Antidopaminergic effects of the stereoisomers of N-[(1-alkyl-2- pyrrolidinyl)methyl]-5-sulfamoylbenzamides and -2,3-dihydrobenzofuran-7-carboxamides

J Med Chem. 1991 Jan;34(1):261-7. doi: 10.1021/jm00105a041.


The stereoisomers of some N-[(1-alkyl-2-pyrrolidinyl)methyl]-5- sulfaoylbenzamides (3-8) and -2,3-dihydrobenzofuran-7-carboxamides (9-18) were prepared to compare their dopamine D2 receptor binding affinities (in vitro) and inhibitory effects on apomorphine-induced hyperactivity (in vivo). In the 1-ethyl substituted compounds of the two series, the stereoisomers with S absolute configuration at the 2-position of the pyrrolidine moiety (S enantiomer 3 and 2S diastereomers 9 and 10) were more potent in both of the above activities than those with R absolute configuration (R enantiomer 4 and 2R diastereomers 11 and 12, respectively), whereas the R enantiomer (8) was more potent than the S enantiomer (7) in the 1-n-hexyl-substituted-benzamides and the 2R diastereomers (15, 16, and 18) were more potent than the 2S diastereomers (13, 14, and 17) in the 1-n-butyl- and 1-n-hexyl-2,3-dihydrobenzofuran-7-carboxamides. It was found that the stereospecificity of the compound activities altered from the S configuration to the R configuration as the 1-alkyl side chain became longer in the two series. How these stereoisomers meet the configurational requirements to interact with the dopamine D2 receptors is also discussed.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Benzamides / chemical synthesis*
  • Benzamides / chemistry
  • Benzamides / pharmacology
  • Corpus Striatum / metabolism
  • Dopamine Antagonists*
  • Indicators and Reagents
  • Molecular Conformation
  • Molecular Structure
  • Motor Activity / drug effects*
  • Optical Rotation
  • Rats
  • Receptors, Dopamine / drug effects*
  • Receptors, Dopamine / metabolism
  • Receptors, Dopamine D2
  • Spiperone / metabolism
  • Stereoisomerism
  • Structure-Activity Relationship


  • Benzamides
  • Dopamine Antagonists
  • Indicators and Reagents
  • Receptors, Dopamine
  • Receptors, Dopamine D2
  • Spiperone