Structure-activity relationship studies of N-(9-benzyl)-9- azabicyclo[3.3.1]nonan-3-β-yl benzamide analogues for dopamine D2 and D3 receptors

Robert H. Mach, Philip S. Hammond, Yunsheng Huang, Biao Yang, Yueping Xu, Jason T. Cheney, Rebekah Freeman, Robert R. Luedtke

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A series of benzamide derivatives were prepared in order to determine the nature of the substituent effects in the benzamide aromatic ring on the affinity to dopamine D2 and D3 receptors. Both quantitative structure- activity relationship and molecular modeling (CoMFA) studies were conducted in order to identify the properties of the substituents important for receptor binding. Although traditional QSAR studies provided nearly identical equations for D2 and D3 receptor binding, CoMFA analysis indicated that there are subtle differences in both the steric and electronic properties of the D2 and D3 receptor in the region of the receptor recognizing the benzamide aromatic ring. These data should provide useful information in the design of second-generation analogs possessing a higher affinity for D3 versus D2 receptors.

Original languageEnglish
Pages (from-to)355-373
Number of pages19
JournalMedicinal Chemistry Research
Issue number6
Publication statusPublished - 1 Dec 1999


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