Synthesis and biological evaluation of substituted 4-(thiophen-2-ylmethyl)-2H-phthalazin-1-ones as potent PARP-1 inhibitors |
| |
| Institution: | 1. Laboratory of Computer-Aided Drug Design & Discovery, Beijing Institute of Pharmacology and Toxicology, Beijing 100850, PR China;2. Department of Traditional Chinese Materia Medica and Neuroimmunopharmacology, Beijing Institute of Pharmacology and Toxicology, Beijing 100850, PR China;1. Beijing Institute of Pharmacology & Toxicology, 27 Tai-Ping Road, Beijing 100850, China;2. Key Laboratory of Medical Molecular Virology of Ministries of Education and Health, Shanghai Medical College and Institute of Medical Microbiology, Fudan University, Shanghai 200032, China;3. Lindsley F. Kimball Research Institute, New York Blood Center, NY 10065, USA;4. Natural Products Research Laboratories, UNC Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC 27599-7568, USA;5. Chinese Medicine Research and Development Center, China Medical University and Hospital, Taichung, Taiwan;1. CAMS Key Laboratory of Antiviral Drug Research, Beijing Key Laboratory of Antimicrobial Agents, NHC Key Laboratory of Biotechnology of Antibiotics, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, China;2. Department of Pharmaceutical Chemistry, School of Pharmacy, Hebei Medical University, Shijiazhuang, 050017, China;3. Chemical Medicine Department, R&D Center, Tasly Pharmaceutical Group Co. Ltd., Tianjin, 300410, China;1. Department of Medicinal Chemistry, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zuchongzhi Road, Shanghai 201203, PR China;2. Division of Antitumor Pharmacology, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zuchongzhi Road, Shanghai 201203, PR China |
| |
| Abstract: | We have developed a series of substituted 4-(thiophen-2-ylmethyl)-2H-phthalazin-1-ones as potent PARP-1 inhibitors. Preliminary biological evaluation indicated that most compounds possessed inhibitory potencies comparable to, or higher than AZD-2281. Among these compounds, 18q appeared to be the most notable one, which displayed an 8-fold improvement in enzymatic activity compared to AZD-2281. These efforts lay the foundation for our further investigation. |
| |
| Keywords: | PARP-1 inhibitor Synthesis Biological evaluation Antitumor |
| 本文献已被 ScienceDirect 等数据库收录！ |
|
