Theoretical conformational studies on some dopamine antagonistic benzamide drugs: 3-pyrrolidyl- and 4-piperidyl derivatives.
Model derivatives of 3-pyrrolidyl- and 4-piperidyl-o-methoxybenzamides, as representatives of neuroleptic substituted benzamide drugs, have been investigated by theoretical conformational analysis. Folded conformers of 2-methoxy-N-(1-methyl-3-pyrrolidyl)benzamide have the lowest energy, but extended conformers are only a few kilocalories per mole less stable. As regards to piperidyl derivative, it has been found that folded conformers are of much higher energy than extended ones. These and previous results are discussed in terms of the pharmacologically active conformers of substituted benzamide drugs and of possible modes of interaction with the dopamine receptor.
D000818:Animals; D001549:Benzamides / Q000138:chemical synthesis* / Q000494:pharmacology; D002151:Calorimetry; D018492:Dopamine Antagonists; D009682:Magnetic Resonance Spectroscopy; D008968:Molecular Conformation; D010880:Piperidines / Q000138:chemical synthesis / Q000494:pharmacology; D011759:Pyrrolidines / Q000138:chemical synthesis / Q000494:pharmacology; D011954:Receptors, Dopamine / Q000378:metabolism; D013329:Structure-Activity Relationship
D001549:Benzamides; D018492:Dopamine Antagonists; D010880:Piperidines; D011759:Pyrrolidines; D011954:Receptors, Dopamine