ABSTRACT
This chapter explores the effects that some simple chemical modifications of the basic structure of estradiol can have on estrogenic activity. The attempt is to establish a preliminary basis for structural prediction using molecular modeling, and the consequent correlation with some biological results such as gene induction, as well as the preeminent binding to the estrogen receptor. The correlation of these structures with binding activity and gene induction is poorly understood. However, it should be noted that, although estrogen receptor allows large flexibility in binders, some minimum requirements are essential; thus, minor changes to key molecular areas may have a dramatic effect in estrogen activity. While the repositioning of the hydroxyl group to the C4 location to produce caused very little skeletal change, overall gene induction was turned off despite the fact that receptor binding was better than for isomer. The ultimate goal of these studies is to achieve enough refinement for the theoretical calculation of activity using molecular modeling.
