| abstract |
The present invention provides a pharmacophore for designing, screening and identifying inhibitors of CYP17A1 enzymes and CYP19A1 enzymes. The preferred pharmacophore has an atomic spatial arrangement as shown in accompanying drawing 1, wherein: A represents hydrogen bond body; D represents a hydrogen bond donor; and R represents an aromatic ring. Compounds providing a preferred pharmacophore are useful as medicaments in the treatment of cancer, particularly prostate and breast cancer. By way of example, these compounds include N-(4-ethylphenyl)-5-(2-hydroxy-5-methoxybenzoyl)-2-imino-2H-pyran-3-carboxamide and 2-(4-sulfamoylphenoxy)ethyl 2-amino-3-methylbenzoate. Also provided are methods of treating prostate and breast cancer using the compounds of the invention, as well as their salts, solvates, hydrates, primary metabolites and prodrugs. Methods of inhibiting CYP17A1 and CYP19A1, and thereby inhibiting androgenic activity in a subject, are disclosed. The present invention also provides methods for designing, screening and identifying compounds that inhibit CYP17A1 and CYP19A1. |