PHARMACOPHORE MODELS FOR, METHODS OF SCREENING FOR, AND IDENTIFICATION OF THE CYTOCHROME P-450 INHIBITORY POTENCY OF NEUROKININ-1 RECEPTOR ANTAGONISTS

摘要

The present invention relates to novel screening methods which enable t he selection of neurokinin-1 (NK-1) receptor antagonist compounds which do not possess significant inhibitory potency towards cytochrome P450 enzymes, in particular, CYP2D6. The present invention also relates to a method of generating a pharmacophore model for the CYP2D6 inhibitory activity of NK-1. receptor antagonist compounds; to methods for the discovery of molecules that are potential NK-1 receptors antagonist compounds which do not possess significant inhibitory potency towards the CYP2D6 enzyme; to methods of modeling the features of th e CYP2D6 pharmacophore useful in selecting NK-1 receptor antagonist molecul es which do not possess significant potency towards CYP2D6. Further, the invention also relates to pharmaceutical compositions comprising a NK-1 receptor .antagonist compound which does not possess significant potency towards the CYP2D6 enzym e identified by methods of the invention; to the users of a NK-1 receptor antagonist compound identified by the methods of the invention for the manufacture of medicaments and for the treatment of a condition, a disorder or a disease in a mammal for which an NK-1 antagonist receptor compound identified by the method of t he invention is therapeutically useful.