MODELING OF THE CCK ANTAGONIST ACTIVITY OF BENZODIAZEPINES ON GASTRINRECEPTORS

The gastrin CCK antagonist activity of 67 benzodiazepines has been stu died by molecular modelling, Construction and optimisation by GenMol a nd MOPAC has allowed us to obtain molecules of absolute minimum energy . Five geometrical parameters and pharmacophores were selected for a p rocessing by neural system. They allow a good prediction of activity o f a compound belonging to this series: the correlation coefficients ar e r = 0.970 for the calculation and r = 0.926 for the prediction. A se cond database, limited to 23 compounds, constituted by a sample of the precedent one, allowed us, by selecting four parameters to obtain a s atisfactory Linear and nonlinear correlation for these compounds. The correlation coefficients obtained by neural system are r = 0.990 for t he calculation and r = 0.981 for the prediction. (C) 1998 Elsevier Sci ence B.V, All rights reserved.