Calculation of the partition coefficient of N-bridgehead compounds. Comparison of Rekker and Hansch-Leo methods.

Abstract

Partition coeffs. of 56 N-bridgehead compds. [bicyclic and tricyclic pyrido[1,2-a]pyrimidines] were calcd. using Rekker and Hansch-Leo fragment addn. methods. The two methods were evaluated by comparison with exptl. logP values. Limitations of logP prediction were shown in the cases of steric and electronic interactions. The fragment data bases were extended with new fragment values for endocyclic amide groups. Due to the N-bridgehead function this type of amide group is less polar than other amide fragments. On the basis of exptl. data, a ring-closure correction factor was advised for logP calcn. of tricyclic compds. [on SciFinder(R)]