Napolitano E, Fiaschi R, Carlson K E, Katzenellenbogen J A
Scuola Normale Superiore, Piazza dei Cavalieri, Pisa, Italy.
J Med Chem. 1995 Feb 3;38(3):429-34. doi: 10.1021/jm00003a005.
In view of their possible development as carbon-11-labeled receptor-based radiotracers for imaging estrogen-responsive breast tumors, we have synthesized a series of estradiols (1), estriols (2), 11 beta-ethylestradiols (3), 11 beta-ethylestriols (4), 11 beta-methoxyestradiols (5), and 11 beta-methoxyestriols (6), differing in the type of substituent R present at the 17 alpha-position (a, -H; b, -CH3; c, -C identical to CH; d, -C identical to CCH3; e, -Ph; f, -CH = CHMe cis), and measured their binding affinity for the estrogen receptor relative to estradiol (RBA). As expected, all the derivatives having an 11 beta-ethyl substituent have good binding properties (3a-d, 4a-d, RBA (25 degrees C): 109-3000%), and among them there are several promising candidates for carbon-11 labeling. Moxestrol (RBA (25 degrees C) = 185%) and its corresponding estriol derivative (4c, RBA (25 degrees C) = 20%) were the analogs having the highest affinity in the 11 beta-methoxyestradiol (5a-f) and 11 beta-methoxyestriol (6a-e) series, respectively; other analogs (R = Me, C identical to CMe, Ph, or cis-CH = CHMe) had uniformly lower RBA values.
鉴于它们有可能被开发为用于成像雌激素反应性乳腺肿瘤的基于碳-11标记的受体放射性示踪剂，我们合成了一系列雌二醇（1）、雌三醇（2）、11β-乙基雌二醇（3）、11β-乙基雌三醇（4）、11β-甲氧基雌二醇（5）和11β-甲氧基雌三醇（6），它们在17α-位存在的取代基R的类型上有所不同（a，-H；b，-CH3；c，-C≡CH；d，-C≡CCH3；e，-Ph；f，-CH = CHMe顺式），并测量了它们相对于雌二醇的雌激素受体结合亲和力（相对结合亲和力，RBA）。正如预期的那样，所有具有11β-乙基取代基的衍生物都具有良好的结合特性（3a - d，4a - d，25℃时的RBA：109 - 3000%），其中有几种是进行碳-11标记的有前景的候选物。莫昔芬（25℃时的RBA = 185%）及其相应的雌三醇衍生物（4c，25℃时的RBA = 20%）分别是11β-甲氧基雌二醇（5a - f）和11β-甲氧基雌三醇（6a - e）系列中亲和力最高的类似物；其他类似物（R = Me、C≡CMe、Ph或顺式-CH = CHMe）的RBA值均较低。
