Design,synthesis and biological evaluation of bitopic arylpiperazine-hexahydro-pyrazinoquinolines as preferential dopamine D3 receptor ligands |
| |
| Affiliation: | 1. School of Chemistry and Chemical Engineering, Institute of Pharmaceutical Engineering, Southeast University, 87 Dingjiaqiao, Nanjing, Jiangsu 210096, PR China;2. School of Chemistry and Chemical Engineering, Yancheng Institute of Technology, 211 Jianjun East Road, Yancheng, Jiangsu 224051, PR China;1. Wuya College of Innovation, School of Traditional Chinese Materia Medica, Key Laboratory of Structure-Based Drug Design & Discovery, Ministry of Education, Shenyang Pharmaceutical University, Shenyang 110016, China;2. Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China;3. Department of Pharmacy, Xinjiang Medical University, Urumpi, Xinjiang 830011, China;1. Key Laboratory of Structure-Based Drug Design & Discovery of Ministry of Education, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenhe District, Shenyang 110016, PR China;2. Center for Developmental Therapeutics, Seattle Children’s Research Institute, Division of Gastroenterology and Hepatology, Department of Pediatrics, University of Washington School of Medicine, Seattle, WA 98101, USA;1. Bioprojet-Biotech, 4 rue du Chesnay Beauregard, BP 96205, 35762 Saint-Grégoire, France;2. Heinrich Heine University Düsseldorf, Universitaetsstr. 1, 40225 Duesseldorf, Germany;1. College of Pharmacy and Research Institute of Drug Development, Chonnam National University, Gwangju 61186, Republic of Korea;2. College of Pharmacy and Natural Medicine Research Institute, Mokpo National University, Jeonnam 58554, Republic of Korea;1. Biotechnological and Applied Clinical Sciences Department, University of L׳Aquila, L׳Aquila 67100, Italy;2. Department of Translational Research and New Technology in Medicine, University of Pisa, Pisa 56126, Italy;3. Psychopharmacology Department, Institut de Recherches Servier, Centre de Recherches deCroissy, Croissy-sur-Seine 78290, France |
| |
| Abstract: | Three series of bitobic arylpiperazine-phenyl-hexahydropyrazinoquino- lines analogues were designed, synthesizedand evaluated as a novel class of selective ligands for the dopamine D3 receptor. Compounds 15a (Ki of 11.7 ± 1.8 and 373 nM at D3 and D2, respectively), 15c (Ki of 5.49 and 264 nM at D3 and D2, respectively), 15e (Ki of 14.9 and 325 nM at D3 and D2, respectively), 15i (Ki of 13.8 and 401 nM at D3 and D2, respectively) and 15l (Ki of 13.6 and 870 nM at D3 and D2, respectively) were found to demonstrate good binding affinity and selectivity, and especially compound 15c showeda similar binding affinity and selectivity compared with the contrast drug BP897. |
| |
| Keywords: | Dopamine D3 receptor ligands Bitopic ligands Arylpiperazine-hexahydropyrazinoquinolines analogues Binding affinity Structure-activity relationship |
| 本文献已被 ScienceDirect 等数据库收录！ |
|
