Synthesis of potent C(2)-symmetric, diol-based hiv-1 protease inhibitors. Investigation of thioalkyl and thioaryl P1/P1' substituents

A Mühlman; B Classon; A Hallberg; B Samuelsson

doi:10.1021/jm0011169

Synthesis of potent C(2)-symmetric, diol-based hiv-1 protease inhibitors. Investigation of thioalkyl and thioaryl P1/P1' substituents

J Med Chem. 2001 Oct 11;44(21):3402-6. doi: 10.1021/jm0011169.

Authors

A Mühlman¹, B Classon, A Hallberg, B Samuelsson

Affiliation

¹ Department of Organic Chemistry, Arrhenius Laboratory, Stockholm University, SE-106 91 Stockholm, Sweden.

PMID: 11585445
DOI: 10.1021/jm0011169

Abstract

The synthesis of novel, potent diol-based HIV-1 protease inhibitors, having either -SAr, -SCH(2)Ar, or -SCH(2)R groups as P1/P1' substituents is described. They can be prepared using a straightforward synthesis involving a thiol nucleophilic ring opening of a diepoxide. Inhibitor 13 was found to be a potent inhibitor of HIV-1 PR, showing good antiviral activity in a cell-based assay.

Publication types

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

MeSH terms

Cell Line
Cloning, Molecular
Cytopathogenic Effect, Viral / drug effects
HIV Protease / metabolism
HIV Protease Inhibitors / chemical synthesis*
HIV Protease Inhibitors / chemistry
HIV Protease Inhibitors / pharmacology
HIV-1*
Humans
Magnetic Resonance Spectroscopy
Structure-Activity Relationship
Thiophenes / chemical synthesis*
Thiophenes / chemistry
Thiophenes / pharmacology

Substances

HIV Protease Inhibitors
N1,N6-di-(hydroxy-1-indanyl)-3,4-dihydroxy-2,5-di-(thiophen-3-ylsulfanyl)hexanediamide
Thiophenes
HIV Protease