Structure-Based Design of Novel Dihydroalkoxybenzyloxopyrimidine Derivatives as Potent Nonnucleoside Inhibitors of the Human Immunodeficiency Virus Reverse Transcriptase-Reference-Cited by-同舟云学术

Structure-Based Design of Novel Dihydroalkoxybenzyloxopyrimidine Derivatives as Potent Nonnucleoside Inhibitors of the Human Immunodeficiency Virus Reverse Transcriptase

Published:1998-12 Issue:12 Volume:42 Page:3225-3233
ISSN:0066-4804
Container-title:Antimicrobial Agents and Chemotherapy
language:en
Short-container-title:Antimicrob Agents Chemother

Author:

Sudbeck Elise A.¹²³,Mao Chen¹³,Vig Rakesh¹²,Venkatachalam T. K.¹²,Tuel-Ahlgren Lisa⁴,Uckun Fatih M.¹⁴

Affiliation:

1. Drug Discovery Program,1

2. Departments of Chemistry,2

3. Structural Biology,3 and

4. Virology,4 Hughes Institute, St. Paul, Minnesota 55113

Abstract

ABSTRACT Two highly potent dihydroalkoxybenzyloxopyrimidine (DABO) derivatives targeting the nonnucleoside inhibitor (NNI) binding site of human immunodeficiency virus (HIV) reverse transcriptase (RT) have been designed based on the structure of the NNI binding pocket and tested for anti-HIV activity. Our lead DABO derivative, 5-isopropyl-2-[(methylthiomethyl)thio]-6-(benzyl)-pyrimidin-4-(1 H )-one, elicited potent inhibitory activity against purified recombinant HIV RT and abrogated HIV replication in peripheral blood mononuclear cells at nanomolar concentrations (50% inhibitory concentration, <1 nM) but showed no detectable cytotoxicity at concentrations as high as 100 μM.

Publisher

American Society for Microbiology

Subject

Infectious Diseases,Pharmacology (medical),Pharmacology

Link

https://journals.asm.org/doi/pdf/10.1128/AAC.42.12.3225

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