Synthesis, in vitro dopamine D2 and D3 receptor binding and quantitative structure-activity studies on substituted 2,3-dimethoxy-N-(1- benzyl-4-piperidinyl)benzamides and related compounds

Philip S. Hammond, Jason T. Cheney, Douglas E. Johnston, Richard L. Ehrenkaufer, Robert R. Luedtke, Robert H. Mach

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In an effort to identify potent and selective antagonists at D2-like dopamine receptors, a series of N-substituted 2,3-dimethoxy-N-(1-benzyl-4- piperidinyl)benzamides was prepared. The affinity of each compound for the rat D2 and D3 dopamine receptor has been determined in vitro using radioligand binding protocols with the baculovirus expression system. These studies were designed to explore the effects of steric and electronic modifications to the 4-piperidinyl portion of the benzamides on binding at both receptor sub-types. While the modifications led to compounds of high affinity (K(d) values equal to 1 to 3 nM) at both receptors, significant D3 versus D2 pharmacologic selectivity was not found. Quantitative structure- activity relationships that more precisely define structural modifications that maintain high-affinity are discussed for both the D2 and D3 receptor binding data.

Original languageEnglish
Pages (from-to)35-49
Number of pages15
JournalMedicinal Chemistry Research
Issue number1
Publication statusPublished - 1 Jan 1999


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