11-BETA-SUBSTITUTED ESTRADIOL DERIVATIVES, POTENTIAL HIGH-AFFINITY CARBON-11-LABELED PROBES FOR THE ESTROGEN-RECEPTOR - A STRUCTURE-AFFINITY RELATIONSHIP STUDY

被引:29
作者
NAPOLITANO, E
FIASCHI, R
CARLSON, KE
KATZENELLENBOGEN, JA
机构
[1] UNIV ILLINOIS, DEPT CHEM, URBANA, IL 61801 USA
[2] SCUOLA NORMALE SUPER PISA, I-56100 PISA, ITALY
[3] UNIV PISA, DIPARTIMENTO CHIM BIOORGAN, I-56126 PISA, ITALY
关键词
D O I
10.1021/jm00003a005
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
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=CH; d, -C=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=CMe, Ph, or cis-CH=CHMe) had uniformly lower RBA values.
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页码:429 / 434
页数:6
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