Synthesis of bi-/tricyclic azasugars fused thiazinan-4-one and their HIV-RT inhibitory activity |
| |
| Affiliation: | 1. School of Pharmacy and Biomedical Sciences, University of Central Lancashire, Maudland Building, Preston, Lancashire PR1 2HE, UK;2. Brain Tumour Research Centre, University of Wolverhampton, Wulfruna Street, Wolverhampton WV1 1LY, UK;1. CQC, Department of Chemistry, University of Coimbra, Rua Larga, 3004-535 Coimbra, Portugal;2. Departamento de Química & QOPNA, University of Aveiro, 3810-193 Aveiro, Portugal;1. Laboratoire des Biomolécules, Département de chimie, École normale supérieure, PSL Research University, Sorbonne Universités, UPMC Univ. Paris 06, CNRS, 24 rue Lhomond, 75005 Paris, France;2. Univ. Grenoble Alpes, CNRS, CEA, Institut de Biologie Structurale, Avenue des Martyrs, F-38044 Grenoble, France;1. School of Pharmacy, Xuzhou Medical College, Xuzhou 221004, People’s Republic of China;2. State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, People’s Republic of China;3. Department of Environmental Pharmacy, Tianjin Institute of Health and Environmental Medicine, Tianjin 300050, People’s Republic of China;1. Department of Biochemistry and Biotechnology, Laboratory of Bio-Organic Chemistry, University of Thessaly, 26 Ploutonos Str., 41221 Larissa, Greece;2. Department of Chemistry, Aristotle University of Thessaloniki, University Campus, 54124 Thessaloniki, Greece;3. Rega Institute for Medical Research, KU Leuven, B-3000 Leuven, Belgium |
| |
| Abstract: | Novel bi-/tricyclic azasugars fused thiazinan-4-one were conveniently synthesized by the tandem Staudinger/aza-Wittig/cyclization reaction under microwave radiation. The aryl group (phenyl or pyridyl) in mercaptan acid had an important effect on the formation of the diastereomers of the tricyclic hybrids 12b–15b. The new bi/tricyclic azasugars 3a–8a, 4b, 6b, 8b and the known ones 2a, 2b were examined for their HIV reverse transcriptase (RT) inhibitory activities. The result showed that compounds 2a–b, 4a, 4b, 5a, and 6a could effectively inhibit RT activity. Among them, the tricyclic azasugar 5a was the best one with the IC50 value of 0.49 μM. Structure–activity relationship analysis suggested that the phenyl group in the tricyclic azasugars was benefit for their anti-HIV RT activity. |
| |
| Keywords: | Bi-/tricyclic azasugar Thiazinan-4-one Staudinger/aza-Wittig Anti-HIV RT activity Microwave radiation |
| 本文献已被 ScienceDirect 等数据库收录！ |
|
