PMID: 6980283Jun 1, 1982Paper

Absolute stereochemistry and dopaminergic activity of enantiomers of 2,3,4,5-tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine

Journal of Medicinal Chemistry
C KaiserJ Clardy

Abstract

Resolution of the unique dopamine receptor agonist 2,3,4,5-tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine (1) was achieved by a stereospecific multistep conversion of the readily separated enantiomers of its O,O,N-trimethylated precursor 2. The absolute stereochemistry of the antipodes of 2-MeI was determined by single-crystal X-ray diffractometric analysis, thus permitting assignment of the configuration of stereospecifically related 1, as well as that of the synthetic intermediates. High-performance liquid chromatography of diastereoisomeric derivatives was utilized to determine the enantiomeric excess of the R (greater than 97%) and S (greater than 89%) isomers of 1. Examination of the isomers in several in vitro and in vivo tests for both central and peripheral dopaminergic activity revealed that activity resided almost exclusively in the R isomer. The results suggest that the properly oriented 1-phenyl substituent of 1 is important for dopamine-like activity; it may contribute to receptor binding by interaction with a chirally defined accessory site. Configurational and conformational requirements for receptor binding of 1 are considered in relationship to previously described dopaminergic agents. These studies, in acc...Continue Reading

Citations

Jan 1, 1987·Neurochemistry International·P Seeman, D Grigoriadis
Mar 1, 1992·Neurochemistry International·J L NeumeyerR J Baldessarini
Sep 3, 1999·Nuclear Medicine and Biology·J N DaSilvaS Houle
Jun 18, 1999·British Journal of Pharmacology·N G CastroY Aracava
Mar 8, 2016·Biological Psychiatry·Amy F T ArnstenRichard B Mailman
Apr 1, 1985·Medicinal Research Reviews·C Kaiser, T Jain
Apr 1, 1987·Reviews in the Neurosciences·J L Waddington, K M O'Boyle
Dec 1, 2013·Molecular Informatics·Tuomo KalliokoskiAnna Vulpetti
May 15, 2002·The Journal of Pharmacy and Pharmacology·W R WilliamsP J Nicholls
Sep 26, 2019·Current Topics in Medicinal Chemistry·Daniel E FelsingJohn A Allen
Jan 1, 1983·Journal of Neuroscience Research·Y NimitV E Davis
Jul 21, 2021·Nature Chemistry·Ruirui LiDongbing Zhao
Aug 17, 2010·Bioorganic & Medicinal Chemistry·Lisa A BonnerDavid E Nichols

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