Synthesis and dopaminergic activity of a series of new 1-aryl tetrahydroisoquinolines and 2-substituted 1-aryl-3-tetrahydrobenzazepines |
| |
| Affiliation: | 1. Departamento de Química Orgánica, Facultad de Ciencias, Universidad de Málaga, Campus de Teatinos s/n, 29071 Málaga, Spain;2. Departamento de Biología Celular, Genética y Fisiología, Facultad de Ciencias, Universidad de Málaga, Campus de Teatinos s/n, 29071 Málaga, Spain;1. School of Traditional Chinese Materia Medica, Key Laboratory of Structure-Based Drug Design and Discovery, Ministry of Education, Shenyang Pharmaceutical University, Shenyang 110016, People’s Republic of China;2. Xiamen Institute for Food and Drug Quality Control, Xiamen 3161012, People’s Republic of China;3. Chinese People''s Liberation Army 210 Hospital, Dalian 116021, People’s Republic of China;1. N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, 119991 Moscow, Russian Federation;2. I. M. Sechenov First Moscow State Medical University, 119991Moscow, Russian Federation;1. Institute of Bioorganic Chemistry and Petrochemistry, National Academy of Sciences of Ukraine, 02660 Kyiv-94, Ukraine;2. Institute of Problems of Chemical Physics, Russian Academy of Sciences, 142432 Chernogolovka, Moscow Region, Russian Federation;3. A. N. Nesmeyanov Institute of Organoelement Compounds, Russian Academy of Sciences, 119991 Moscow, Russian Federation;1. Department of Neurochemistry, Maj Institute of Pharmacology, Polish Academy of Sciences, Kraków, Poland;2. Department of Pathophysiology, Forensic and Administration of Veterinary Medicine, Faculty of Veterinary Medicine, University of Warmia and Mazury in Olsztyn, Olsztyn, Poland;3. Department of Pharmacokinetics and Drug Metabolism, Maj Institute of Pharmacology, Polish Academy of Sciences, Kraków, Poland;1. Faculty of Agriculture, Ehime University, 3-5-7 Tarumi, Matsuyama, Ehime 790-8566, Japan;2. South Ehime Fisheries Research Center, 1289-1 Funakoshi, Ainan, Ehime 798-4292, Japan;3. Integrated Center for Sciences, Tarumi Station, Ehime University, 3-5-7 Tarumi, Matsuyama, Ehime 790-8566, Japan |
| |
| Abstract: | A series of new 1-aryl-6,7-dihydroxy tetrahydroisoquinolines with several substitution patterns in the 1-aryl group at C-1 were prepared in good yields. The influence of each substituent on the affinity and selectivity for D1 and D2 dopaminergic receptors was studied. Moreover, N-alkyl salts of these tetrahydroisoquinolines were used as starting material to synthesize a series of new 1-aryl-7,8-dihydroxy 3-tetrahydrobenzazepines derivatives with electron-withdrawing substituents at C-2 position by the diastereoselective Stevens rearrangement. The structure-activity relationship of these compounds was explored to evaluate the effect of the functional group at C-2 in benzazepines and the modification in the aryl group at the isoquinoline C-1 position towards the affinity and selectivity for the mentioned receptors. The 1-aryl-6,7-dihydroxy tetrahydroisoquinoline 4c shows significant affinity towards D2 receptor, with Ki value of 31 nM. This significant affinity can be attributed to the presence of a thiomethyl group, and it is the most active 1-aryl-6,7-dihydroxy tetrahydroisoquinoline derivative reported to date. |
| |
| Keywords: | Tetrahydroisoquinolines 3-Tetrahydrobenzazepines Stevens rearrangement Dopamine receptors Binding |
| 本文献已被 ScienceDirect 等数据库收录！ |
|
