16-hydroxymethylene-3-benzyloxyestra-1,3,5(10)-trien-17-one | 444196-21-8

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 类固醇和类固醇衍生物
• 英文名称: 16-hydroxymethylene-3-benzyloxyestra-1,3,5(10)-trien-17-one
• 英文别名: 16-hydroxymethylene-3-O-benzylestrone；3-O-benzyl-16-hydroxymethyleneestrone；DSF 03091；(8R,9S,13S,14S,16Z)-16-(hydroxymethylidene)-13-methyl-3-phenylmethoxy-6,7,8,9,11,12,14,15-octahydrocyclopenta[a]phenanthren-17-one
• CAS: 444196-21-8
• 化学式: C₂₆H₂₈O₃
• 分子量: 388.507
• InChiKey: HDMWGOQTHRGNES-ROFUIQCYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.8
• 重原子数：
  29
• 可旋转键数：
  3
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  46.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  16-hydroxymethylene-3-benzyloxyestra-1,3,5(10)-trien-17-one 在 5percent Pd/C 吡啶 、 chromium(VI) oxide 、 盐酸 、 lithium aluminium tetrahydride 、 硫酸 、 氢气 、 potassium carbonate 作用下， 以 四氢呋喃 、 甲醇 、 乙醚 、 乙醇 、 丙酮 为溶剂， 50.0 ℃ 、101.33 kPa 条件下， 反应 77.75h， 生成 3,17beta-Dihydroxyestra-1,3,5(10)-trien-16alpha-carboxylic acid
  参考文献：
  名称：

  Estradiol-16α-carboxylic Acid Esters as Locally Active Estrogens

  摘要：

  We attempted to design analogues of estradiol to act as locally active estrogens without significant systemic action. We synthesized a series of 16a-carboxylic acid substituted steroids and their esters and tested their action in several assays of estrogenic action, including estrogen receptor (ER) binding, estrogenic potency in Ishikawa cells (human endometrial carcinoma), rat uterine weight (systemic action), and mouse vaginal reductases (local action). All of the estradiol substituted carboxylic acids (formic, acetic and propionic acids) were devoid of estrogenic action. To the contrary, many of the esters had marked estrogenic potency in the receptor and the Ishikawa assays. The esters of the 16 alpha -formic acid series had the highest ER affinity with little difference between the straight-chain alcohol esters (from methyl to n-butyl). However, estrogenic action in the Ishikawa assay decreased precipitously with esters longer than the ethyl ester. This decrease correlated well with the increased rate of esterase hydrolysis of longer esters as determined in incubations with rat hepatic microsomes. The most promising candidates, the methyl, ethyl, and fluoroethyl esters of the formate series, were tested for systemic and local action in the in vivo models. All three, especially the fluoroethyl ester, showed divergence between systemic and local estrogenic action. These metabolically labile estrogens will be extremely useful for the therapeutic treatment of the vaginal dyspareunia of menopause in women for whom systemic estrogens are contraindicated.

  DOI：

  10.1021/jm000523h
• 作为产物：
  描述：

  雌酚酮 在 potassium tert-butylate 、 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 2.83h， 生成 16-hydroxymethylene-3-benzyloxyestra-1,3,5(10)-trien-17-one
  参考文献：
  名称：

  E环修饰的类固醇作为17β-羟基类固醇脱氢酶1型的新型有效抑制剂。

  摘要：

  17β-羟基类固醇脱氢酶（17beta-HSDs）是一类重要的类固醇生成酶，可调节活性雌激素和雄激素的生物利用度，并且仍是相对未开发的治疗靶标。根据我们的研究和其他研究，E环修饰的类固醇被确定为设计17beta-HSD 1型抑制剂的有用模板，17β-HSD类型1是一种将雌酮转化为雌二醇的酶。讨论了一系列新的N-和C-取代的1,3,5（10）-雌三烯-[17,16-c]-吡唑的合成及生物学评估，以及相应的SAR。在N-烷基化的类似物中，最有效的抑制剂是1'-甲氧基乙基衍生物41，在T47-D人乳腺癌细胞中的IC（50）为530 nM。测定了1'-异丁基衍生物的X射线晶体结构。使用平行合成对模板进行进一步优化，生成了一个C5'连接的酰胺库，其中出现了73个。该吡啶基乙基酰胺的IC（50）为300 nM，其活性为41，表明吡唑侧链中氢键受体基团的重要性。41和73都显示出对2型17beta-HS

  DOI：

  10.1021/jm050348a

文献信息

• [EN] 17BETA-HYDROXYSTEROID DEHYDROGENASE INHIBITORS<br/>[FR] COMPOSE
  申请人：STERIX LTD

  公开号：WO2004085457A3

  公开（公告）日：2005-02-03
• Synthesis and receptor-binding examination of 16-hydroxymethyl-3,17-estradiol stereoisomers
  作者：Pál Tapolcsányi、János Wölfling、George Falkay、Árpád Márki、Renáta Minorics、Gyula Schneider

  DOI：10.1016/s0039-128x(02)00020-x

  日期：2002.6

  The four 16-hydroxymethylestra-1,3,5(10)-triene-3,17-diol isomers were synthesized and tested in a radioligand-binding assay. The estrogen receptor recognizes these compounds, but their relative binding affinities are lower than 2.0% relative to that of the reference molecule estra-1,3,5(10)-triene-3,17beta-diol. The affinities of the tested compounds for the androgen and progesterone receptors are very low (K(i)> 100 microm and 1 microM, respectively). The prepared 16-hydroxymethylestra-1,3,5(10)-triene-3,17-diol isomers are therefore estrogen receptor-selective molecules.
• Benzothieno and benzofurano annelated estranes
  作者：Masataka Watanabe、Shuntaro Mataka、Thies Thiemann

  DOI：10.1016/j.steroids.2005.06.001

  日期：2005.12

  The preparation of estrone derived benzothieno- and benzofurano fused steroids is described. Keystep is an intramolecular thienyl(/furyl)ene-yne cyclization of 16-ethynyl-17-heterarylestra-1,3,5(10),16-tetraenes. The cyclization was carried out under Pt as well as under Ru catalysis. (c) 2005 Elsevier Inc. All rights reserved.