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Literature DB >> 7512142

Discovery, synthesis, and bioactivity of bis(heteroaryl)piperazines. 1. A novel class of non-nucleoside HIV-1 reverse transcriptase inhibitors.

D L Romero¹, R A Morge, C Biles, N Berrios-Pena, P D May, J R Palmer, P D Johnson, H W Smith, M Busso, C K Tan.

Abstract

A variety of analogues of 1-[4-methoxy-3,5-dimethylbenzyl]-4-[3-(ethylamino)-2-pyridyl]piperazine hydrochloride (U-80493E) were synthesized and evaluated for their inhibition of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT). Replacement of the substituted aryl moiety with various substituted indoles provided bis(heteroaryl)piperazines (BHAPs) that were 10-100-fold more potent than U-80493E. The pyridyl portion of the lead molecule was found to be very sensitive to modifications. Extensive preclinical evaluations of several of these compounds led to the selection of 1-[(5-methoxyindol-2-yl)carbonyl]-4-[3-(ethylamino)-2- pyridyl]piperazine methanesulfonate (U-87201E, atevirdine mesylate) for clinical evaluation.

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Year: 1994 PMID： 7512142 DOI： 10.1021/jm00033a018

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

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Cited

7 in total

1. The Journey of HIV-1 Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs) from Lab to Clinic.

Authors: Vigneshwaran Namasivayam; Murugesan Vanangamudi; Victor G Kramer; Sonali Kurup; Peng Zhan; Xinyong Liu; Jacob Kongsted; Siddappa N Byrareddy
Journal: J Med Chem Date: 2018-12-27 Impact factor: 7.446

2. Synthesis, biological activity, and crystal structure of potent nonnucleoside inhibitors of HIV-1 reverse transcriptase that retain activity against mutant forms of the enzyme.

Authors: Marshall L Morningstar; Thomas Roth; David W Farnsworth; Marilyn Kroeger Smith; Karen Watson; Robert W Buckheit; Kalyan Das; Wanyi Zhang; Eddy Arnold; John G Julias; Stephen H Hughes; Christopher J Michejda
Journal: J Med Chem Date: 2007-07-31 Impact factor: 7.446

3. Design, synthesis and antifibrotic activities of carbohydrate-modified 1-(substituted aryl)-5-trifluoromethyl-2(1H) pyridones.

Authors: Qinghua Lou; Xiangbao Meng; Zhiqi Lao; Lingling Xuan; Jinye Bai; Qi Hou; Gaoyun Hu; Renna Luo; Lijian Tao; Zhongjun Li
Journal: Molecules Date: 2012-01-17 Impact factor: 4.411

Discovery, synthesis, and bioactivity of bis(heteroaryl)piperazines. 1. A novel class of non-nucleoside HIV-1 reverse transcriptase inhibitors.

1. The Journey of HIV-1 Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs) from Lab to Clinic.

2. Synthesis, biological activity, and crystal structure of potent nonnucleoside inhibitors of HIV-1 reverse transcriptase that retain activity against mutant forms of the enzyme.

3. Design, synthesis and antifibrotic activities of carbohydrate-modified 1-(substituted aryl)-5-trifluoromethyl-2(1H) pyridones.

4. Synthesis and antimicrobial activity of some novel 5-alkyl-6-substituted uracils and related derivatives.

5. Nucleophilic Functionalization of 2-R-3-Nitropyridines as a Versatile Approach to Novel Fluorescent Molecules.

6. Synthesis of Pyrimidine Incorporated Piperazine Derivatives and their Antimicrobial Activity.

7. Synthesis and Facile Dearomatization of Highly Electrophilic Nitroisoxazolo[4,3-b]pyridines.