NMDA-NR2B subtype selectivity of stereoisomeric 2-(1,2,3,4-tetrahydro-1-isoquinolyl)ethanol derivatives |
| |
| Authors: | Höfner Georg Hoesl Cornelia E Parsons Chris Quack Günther Wanner Klaus T |
| |
| Institution: | 1. Department Pharmazie-Zentrum für Pharmaforschung, Ludwig-Maximilians-Universität München, Butenandtstr. 5-13, D-81377 München, Germany;2. Merz Pharma. GmbH & Co. KGaA, Eckenheimer Landstr. 100–104, D-60318 Frankfurt am Main, Germany;1. Department of Discovery Chemistry, Bristol-Myers Squibb Pharmaceutical Research and Development, 5 Research Parkway, Wallingford, CT 06492, United States;2. Preclinical Candidate Optimization, Bristol-Myers Squibb Pharmaceutical Research and Development, 5 Research Parkway, Wallingford, CT 06492, United States;3. Department of Virology, Bristol-Myers Squibb Pharmaceutical Research and Development, 5 Research Parkway, Wallingford, CT 06492, United States;1. LGCR SMRPD Chemical Research, Sanofi US, 153-1-122, 153 2nd Ave, Waltham, MA 02451, USA;2. Sanofi US, Route 202-206, PO Box 6800, Bridgewater, NJ 08807, USA;3. Sanofi R&D, 1 Avenue Pierre Brossolette, Chilly-Mazarin, France;4. Sanofi R&D, Deutschland GmbH, Industriepark Hoechst, Frankfurt, Germany;1. State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 ZuChongZhi Road, Shanghai 201203, China;2. School of Pharmacy, Xinxiang Medical University, 601 Jisui Avenue, Xinxiang, Henan 453003, China;1. Department of Radiopharmacy, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran;2. Department of Radiology, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran;3. Cardiovascular Research Center, Mazandaran University of Medical Sciences, Sari, Iran |
| |
| Abstract: | Enantiopure 2-(1,2,3,4-tetrahydro-1-isoquinolyl)ethanol derivatives were tested for their affinity to the ifenprodil binding site of the NMDA receptor, their potency to inhibit 3H]MK801 binding and their NMDA-NR2B subtype selectivity. The (1S,1'S)-configurated series displayed the highest affinity to the ifenprodil binding site. A reasonable potency and NMDA-NR2B subtype selectivity was found for (1S,1'S)-4c (R1=Me, R2=OMe). A high affinity to HERG K+ channels, however, suggests that (1S,1'S)-4c may involve an increased risk of cardiovascular side effects. |
| |
| Keywords: | |
| 本文献已被 ScienceDirect PubMed 等数据库收录！ |
|
