The use of aromatase inhibitors as anti-tumor agent for breast cancer has long been recognized, but only aminoglutethimide is currently in clinical use. Based on new research findings, 4-hydroxy-4-androsterone 3,17-dione (4-OHA) has been a model for obtaining newer aromatase inhibitors. A Structural-Activity Relationship study on this compound through preparation of derivatives of the various important positions of 4-OH, could yield better aromatase inhibitors in-vivo. Approaches to the synthesis of potential aromatase inhibitors based on findings by other workers is being proposed. It will involve modification of the structure of 4-androsterone 3, 17-dione; 1,4-androstadiene 3,17-dione 19,6- androstatrien-3,17-dione at positions 4,6,7,10 and 19 and some sort of combinations. The synthesized compounds will be evaluated for aromatase inhibitor activity, mode of inhibition (i.e. whether competitive or non- competitive, reversible or irreversible) their metabolic and distribution profile and their ability to regress mammary cancer in experimental animals.
| Akkani, A; Paterlini, G; Gleason, W B et al. (1997) 6 beta-Propynyl-substituted steroids: mechanism-based enzyme-activated irreversible inhibitors of aromatase. J Med Chem 40:3263-70 |
