Synthesis and antidepressant-like activity of novel alkoxy-piperidine derivatives targeting SSRI/5-HT1A/5-HT7 |
| |
| Affiliation: | 1. Shanghai Institute of Pharmaceutical Industry, China State Institute of Pharmaceutical Industry, 285 Gebaini Road, Shanghai 201203, PR China;2. School of Engineering, China Pharmaceutical University, 639 Longmian Avenue, Nanjing 211198, PR China;1. Department of Clinical Pharmacy, Jagiellonian University Medical College, 9 Medyczna Street, 30-688 Kraków, Poland;2. Department of Medicinal Chemistry, Jagiellonian University Medical College, 9 Medyczna Street, 30-688 Kraków, Poland;3. Institute of Pharmacology, Polish Academy of Sciences, 12 Smętna Street, 31-343 Kraków, Poland;1. Faculty of Chemical Engineering and Technology, Institute of Organic Chemistry and Technology, Cracow University of Technology, 24 Warszawska Street, Cracow 31-155, Poland;2. Department of Medicinal Chemistry, Institute of Pharmacology – Polish Academy of Sciences, 12 Smętna Street, Cracow 31-343, Poland;1. CAS Key Laboratory for Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zuchongzhi Road, Shanghai 201203, China;2. University of Chinese Academy of Sciences, No. 19A Yuquan Road, Beijing 100049, China;3. Topharman Shanghai Co., Ltd, 388 Jialilue Road, Shanghai 201203, China;1. Convergence Research Center for Diagnosis, Treatment and Care System of Dementia, Korea Institute of Science and Technology, 5, Hwarang-ro 14-gil, Seongbuk-gu, Seoul 02792, Republic of Korea;2. Department of Chemistry, Korea University, 145 Anam-ro, Seongbuk-gu, Seoul 02841, Republic of Korea;3. Bio Platform Technology Research Center, Korea Research Institute of Chemical Technology, Gajeong-ro 141, Yuseong-gu, Daejon 34114, Republic of Korea;4. Division of Bio-Medical Science & Technology, KIST School, Korea University of Science and Technology, 5, Hwarang-ro 14-gil, Seongbuk-gu, Seoul 02792, Republic of Korea;1. Dipartimento di Scienze del Farmaco, Università di Catania, viale A. Doria 6, Catania 95125, Italy;2. IRCCS-Istituto di Ricerche Farmacologiche ‘Mario Negri’, via La Masa 19, Milano 20156, Italy;1. Jagiellonian University Medical College, Faculty of Pharmacy, Department of Bioorganic Chemistry, Chair of Organic Chemistry, Poland;2. Jagiellonian University Medical College, Faculty of Pharmacy, Department of Pharmacodynamics, Poland;3. Jagiellonian University Medical College, Faculty of Pharmacy, Chair and Department of Toxicology, Poland;4. Jagiellonian University Medical College, Faculty of Pharmacy, Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Poland;5. Jagiellonian University Medical College, Faculty of Pharmacy, Department of Pharmaceutical Biochemistry, Poland |
| |
| Abstract: | A series of novel alkoxy-piperidine derivatives were synthesized and evaluated for their serotonin reuptake inhibitory and binding affinities for 5-HT1A/5-HT7 receptors. In vivo antidepressant activities of the selective compounds were explored using the forced swimming test (FST) and tail suspension test (TST) in mice. The results showed that compounds 7a (reuptake inhibition (RUI), IC50 = 177 nM; 5-HT1A, Ki = 12 nM; 5-HT7, Ki = 25 nM) and 15g (RUI, IC50 = 85 nM; 5-HT1A, Ki = 17 nM; 5-HT7, Ki = 35 nM) were potential antidepressant agents in animal behavioral models with high 5-HT1A/5-HT7 receptor affinities and moderate serotonin reuptake inhibition, and good metabolic stability in vitro. |
| |
| Keywords: | Antidepressant Alkoxy-piperidine derivatives Serotonin reuptake inhibition |
| 本文献已被 ScienceDirect 等数据库收录！ |
|
