Napolitano E, Fiaschi R, Carlson K E, Katzenellenbogen J A
Scuola Normale Superiore, Pisa, Italy.
J Med Chem. 1995 Jul 7;38(14):2774-9. doi: 10.1021/jm00014a028.
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.
已合成了四类新的11β-取代雌二醇和雌三醇衍生物（氰基烷基、乙炔基、丙炔基和碘代乙烯基），并评估了它们对雌激素受体的结合亲和力。结合亲和力值表明，雌激素受体对带有11β-基团的雌二醇衍生物具有耐受性，这些基团的大小、刚性和极性都有限。雌二醇衍生物比雌三醇衍生物具有更高的亲和力。讨论了这些药物作为雌激素受体阳性乳腺肿瘤显像剂的潜力。基于本研究及先前报道的一项研究（Napolitano, E.; Fiaschi, R.; Carlson, K. E.; Katzenellenbogen, J. A. 11β-取代雌二醇衍生物，潜在的高亲和力碳-11标记雌激素受体探针：结构-亲和力关系研究。《药物化学杂志》1995年，38卷，429 - 434页）的结果，提出了一种设计高亲和力雌激素受体探针的通用策略。
