Patent ID: 6564152
Filing Date: 2003-05-13
Classification: A61K,A61P,C07K,C12Q,G01N,G16C

Abstract:
A method of generating a pharmacophore model for the CYP2D6 inhibitory potency of NK-1 receptor antagonist compounds comprising the steps of(i) generating a set of three-dimensional conformers for each of the compounds in a training set comprising five or more NK-1 antagonists; (ii) correlating each of the compounds of said training set with an observed value for CYP2D6 inhibitory potency; (iii) generating from the conformers of step (i) a set of one or more pharmacophore test models, each said pharmacophore test model comprising three or more of the CYP2D6 enzyme active site features selected from the group consisting of the hydrogen bond donor feature, the hydrogen bond acceptor feature, the hydrophobic region feature, the ionizable region feature and the ring aromatic feature, arranged in three-dimensional space; (iv) calculating the CYP2D6 inhibitory potency for each conformer generated in step (i) towards each of the pharmacophore test models generated in step (iii); (v) calculating the total cost for each pharmacophore test model; and (vi) choosing the lowest cost pharmacophore test model as the pharmacophore model.