1,4-Dihydropyridine Antagonist Activities at the Calcium Channel: A Quantitative Structure-Activity Relationship Approach

Academic Article

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 = 0.68π + 2.50σm - 0.47Lmeta - 3.40Blpara + 11.31, which had a correlation coefficient of 0.89. The full data set was best correlated by eq 11, log 1/C = 0.62π + 1.96σm - 0.44Lmeta - 3.26Blpara - 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. © 1988, American Chemical Society. All rights reserved.
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    Digital Object Identifier (doi)

    Author List

  • Coburn RA; Wierzba M; Suto MJ; Solo AJ; Triggle AM; Triggle DJ
  • Start Page

  • 2103
  • End Page

  • 2107
  • Volume

  • 31
  • Issue

  • 11