Literature DB >> 17608468

Rationally designed dual inhibitors of HIV reverse transcriptase and integrase.

Zhengqiang Wang, Eric M Bennett, Daniel J Wilson, Christine Salomon, Robert Vince.   

Abstract

Bifunctional inhibitors were designed and synthesized based on 1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)thymine (HEPT)a1 non-nucleoside reverse transcriptase (RT) inhibitors and diketoacid (DKA) integrase (IN) inhibitors. Biochemical studies revealed activity against RT and IN at low nanomolar and low micromolar concentrations, respectively. Exceptionally low IC50 values from a cell-based assay were achieved along with remarkably high therapeutic indices. Compound 7 was identified as the best compound of the series (IC50: 24 nM against RT, 4.4 microM against IN, and 10 nM against HIV-1).

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Year:  2007        PMID： 17608468     DOI： 10.1021/jm070512p

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


  25 in total

1.  N-3 Hydroxylation of Pyrimidine-2,4-diones Yields Dual Inhibitors of HIV Reverse Transcriptase and Integrase.

Authors:  Jing Tang; Kasthuraiah Maddali; Christine D Dreis; Yuk Y Sham; Robert Vince; Yves Pommier; Zhengqiang Wang
Journal:  ACS Med Chem Lett       Date:  2011-01       Impact factor: 4.345

2.  6-Cyclohexylmethyl-3-hydroxypyrimidine-2,4-dione as an inhibitor scaffold of HIV reverase transcriptase: Impacts of the 3-OH on inhibiting RNase H and polymerase.

Authors:  Jing Tang; Karen A Kirby; Andrew D Huber; Mary C Casey; Juan Ji; Daniel J Wilson; Stefan G Sarafianos; Zhengqiang Wang
Journal:  Eur J Med Chem       Date:  2017-01-30       Impact factor: 6.514

3.  Discovery of dimeric inhibitors by extension into the entrance channel of HIV-1 reverse transcriptase.

Authors:  Anil R Ekkati; Mariela Bollini; Robert A Domaoal; Krasimir A Spasov; Karen S Anderson; William L Jorgensen
Journal:  Bioorg Med Chem Lett       Date:  2012-01-05       Impact factor: 2.823

4.  Pharmacophore-based design of novel 3-hydroxypyrimidine-2,4-dione subtypes as inhibitors of HIV reverse transcriptase-associated RNase H: Tolerance of a nonflexible linker.

Authors:  Jing Tang; Ha T Do; Andrew D Huber; Mary C Casey; Karen A Kirby; Daniel J Wilson; Jayakanth Kankanala; Michael A Parniak; Stefan G Sarafianos; Zhengqiang Wang
Journal:  Eur J Med Chem       Date:  2019-02-02       Impact factor: 6.514

5.  3-Hydroxypyrimidine-2,4-diones as Selective Active Site Inhibitors of HIV Reverse Transcriptase-Associated RNase H: Design, Synthesis, and Biochemical Evaluations.

Authors:  Jing Tang; Feng Liu; Eva Nagy; Lena Miller; Karen A Kirby; Daniel J Wilson; Bulan Wu; Stefan G Sarafianos; Michael A Parniak; Zhengqiang Wang
Journal:  J Med Chem       Date:  2016-03-08       Impact factor: 7.446

6.  Design, synthesis and biological evaluations of N-Hydroxy thienopyrimidine-2,4-diones as inhibitors of HIV reverse transcriptase-associated RNase H.

Authors:  Jayakanth Kankanala; Karen A Kirby; Andrew D Huber; Mary C Casey; Daniel J Wilson; Stefan G Sarafianos; Zhengqiang Wang
Journal:  Eur J Med Chem       Date:  2017-09-28       Impact factor: 6.514

7.  6-Arylthio-3-hydroxypyrimidine-2,4-diones potently inhibited HIV reverse transcriptase-associated RNase H with antiviral activity.

Authors:  Lei Wang; Jing Tang; Andrew D Huber; Mary C Casey; Karen A Kirby; Daniel J Wilson; Jayakanth Kankanala; Jiashu Xie; Michael A Parniak; Stefan G Sarafianos; Zhengqiang Wang
Journal:  Eur J Med Chem       Date:  2018-07-17       Impact factor: 6.514

8.  6-Biphenylmethyl-3-hydroxypyrimidine-2,4-diones potently and selectively inhibited HIV reverse transcriptase-associated RNase H.

Authors:  Lei Wang; Jing Tang; Andrew D Huber; Mary C Casey; Karen A Kirby; Daniel J Wilson; Jayakanth Kankanala; Michael A Parniak; Stefan G Sarafianos; Zhengqiang Wang
Journal:  Eur J Med Chem       Date:  2018-07-17       Impact factor: 6.514

9.  Enantioselective total synthesis of plectosphaeroic acid B.

Authors:  Salman Y Jabri; Larry E Overman
Journal:  J Am Chem Soc       Date:  2013-03-06       Impact factor: 15.419

10.  Design, Synthesis, and Biological Evaluations of Hydroxypyridonecarboxylic Acids as Inhibitors of HIV Reverse Transcriptase Associated RNase H.

Authors:  Jayakanth Kankanala; Karen A Kirby; Feng Liu; Lena Miller; Eva Nagy; Daniel J Wilson; Michael A Parniak; Stefan G Sarafianos; Zhengqiang Wang
Journal:  J Med Chem       Date:  2016-04-29       Impact factor: 7.446
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