QSAR, diagnostic statistics and molecular modelling of 1,4-dihydropyridine calcium antagonists: a difficult road...

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.