Synthesis and evaluation of a novel class Hsp90 inhibitors containing 1-phenylpiperazine scaffold |
| |
| Affiliation: | 1. Jiang Su Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing 210009, China;2. State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China;3. Department of Medicinal Chemistry, School of Pharmacy, China Pharmaceutical University, Nanjing 210009, China;1. Department of Life Sciences, National University of Kaohsiung, Kaohsiung 811, Taiwan;2. Department of Marine Biotechnology and Resources, National Sun Yat-Sen University, Kaohsiung 804, Taiwan;3. Department of Microbiology, Kaohsiung Medical University, Kaohsiung 807, Taiwan;4. Center of Asia-Pacific Marine Researches, National Sun Yat-Sen University, Kaohsiung, Taiwan;1. Research Institute for Basic Sciences and Department of Chemistry, College of Sciences, Kyung Hee University, Seoul 130-701, Republic of Korea;2. Department of Life and Nanopharmaceutical Science, College of Pharmacy, Kyung Hee University, Seoul 130-701, Republic of Korea |
| |
| Abstract: | ![]()
Previously, we identified 1-(2-(4-bromophenoxy)ethoxy)-3-(4-(2-methoxyphenyl)piperazin-1-yl)propan-2-ol (1) as a novel Hsp90 inhibitor with moderate activity through virtual screening. In this study, we report the optimization process of 1. A series of analogues containing the 1-phenylpiperazine core scaffold were synthesized and evaluated. The structure–activity relationships (SAR) for these compounds was also discussed for further molecular design. This effort afforded the most active inhibitor 13f with improved activity in not only target-based level, but also cell-based level compared with the original hit 1. |
| |
| Keywords: | Hsp90 inhibitors Structure–activity relationships Structure-based drug design |
| 本文献已被 ScienceDirect 等数据库收录！ |
|
