Literature DB >> 1995896

Synthesis and anti-HIV-1 activity of 4,5,6,7-tetrahydro-5-methylimidazo[4,5,1-jk][1,4]benzodiazepin- 2(1H)-one (TIBO) derivatives.

M J Kukla1, H J Breslin, R Pauwels, C L Fedde, M Miranda, M K Scott, R G Sherrill, A Raeymaekers, J Van Gelder, K Andries.   

Abstract

A series of 6-substituted 4,5,6,7-tetrahydro-5-methylimidazo[4,5,1-jk][1,4]benzodiazepin- 2(1H)-ones (9) have been synthesized and tested for their ability to inhibit the replication of the HIV-1 virus in MT-4 cells. Two synthetic methods are described, one of which allows the synthesis of single enantiomers of the final products. A structure-activity study was done within the series of compounds to determine the optimum group for the 6-position substitution and to determine whether the activity was enantiospecific at the 5-position, which was substituted with a methyl group. The best analogue, 9jj, inhibited HIV-1 with an IC50 of 4 microM, which is comparable to the activity level of DDI, a 2',3'-dideoxynucleoside-type structure undergoing clinical trials as an anti-AIDS therapy.

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Year:  1991        PMID： 1995896     DOI： 10.1021/jm00106a040

Source DB:  PubMed          Journal:  J Med Chem        ISSN： 0022-2623            Impact factor:   7.446


  11 in total

1.  Quantitative structure-activity relationships and comparative molecular field analysis of TIBO derivatised HIV-1 reverse transcriptase inhibitors.

Authors:  S Hannongbua; P Pungpo; J Limtrakul; P Wolschann
Journal:  J Comput Aided Mol Des       Date:  1999-11       Impact factor: 3.686

2.  A molecular-field-based similarity study of non-nucleoside HIV-1 reverse transcriptase inhibitors. 2. The relationship between alignment solutions obtained from conformationally rigid and flexible matching.

Authors:  J Mestres; D C Rohrer; G M Maggiora
Journal:  J Comput Aided Mol Des       Date:  2000-01       Impact factor: 3.686

3.  A molecular-field-based similarity study of non-nucleoside HIV-1 reverse transcriptase inhibitors.

Authors:  J Mestres; D C Rohrer; G M Maggiora
Journal:  J Comput Aided Mol Des       Date:  1999-01       Impact factor: 3.686

4.  Search for non-nucleoside inhibitors of HIV-1 reverse transcriptase using chemical similarity, molecular docking, and MM-GB/SA scoring.

Authors:  Gabriela Barreiro; Cristiano R W Guimarães; Ivan Tubert-Brohman; Theresa M Lyons; Julian Tirado-Rives; William L Jorgensen
Journal:  J Chem Inf Model       Date:  2007-10-20       Impact factor: 4.956

5.  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

6.  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

7.  A mutation in reverse transcriptase of bis(heteroaryl)piperazine-resistant human immunodeficiency virus type 1 that confers increased sensitivity to other nonnucleoside inhibitors.

Authors:  T J Dueweke; T Pushkarskaya; S M Poppe; S M Swaney; J Q Zhao; I S Chen; M Stevenson; W G Tarpley
Journal:  Proc Natl Acad Sci U S A       Date:  1993-05-15       Impact factor: 11.205

8.  2',5'-Bis-O-(tert-butyldimethylsilyl)-3'-spiro-5''-(4''-amino-1'',2''- oxathiole-2'',2'-dioxide)pyrimidine (TSAO) nucleoside analogues: highlyselective inhibitors of human immunodeficiency virus type 1 that are targeted at the viral reverse transcriptase.

Authors:  J Balzarini; M J Pérez-Pérez; A San-Félix; D Schols; C F Perno; A M Vandamme; M J Camarasa; E De Clercq
Journal:  Proc Natl Acad Sci U S A       Date:  1992-05-15       Impact factor: 11.205

9.  Anti-human immunodeficiency virus (HIV) activities of halogenated gomisin J derivatives, new nonnucleoside inhibitors of HIV type 1 reverse transcriptase.

Authors:  T Fujihashi; H Hara; T Sakata; K Mori; H Higuchi; A Tanaka; H Kaji; A Kaji
Journal:  Antimicrob Agents Chemother       Date:  1995-09       Impact factor: 5.191

10.  [2',5'-Bis-O-(tert-butyldimethylsilyl)]-3'-spiro-5''-(4''-amino-1'',2''-oxathiole-2'',2''-dioxide) (TSAO) derivatives of purine and pyrimidinenucleosides as potent and selective inhibitors of human immunodeficiency virus type 1.

Authors:  J Balzarini; M J Pérez-Pérez; A San-Félix; S Velazquez; M J Camarasa; E De Clercq
Journal:  Antimicrob Agents Chemother       Date:  1992-05       Impact factor: 5.191
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