Synthesis and D2-like binding affinity of 4,5-dihydro-1H-benzo[g]indole-3-carboxamide derivatives as conformationally restricted 5-phenyl-pyrrole-3-carboxamide analogs

Farmaco. 1998 Oct-Nov;53(10-11):684-9. doi: 10.1016/s0014-827x(98)00087-1.

Abstract

A series of 4,5-dihydro-1H-benzo[g]-indole-3-carboxamide derivatives 2a-g were synthesized as conformationally restricted analogs of the dopamine D2-like 5-phenylpyrrole-3-carboxamide ligands and evaluated for their affinity for the dopamine D2-like receptors. In this series, N3-[(1-ethyltetrahydro-1H-2-pyrrolyl)methyl]-4,5-dihydro-1H-benzo[ g]indole- 3-carboxamide (2a) showed the highest affinity for D2-like receptors (IC50 = 160 nM). Replacement of the N-(1-ethyl-2-pyrrolidinyl)methyl side chain with a 2-(N,N-diethylamino)ethyl or a 1-benzyl-4-piperidinyl group (2b, 2d) decreased affinity for the D2-like receptor. The other compounds tested were found to be devoid of D2-like binding affinity.

MeSH terms

  • Animals
  • Benzamides / metabolism
  • Binding, Competitive
  • Dopamine Antagonists / metabolism
  • Indoles / chemical synthesis*
  • Indoles / chemistry
  • Indoles / metabolism
  • Indoles / pharmacology
  • Male
  • Molecular Conformation
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Dopamine D2 / metabolism*
  • Structure-Activity Relationship

Substances

  • Benzamides
  • Dopamine Antagonists
  • Indoles
  • Receptors, Dopamine D2
  • nemonapride