QSAR, diagnostic statistics and molecular modelling of 1,4-dihydropyridine calcium antagonists: a difficult road ahead.
Quantitative structure-activity relationships of a series of substituted 1,4-dihydropyridine calcium channel antagonists were studied. The analysis is difficult because of the problem of multicollinearity of substituent parameters, a high-leverage point, and position-dependent grouped observations. Canonical regression appears to be the method of choice. With respect to a maximum activity, it was shown that the following rank order of substituent parameters exists: Lipophilicity approximately ortho-position > inductivity > minimum width > meta-position. The molecular conformation of antagonists does not differ markedly (with exception of nifedipine derivatives and nimodipine), but differences seem to exist between the antagonists and the activator BAY K 8644.
Mager
P P
PP
University of Leipzig, Germany.
Coburn
R A
RA
Solo
A J
AJ
Triggle
D J
DJ
Rothe
H
H
D000818:Animals; D002121:Calcium Channel Blockers / Q000737:chemistry* / Q000494:pharmacology; D004095:Dihydropyridines / Q000737:chemistry* / Q000494:pharmacology; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008958:Models, Molecular; D008968:Molecular Conformation; D013329:Structure-Activity Relationship
D002121:Calcium Channel Blockers; D004095:Dihydropyridines; C038806:1,4-dihydropyridine