ABSTRACT
This chapter discusses aromatase mechanism and inhibition and presents the interrelationship between steroidal structure and chemical/biological reactivity, an interrelationship which has been and will continue to be crucial to inhibitor design and mechanistic understanding. Before discussing aromatase inhibition, it seems important to outline current knowledge of aromatase mechanism. Besides the benefits to rational drug design, interest in the elucidation of the mechanism of aromatase has come from the chemical novelty of the androgen to estrogen conversion. Compounds that bind reversibly to the active site of aromatase as steroid substrate analogues, and fail to turn over very rapidly, may be useful inhibitors. The rational design of a new generation of highly specific mechanism-based inhibitors will require detailed understanding of the mechanism of action both of aromatase and of the present group of inhibitors. Potential problems with steroidal inhibitors of aromatase are illustrated by the possibility of interaction with and rogen-transforming enzymes and with androgen receptors.
