PHARMACOLOGICAL DISTRIBUTION DIAGRAMS - A TOOL FOR DE-NOVO DRUG DESIGN

Discriminant analysis applied to SAR studies using topological descrip tors allows us to plot frequency distribution diagrams: a function of the number of drugs within an interval of values of discriminant funct ion vs. these values. We make use of these representations, pharmacolo gical distribution diagrams (PDDs), in structurally heterogeneous grou ps where generally they adopt skewed Gaussian shapes or present severa l maxima. The maxima afford intervals of discriminant function in whic h exists a good expectancy to find new active drugs. A set of beta-blo ckers with contrasted activity has been selected to test the ability o f PDDs as a visualizing technique, for the identification of new beta- blocker active compounds. (C) 1996 by Elsevier Science Inc.