Dimeric 1,4-dihydropyridines as calcium channel antagonists

J Med Chem. 1988 Aug;31(8):1489-92. doi: 10.1021/jm00403a002.

Abstract

A series of 1,n-alkanediylbis(1,4-dihydropyridines) (n = 2, 4, 6, 8, 10, 12) bridged at C3 of 2,6-dimethyl-3-carboxy-5-carbethoxy-4-(3-nitrophenyl)-1,4-dihydropyridin e were synthesized and evaluated in a radioligand binding assay, [3H]nitrendipine in intestinal smooth muscle, as Ca2+ channel ligands. Binding activity was comparable to that of nitrendipine itself but independent of chain length, suggesting the lack of a major binding contribution by the second 1,4-dihydropyridine group. Analogues lacking the second 1,4-dihydropyridine nucleus or possessing an inactive function (4-nitrophenyl) were no less active, confirming that this series of ligands likely does not bridge adjacent 1,4-dihydropyridine receptors of the Ca2+ channel.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Calcium Channel Blockers / chemical synthesis*
  • Calcium Channels
  • Chemical Phenomena
  • Chemistry
  • Dihydropyridines / chemical synthesis*
  • Dihydropyridines / pharmacology
  • Guinea Pigs
  • In Vitro Techniques
  • Male
  • Muscle, Smooth / drug effects
  • Muscle, Smooth / metabolism
  • Receptors, Nicotinic / drug effects
  • Structure-Activity Relationship

Substances

  • Calcium Channel Blockers
  • Calcium Channels
  • Dihydropyridines
  • Receptors, Nicotinic