Diethyl 3,6-dihydro-2,4-dimethyl-2,6-methano-1,3-benzothiazocine-5,11- dicarboxylates as calcium entry antagonists: new conformationally restrained analogues of Hantzsch 1,4-dihydropyridines related to nitrendipine as probes for receptor-site conformation

J Med Chem. 1987 Apr;30(4):690-5. doi: 10.1021/jm00387a019.

Abstract

The pharmacological activity of rigid analogues of 1,4-dihydropyridine calcium entry antagonists 9-16 is demonstrated by dose-dependent inhibition of the calcium contraction in depolarized rat aortic strips and by a [3H]nitrendipine binding assay in using cardiac sarcolemmal membranes. From the results, a model is proposed as the receptor-bound conformation of the dihydropyridine calcium entry antagonists.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Aorta / drug effects
  • Calcium Channel Blockers / pharmacology*
  • Chemical Phenomena
  • Chemistry
  • Dihydropyridines*
  • Dose-Response Relationship, Drug
  • Heterocyclic Compounds / pharmacology*
  • Ion Channels / drug effects
  • Male
  • Nitrendipine / metabolism
  • Protein Binding / drug effects
  • Pyridines / pharmacology
  • Rats
  • Rats, Inbred Strains
  • Sarcolemma / drug effects
  • Sarcolemma / metabolism
  • Structure-Activity Relationship
  • Swine
  • Terpenes / pharmacology

Substances

  • Calcium Channel Blockers
  • Dihydropyridines
  • Heterocyclic Compounds
  • Ion Channels
  • Pyridines
  • Terpenes
  • 1,4-dihydropyridine
  • Nitrendipine