Allan Gillian M, Vicker Nigel, Lawrence Harshani R, Tutill Helena J, Day Joanna M, Huchet Marion, Ferrandis Eric, Reed Michael J, Purohit Atul, Potter Barry V L
Medicinal Chemistry, Department of Pharmacy and Pharmacology and Sterix Ltd, University of Bath, Claverton Down BA2 7AY, UK.
Bioorg Med Chem. 2008 Apr 15;16(8):4438-56. doi: 10.1016/j.bmc.2008.02.059. Epub 2008 Mar 7.
The 17beta-hydroxysteroid dehydrogenases (17beta-HSDs) catalyze the interconversion between the oxidized and reduced forms of androgens and estrogens at the 17 position. The 17beta-HSD type 1 enzyme (17beta-HSD1) catalyzes the reduction of estrone (E1) to estradiol and is expressed in malignant breast cells. Inhibitors of this enzyme thus have potential as treatments for hormone dependent breast cancer. Syntheses and biological evaluation of novel non-steroidal inhibitors designed to mimic the E1 template are reported using information from potent steroidal inhibitors. Of the templates investigated biphenyl ethanone was promising and led to inhibitors with IC(50) values in the low micromolar range.
17β-羟基类固醇脱氢酶（17β-HSDs）催化雄激素和雌激素在17位的氧化态与还原态之间的相互转化。17β-HSD1型酶（17β-HSD1）催化雌酮（E1）还原为雌二醇，且在恶性乳腺细胞中表达。因此，该酶的抑制剂具有作为激素依赖性乳腺癌治疗药物的潜力。利用强效甾体抑制剂的信息，报道了旨在模拟E1模板的新型非甾体抑制剂的合成及生物学评价。在所研究的模板中，联苯乙酮很有前景，能得到IC（50）值在低微摩尔范围内的抑制剂。
