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Dihydropyrimidinone-isatin hybrids as novel non-nucleoside HIV-1 reverse transcriptase inhibitors
Affiliation:1. Jaipur National University, Jagatpura, Jaipur, India;2. National Chemical Laboratory (NCL), Pune, India;3. Sinhgad Institute of Pharmacy, Narhe, Pune, India;4. Faculty of Pharmacy, The Maharaja Sayajirao University of Baroda, Vadodara, India;1. Department of Chemistry, Karnatak University, Dharwad 580 003, Karnataka, India;2. Novel Drug Design and Discovery Laboratory, Department of Pharmaceutical Chemistry, S.E.T’s College of Pharmacy, Sangolli Rayanna Nagar, Dharwad 580002, Karnataka, India;3. Department of Chemistry, G.S.S. College, Belagavi, Karnataka, India;1. Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, 44, West Culture Road, 250012, Jinan, Shandong, PR China;2. Rega Institute for Medical Research, KU Leuven, Minderbroedersstraat 10, B-3000 Leuven, Belgium;1. Department of Chemistry, Capital Normal University, Beijing, 100048, China;2. State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, China;1. Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, 44, West Culture Road, 250012 Ji’nan, Shandong, PR China;2. Institute of Pharmacology, School of Medicine, Shandong University, 44, West Culture Road, 250012 Ji’nan, Shandong, PR China;3. Rega Institute for Medical Research, KU Leuven, Minderbroedersstraat 10, B-3000 Leuven, Belgium;1. Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, 44, West Culture Road, 250012 Jinan, Shandong, PR China;2. Rega Institute for Medical Research, KU Leuven, Minderbroedersstraat 10, B-3000 Leuven, Belgium;1. Center for Drug Design, Academic Health Center, University of Minnesota, Minneapolis, MN 55455, USA;2. Department of Molecular Microbiology and Immunology and Department of Biochemistry, University of Missouri School of Medicine, Christopher S. Bond Life Sciences Center, Columbia, MO 65211, USA
Abstract:A novel series of substituted N-(2-(2,3-dioxoindolin-1-yl)acetyl)-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxamide was designed, synthesized and evaluated for in vitro Reverse Transcriptase (RT) inhibitory activity. This series is a combination of peculiar structural features from leading scaffolds of [(2-hydroxyethoxy)methyl]-6-(phenylthio)thymine (HEPT) and oxyindole. In vitro screening led to identification of two hybrids (9c and 9d) possessing higher RT inhibitory activity than the standard rilpivirine. Docking study was performed to study the binding orientations of synthesized hybrids towards RT enzyme.
Keywords:NNRTI  Hybrid approach  Microwave assisted synthesis  Molecular docking  G-score  DEZVTPXFPJSDNG-UHFFFAOYSA-N  VIJXFOPOUFIAIV-UHFFFAOYSA-N  PEBAGSPBNBEURG-UHFFFAOYSA-N  PSXNTRZWHQRGKA-UHFFFAOYSA-N  DQDCNUZZSNHEIQ-UHFFFAOYSA-N  QWQAULDYHCAJNC-UHFFFAOYSA-N  NRHFPTSPYAYBDF-UHFFFAOYSA-N  ITYVASSGCXOMKD-UHFFFAOYSA-N  MSNICPMSBMLZEX-UHFFFAOYSA-N  ZTEWFTXFPBHDHC-UHFFFAOYSA-N  LYVDAOOZEQNJKA-UHFFFAOYSA-N  RPOPHFPAEBROPY-UHFFFAOYSA-N  BVNHZDLWEIVZJX-UHFFFAOYSA-N  AZKPZKNCBYFKJA-UHFFFAOYSA-N  ZDOXYBQBCAXRDD-MTDXEUNCSA-N  RIWCEDQDLPQKCJ-YZSQISJMSA-N  YBTAMRWSQLCOPZ-OVVQPSECSA-N  GOEQFMDRSLUSHK-NJZRLIGZSA-N  SGTBQLZNYJFNTM-MWAVMZGNSA-N  QZNJWZNDWJNOSN-NJZRLIGZSA-N  LJQAIMJHXPBCNX-XIEYBQDHSA-N  NPMGOAGVCCHHKA-UHFFFAOYSA-N
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