Literature DB >> 1725247

A TIBO derivative, R82913, is a potent inhibitor of HIV-1 reverse transcriptase with heteropolymer templates.

E L White1, R W Buckheit, L J Ross, J M Germany, K Andries, R Pauwels, P A Janssen, W M Shannon, M A Chirigos.   

Abstract

R82913, (+)-S-4,5,6,7-tetrahydro-9-chloro-5-methyl-6-(3-methyl-2-butenyl)- imidazo[4,5,1-jk][1,4]-benzodiazepin-2(1H)-thione (a TIBO derivative), inhibited the replication of thirteen different strains of HIV-1 in CEM cells with a median IC50 of 0.15 microM. The concentration of compound that killed 50% of the cells was much higher (46 microM), indicating that R82913 has a high selectivity index. R82913 was 20-fold more potent than AZT-TP in the inhibition of HIV-1 reverse transcriptase in an assay using a naturally occurring template (ribosomal RNA) that more accurately resembles native viral RNA than a synthetic homopolymer. With this template, R82913 inhibited HIV-1 reverse transcriptase with an ID50 (0.01 microM) that is equal to, or lower than, the IC50 for this compound in all of our cell culture assays (0.01-0.65 microM). R82913 has no effect on the replication of HIV-2 in CEM cells and does not inhibit the reverse transcriptase from this virus.

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Year:  1991        PMID： 1725247     DOI： 10.1016/0166-3542(91)90005-c

Source DB:  PubMed          Journal:  Antiviral Res        ISSN： 0166-3542            Impact factor:   5.970


  17 in total

1.  Treatment of human immunodeficiency virus type 1 (HIV-1)-infected cells with combinations of HIV-1-specific inhibitors results in a different resistance pattern than does treatment with single-drug therapy.

Authors:  J Balzarini; A Karlsson; M J Pérez-Pérez; M J Camarasa; W G Tarpley; E De Clercq
Journal:  J Virol       Date:  1993-09       Impact factor: 5.103

Review 2.  Antiviral therapy for human immunodeficiency virus infections.

Authors:  E De Clercq
Journal:  Clin Microbiol Rev       Date:  1995-04       Impact factor: 26.132

3.  Human immunodeficiency virus type 1 (HIV-1) strains selected for resistance against the HIV-1-specific [2',5'-bis-O-(tert-butyldimethylsilyl)-3'-spiro- 5''-(4''-amino-1'',2''-oxathiole-2'',2''-dioxide)]-beta-D-pentofurano syl (TSAO) nucleoside analogues retain sensitivity to HIV-1-specific nonnucleoside inhibitors.

Authors:  J Balzarini; A Karlsson; A M Vandamme; M J Pérez-Pérez; H Zhang; L Vrang; B Oberg; K Bäckbro; T Unge; A San-Félix
Journal:  Proc Natl Acad Sci U S A       Date:  1993-08-01       Impact factor: 11.205

Review 4.  Antiviral therapy in human immunodeficiency virus infections. Current status (Part II).

Authors:  E Sandström; B Oberg
Journal:  Drugs       Date:  1993-05       Impact factor: 9.546

5.  Diarylsulfones, a new chemical class of nonnucleoside antiviral inhibitors of human immunodeficiency virus type 1 reverse transcriptase.

Authors:  J B McMahon; R J Gulakowski; O S Weislow; R J Schultz; V L Narayanan; D J Clanton; R Pedemonte; F W Wassmundt; R W Buckheit; W D Decker
Journal:  Antimicrob Agents Chemother       Date:  1993-04       Impact factor: 5.191

6.  Differential activities of 1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)thymine derivatives against different human immunodeficiency virus type 1 mutant strains.

Authors:  J Balzarini; M Baba; E De Clercq
Journal:  Antimicrob Agents Chemother       Date:  1995-04       Impact factor: 5.191

7.  3'-Azido-3'-deoxythymidine-induced reduction in the ability of uninfected CD4-expressing cells to participate in syncytium formation.

Authors:  R W Buckheit; J Germany-Decker; K Qualls-Goodwin; B J Bowdon; W M Shannon
Journal:  Proc Natl Acad Sci U S A       Date:  1992-09-01       Impact factor: 11.205

8.  L-696,229 specifically inhibits human immunodeficiency virus type 1 reverse transcriptase and possesses antiviral activity in vitro.

Authors:  M E Goldman; J A O'Brien; T L Ruffing; J H Nunberg; W A Schleif; J C Quintero; P K Siegl; J M Hoffman; A M Smith; E A Emini
Journal:  Antimicrob Agents Chemother       Date:  1992-05       Impact factor: 5.191

9.  Identification of the human immunodeficiency virus reverse transcriptase residues that contribute to the activity of diverse nonnucleoside inhibitors.

Authors:  J H Condra; E A Emini; L Gotlib; D J Graham; A J Schlabach; J A Wolfgang; R J Colonno; V V Sardana
Journal:  Antimicrob Agents Chemother       Date:  1992-07       Impact factor: 5.191

10.  Comprehensive mutant enzyme and viral variant assessment of human immunodeficiency virus type 1 reverse transcriptase resistance to nonnucleoside inhibitors.

Authors:  V W Byrnes; V V Sardana; W A Schleif; J H Condra; J A Waterbury; J A Wolfgang; W J Long; C L Schneider; A J Schlabach; B S Wolanski
Journal:  Antimicrob Agents Chemother       Date:  1993-08       Impact factor: 5.191
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