Hybrid diarylbenzopyrimidine non-nucleoside reverse transcriptase inhibitors as promising new leads for improved anti-HIV-1 chemotherapy

2010 ◽  
Vol 18 (14) ◽  
pp. 5039-5047 ◽  
Author(s):  
Zhao-Sen Zeng ◽  
Qiu-Qin He ◽  
Yong-Hong Liang ◽  
Xiao-Qing Feng ◽  
Fen-Er Chen ◽  
...  
Keyword(s):  
Reverse Transcriptase ◽  
Reverse Transcriptase Inhibitors ◽  
Nucleoside Reverse Transcriptase Inhibitors ◽  
Anti Hiv ◽  
Hiv 1

scholarly journals Synthesis, Anti-HIV Activity, and Metabolic Stability of New Alkenyldiarylmethane HIV-1 Non-Nucleoside Reverse Transcriptase Inhibitors

2005 ◽  
Vol 48 (19) ◽  
pp. 6140-6155 ◽  
Author(s):  
Bo-Liang Deng ◽  
Tracy L. Hartman ◽  
Robert W. Buckheit, ◽  
Christophe Pannecouque ◽  
Erik De Clercq ◽  
...  
Keyword(s):  
Reverse Transcriptase ◽  
Metabolic Stability ◽  
Reverse Transcriptase Inhibitors ◽  
Nucleoside Reverse Transcriptase Inhibitors ◽  
Anti Hiv ◽  
Hiv 1

scholarly journals Nitroimidazoles. V. Synthesis and anti-HIV evaluation of new 5-substituted piperazinyl-4-nitroimidazole derivatives

2007 ◽  
Vol 57 (4) ◽  
pp. 379-393 ◽  
Author(s):  
Yaseen Al-Soud ◽  
Najim Al-Masoudi ◽  
Hamed Hassan ◽  
Erik De Clercq ◽  
Christophe Pannecouque
Keyword(s):  
Reverse Transcriptase ◽  
Imidazole Derivative ◽  
Reverse Transcriptase Inhibitors ◽  
Nucleoside Reverse Transcriptase Inhibitors ◽  
Anti Hiv ◽  
Hiv 1

Nitroimidazoles. V. Synthesis and anti-HIV evaluation of new 5-substituted piperazinyl-4-nitroimidazole derivativesA series of 2-alkylthio-1-[4-(1-benzyl-2-ethyl-4-nitro-1H- -imidazol-5-yl)-piperazin-1-y]lethanones (3-9) and alkyl- [4-(1-benzyl-2-ethyl-4-nitro-1H-imidazol-5-yl)-piperazin- -1-yl)ketones (11-20) as well as the indole analogue22were synthesized from 4-nitro-5-piperazinyl imidazole derivative1, with the aim to develop newly non-nucleoside reverse transcriptase inhibitors (NNRTIs). The newly synthesized compounds were assayed against HIV-1 and HIV-2 in MT-4 cells. Compound2showed inhibition of HIV-1 (EC50 0.45 mg mL-1) and HIV-2 (0.50 mg mL-1), while9showed inhibition of HIV-1 (EC502.48 mg mL-1, SI = 4).

Pointer the Role of Breast Cancer Resistance Protein (BCRP/ABCG2) in Cellular Resistance to HIV-1 Nucleoside Reverse Transcriptase Inhibitors

2005 ◽  
Vol 16 (4) ◽  
pp. 213-216 ◽  
Author(s):  
Xin Wang ◽  
Masanori Baba
Keyword(s):  
Breast Cancer ◽  
Reverse Transcriptase ◽  
Breast Cancer Resistance Protein ◽  
Cancer Resistance ◽  
Reverse Transcriptase Inhibitors ◽  
Nucleoside Reverse Transcriptase Inhibitors ◽  
Cellular Resistance ◽  
Resistance Protein ◽  
Anti Hiv ◽  
Hiv 1

Treatment of HIV-1-infected patients with antiretroviral agents is not always successful due to the emergence of resistant HIV-1 mutants with reduced susceptibility to the agents. However, factors other than viral mutation may also contribute to treatment failure. It has been demonstrated that the ATP-binding cassette (ABC) transporter P-glycoprotein (P-gp/ABCB1) is a key determinant of oral bioavailability of HIV-1 protease inhibitors and their penetration of the central nervous system. More recently, we have found that the expression of breast cancer resistance protein (BCRP/ABCG2) in a CD4+ T-cell line confers cellular resistance to nucleoside reverse transcriptase inhibitors (NRTIs). The anti-HIV-1 activity of the NRTI zidovudine (AZT) was significantly diminished through the reduction of its metabolite levels in MT-4 cells which express high levels of BCRP. Moreover, the BCRP-specific inhibitor fumitremorgin C could completely restore the cytotoxicity of AZT and intracellular levels of its metabolites in BCRP-expressing cells. Thus, BCRP is considered to be a cellular factor that modulates the anti-HIV-1 activity of NRTIs.

Nitroimidazoles Part 6. Synthesis, Structure and in Vitro anti-HIV Activity of New 5-substituted Piperazinyl-4-nitroimidazole Derivatives

2007 ◽  
Vol 18 (4) ◽  
pp. 191-200 ◽  
Author(s):  
Najim A Al-Masoudi ◽  
Yaseen A Al-Soud ◽  
Erik De Clercq ◽  
Christophe Pannecouque
Keyword(s):  
Reverse Transcriptase ◽  
Reverse Transcriptase Inhibitors ◽  
Nucleoside Reverse Transcriptase Inhibitors ◽  
Phthalimide Derivative ◽  
Anti Hiv ◽  
Hiv 1

2-Amino-1-[4-(1-benzyl-2-ethyl-4-nitro-1 H-imidazol-5-yl)piperazin-1-yl]ethanone [6] was prepared from 1-(1-benzyl-2-ethyl-4-nitro-1 H-imidazol-5-yl) piperazine [3]. A series of new 2-oxoethyl-arylamide [9,10] and 2-oxoethyl-arylsulphonamide [11–14] derivatives were synthesized from [6] with the aim of developing new non-nucleoside reverse transcriptase inhibitors. Alternatively, the amine [17] was synthesized from [3] via the phthalimide derivative [16]. The arylsulphonamide derivatives [18–23] and the arylamide analogues [24–26] were synthesized from [17]. The compounds were evaluated for their anti-HIV-1 and anti-HIV-2 activity in MT-4 cells.

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