P-2T PURINOCEPTOR ANTAGONISTS - A QSAR STUDY OF SOME 2-SUBSTITUTED ATP ANALOGS

FPL67085MX represents the first in a class of novel, highly potent and selective P-2T purinoceptor antagonists which are inhibitors of adeno sine diphosphate (ADP)-induced platelet aggregation in-vitro. In an ea rly series of compounds we studied the effect of variation of the aden ine 2-substituent on potency and derived quantitative structure-activi ty relationships (QSARs) between the properties of the molecules and t heir biological activity. This work has recently been revisited using comparative molecular-field analysis (CoMFA) and the comparison of the predictions from the two methods is discussed along with their relati ve merits in terms of compound design. The model suggests that the rec eptor for these molecules has a narrow lipophilic cleft, which is occu pied by the adenine 2-substituent.