicinal Chemistry, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kita-ku, Kyoto 603-8334, Japan.

PMID: 20226680
DOI: 10.1016/j.bmc.2010.02.019

Abstract

Effects of retro-inverso (RI) modifications of HTLV-1 protease inhibitors containing a hydroxyethylamine isoster backbone were clarified. Construction of the isoster backbone was achieved by a stereoselective aldol reaction. Four diastereomers with different configurations at the isoster hydroxyl site and the scissile site substituent were synthesized. Inhibitory activities of the new inhibitors suggest that partially modified RI inhibitors would interact with HTLV-1 protease in the same manner as the parent hydroxyethylamine inhibitor.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Aspartic Acid Endopeptidases / antagonists & inhibitors*
Aspartic Acid Endopeptidases / genetics
Deanol / analogs & derivatives*
Deanol / chemical synthesis*
Deanol / pharmacology*
Dose-Response Relationship, Drug
Human T-lymphotropic virus 1 / drug effects
Human T-lymphotropic virus 1 / genetics
Indicators and Reagents
Mutation
Protease Inhibitors / chemical synthesis*
Protease Inhibitors / pharmacology*
Structure-Activity Relationship

Substances

Indicators and Reagents
Protease Inhibitors
Deanol
Aspartic Acid Endopeptidases
HTLV-1 protease