11-BETA-SUBSTITUTED ESTRADIOL DERIVATIVES .2. POTENTIAL CARBON-11-LABELED AND IODINE-LABELED PROBES FOR THE ESTROGEN-RECEPTOR

Four new classes of 11 beta-substituted estradiol and estriol derivatives (cyanoalkyl, ethynyl, propynyl, and iodovinyl) have been synthesized, and their binding affinity for the estrogen receptor has been evaluated. The binding affinity values indicate that the estrogen receptor has tolerance for estradiol derivatives bearing 11 beta-groups whose size, rigidity, and polarity are limited. The estradiol derivatives have higher affinity than the estriol derivatives. The potential of these agents as imaging agent for estrogen receptor-positive breast tumors is discussed. On the basis of the results of this and a previously reported study (Napolitano, E.; Fiaschi, R.; Carlson, K. E.; Katzenellenbogen, J. A. 11 beta-Substituted Estradiol Derivatives, Potential High-Affinity Carbon-11-Labeled Probes for the Estrogen Receptor: A Structure-Affinity Relationship Study. J. Med. Chem. 1995, 38, 429-434), a general strategy for designing high-affinity probes for the estrogen receptor is proposed.