Structural modifications of CH(OH)-DAPYs as new HIV-1 non-nucleoside reverse transcriptase inhibitors |
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| Affiliation: | 1. Department of Chemistry, Fudan University, Shanghai 200433, People’s Republic of China;2. Institute of Biomedical Science, Fudan University, Shanghai 200433, People’s Republic of China;3. Rega Institute for Medical Research, Katholieke Universiteit Leuven, 10 Minderbroedersstraat, B-3000 Leuven, Belgium;1. Department of Chemical and Environmental Sciences, Materials and Surface Science Institute, University of Limerick, Limerick, Ireland;2. Department of Applied Chemistry, Building Los Acebos, Public University of Navarra, Campus of Arrosadia, E-31006 Pamplona, Spain;1. School of Science, Tianjin Chengjian University, Tianjin 300384, China;2. College of Mathematics and Information Science, Hebei Normal University, Shijiazhuang 050024, China;3. College of Mathematics and Information Science, Hebei Normal University, Shijiazhuang 050024, China;1. Institute of Ion Physics and Applied Physics, University of Innsbruck, A-6020 Innsbruck, Austria;2. Kazan National Research Technological University, 420015 Kazan, Republic of Tatarstan, Russian Federation;3. Department of Chemistry, York University, Toronto, ON M3J 1P3, Canada;1. Divisione Clinicizzata di Malattie Infettive, Dipartimento di Scienze Biomediche e Cliniche ‘Luigi Sacco'', Universita’ degli Studi di Milano, Milano;2. ITB-CNR, Segrate;3. Malattie Infettive & Microbiologia, Universita’ degli Studi di Genova, Genova;4. Istituto di Microbiologia & Virologia, Universita’ degli Studi di Siena, Siena;5. Istituto di Microbiologia and Virologia, Ospedali Riuniti di Bergamo, Bergamo;6. Istituto di Virologia, Università degli Studi di Bari, Bari;7. Istituto di Virologia, Istituto Scientifico San Raffaele, Milano;8. Virologia, Policlinico Universitario, Modena;9. Clinica Malattie Infettive, Università degli Studi di Bari, Bari;10. Clinica Malattie Infettive, Istituto Scientifico San Raffaele, Milano;11. Immunologia Clinica e Tipizzazione Tessutale, Università Politecnica delle Marche, Torrette di Ancona;12. Malattie Infettive, Ospedale Pediatrico Meyer, Firenze;13. Istituto di Virologia, Ospedale Santo Spirito, Pescara, Italy |
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| Abstract: | A series of CR2(OH)-diarylpyrimidine derivatives (CR2(OH)-DAPYs) featuring a hydrophobic group at CH(OH) linker between wing I and the central pyrimidine were synthesized and evaluated for their anti-HIV activity in MT-4 cell cultures. All the target compounds except for compound 3k displayed inhibitory activity against HIV-1 wild-type with EC50 values ranging from 7.21 ± 1.99 to 0.067 ± 0.006 μM. Among them, compound 3d showed the most potent anti-HIV-1 activity (EC50 = 0.067 ± 0.006 μM, SI > 592), which was approximately 2-fold more potent than the reference drugs nevirapine (NVP) and delaviridine (DLV) in the same assay. In addition, the binding modes with HIV-1 RT and the preliminary SAR studies of these new derivatives were also investigated. |
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| Keywords: | HIV-1 NNRTIs Diarylpyrimidine SAR Antiviral activity |
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