1,4-Dihydropyridine antagonist activities at the calcium channel: a quantitative structure-activity relationship approach

J Med Chem. 1988 Nov;31(11):2103-7. doi: 10.1021/jm00119a009.

Abstract

The effect of 46 1,4-dihydropyridine-type calcium channel antagonists on the tonic contractile response of longitudinal muscle strips of guinea pig ileum was determined. 2,6-Dimethyl-3,5-dicarbomethoxy-4-phenyl-1,4-dihydropyridine (13) and 13 ortho-, 15 meta-, and seven para-monosubstituted and 10 polysubstituted aromatic derivatives of 13 were studied. The pharmacological activities of the monosubstituted derivatives were best correlated by eq 10, log 1/C = 0.68 pi + 2.50 sigma m -0.47Lmeta -3.40B1para + 11.31, which had a correlation coefficient of 0.89. The full data set was best correlated by eq 11, log 1/C = 0.62 pi + 1.96 sigma m -0.44Lmeta -3.26B1para -1.51Lmeta' + 14.23, which had a correlation coefficient of 0.90. Equations of similar form but involving an ortho steric term were found to correlate the radioligand binding data for this class of compounds.

Publication types

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

MeSH terms

  • Animals
  • Calcium Channels / drug effects*
  • Dihydropyridines / pharmacology*
  • Guinea Pigs
  • In Vitro Techniques
  • Mathematics
  • Muscle Contraction / drug effects
  • Structure-Activity Relationship

Substances

  • Calcium Channels
  • Dihydropyridines
  • 1,4-dihydropyridine