Design, synthesis and evaluation of novel steroid mimics

Steroids ellicit their diverse biol. actions via different functionality located around the periphery of their rigid tetra-cyclic core. For example, estradiol (1) can be viewed as a phenolic and a secondary alc. that are spatially fixed by a central lipophilic scaffold (3). Although steroids are chem. quite simple mols., with relatively few functional groups, their stereochem. and architectural complexity renders them an exceedingly difficult target for chem. synthesis. We will report on a program of work to prep. mimics for both androgenic (5) and estrogenic (4) activators that posess a central dicarbonyl moiety where the opposed dipole moments of the carbonyl groups spacially fix the A and D ring mimics in space. The mols. are simple to prep. and therefore amenable to the generation of a diverse range of compds. for biol. evaluation. The synthesis and comprehensive SAR of both the A and D ring mimics of 4 and 5 will be presented. [on SciFinder(R)]