13α-estrone

• 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: 13α-estrone
• 英文别名: 3-hydroxy-13α-estra-1,3,5(10)-trien-17-one；lumiestrone；(8R,9S,13R,14S)-3-hydroxy-13-methyl-7,8,9,11,12,14,15,16-octahydro-6H-cyclopenta[a]phenanthren-17-one
• 化学式: C₁₈H₂₂O₂
• 分子量: 270.371
• InChiKey: DNXHEGUUPJUMQT-XLMAVXFVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  20
• 可旋转键数：
  0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.61
• 拓扑面积：
  37.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  13α-estrone 在 亚硝酸丁酯 、 potassium tert-butylate 作用下， 以 叔丁醇 为溶剂， 反应 18.0h， 生成
  参考文献：
  名称：

  Synthesis and investigation of the anticancer effects of estrone-16-oxime ethers in vitro

  摘要：

  An expanding body of evidence indicates the possible role of estrane derivatives as useful anticancer agents. The aim of this study was to describe the cytotoxic effects of 63 newly synthetized estrone-16-oxime ethers on human cancer cell lines (cervix carcinoma HeLa, breast carcinoma MCF7 and skin epidermoid carcinoma A431), studied by means of the MTT assay. Four of the most promising compounds were selected for participation in additional experiments in order to characterize the mechanism of action, including cell cycle analysis, morphological study and the 5-bromo-2'-deoxyuridine incorporation assay. The cancer selectivity was tested on a noncancerous fibroblast cell line (MRC-5). Since apoptosis and cell cycle disturbance were observed, caspase-3 activities were further assayed for the two most effective agents. These estrone-16-oxime analogs activated caspase-3 and changed the mRNA level expression of endogenous factors regulating the G1-S phase transition (retinoblastoma protein, CDK4 and p16). The repression of retinoblastoma protein was reinforced at a protein level too. These experimental data lead to the conclusion that estrone-16-oxime ethers may be regarded as potential starting structures for the design of novel anticancer agents. (c) 2012 Elsevier Inc. All rights reserved.

  DOI：

  10.1016/j.steroids.2012.10.009
• 作为产物：
  描述：

  estrone 4-fluorophenyl sulfonate 在 吡啶 作用下， 以 甲醇 、 乙腈 为溶剂， 生成 13α-estrone
  参考文献：
  名称：

  某些雌酮芳基和甲基磺酸盐在溶液中的光化学行为：制备和机理研究

  摘要：

  在稳态条件下研究了在氮气氛下不同有机溶剂中雌酮芳基酯和甲基磺酸酯的直接辐照。雌酮衍生物通过涉及 [1;3]-磺酰基迁移的 photo-Fries 重排反应有效地反应，提供邻磺酰基雌酮衍生物和雌酮作为光产物。此外，雌酮和 2-芳基磺酰基雌酮衍生物通过 Norrish I 型反应进行差向异构化。还进行了光反应的化学淬灭和光敏化实验，以建立光反应激发态。同样，还研究了溶剂效应和磺酰基对光反应的性质。

  DOI：

  10.1111/php.13272

文献信息

• Discovery of novel steroidal histamine H 3 receptor antagonists/inverse agonists
  作者：Istvan Ledneczki、Pál Tapolcsányi、Eszter Gábor、János Éles、István Greiner、Éva Schmidt、Zsolt Némethy、Rita Soukupné Kedves、Ottilia Balázs、Viktor Román、György Lévay、Sándor Mahó

  DOI：10.1016/j.bmcl.2017.08.060

  日期：2017.10

  steroid-based histamine H3 receptor antagonists were identified and characterized. Structural moieties of the hit compounds were combined to improve binding affinities which resulted in compound 4 as lead molecule. During the lead optimization due to the versatile modifications of diamino steroid derivatives, several in vitro potent compounds with subnanomolar binding affinities to histamine H3 receptors

  从HTS运动中涌现，鉴定并表征了新型的基于类固醇的组胺H 3受体拮抗剂。结合命中化合物的结构部分以改善结合亲和力，从而产生化合物4作为前导分子。在由于二氨基类固醇衍生物的多用途修饰而导致的前导优化过程中，发现了几种对亚组胺H 3受体具有亲和力的体外有效化合物。通过调节碱度，成功减少了与鼠毒蕈碱受体的不利结合。化合物20在大鼠成虫模型中显示出显着的体内活性，并且将来可以用作药理学工具。
• [EN] INHIBITORS OF 17ß-HSD1, 17ß-HSD3 AND 17ß-HSD10<br/>[FR] INHIBITEURS DE 17SS-HSD1, 17SS-HSD3 ET 17SS-HSD10
  申请人：UNIV LAVAL

  公开号：WO2012129673A1

  公开（公告）日：2012-10-04

  The present application discloses 17β hydroxy steroid dehydrogenase (17β HSD) type 1, 3, 10 inhibitors and use thereof (alone and in combination) in the treatment of cancer and other afflictions. 17β HSDl inhibitors include estradiol derivatives with a nieta-carbamoylbenzyl substituent at C 16. 17β HSD3/HSD10 inhibitors include androsterone derivatives substituted at the C3 position with a sulfonamide piperazine. Also disclosed are compounds that are inhibitors of both 17β HSDl and 17β HSD3 that have a spiro-morpholine substituent at C20.

  该申请公开了17β羟基类固醇脱氢酶（17β HSD）类型1、3、10的抑制剂及其在癌症和其他疾病治疗中的使用（单独和组合使用）。17β HSD1抑制剂包括在C16处带有尼达-氨甲酰苯甲基取代基的雌二醇衍生物。17β HSD3/HSD10抑制剂包括在C3位置用磺胺基哌嗪取代的雄甾酮衍生物。还公开了既是17β HSD1又是17β HSD3抑制剂的化合物，其在C20处带有螺环吗啡基取代基。
• Photo-Fries Rearrangement of Some 3-Acylestrones in Homogeneous Media: Preparative and Mechanistic Studies
  作者：Matías I. Quindt、Gabriel F. Gola、Javier A. Ramirez、Sergio M. Bonesi

  DOI：10.1021/acs.joc.9b00786

  日期：2019.6.7

  series of 3-acylestrones under a nitrogen atmosphere in cyclohexane, acetonitrile (MeCN), and methanol (MeOH) was investigated under steady-state conditions. The molecules underwent the photo-Fries rearrangement, with concomitant homolytic fragmentation of the ester group and [1;3]-acyl migration. This pathway afforded the ortho-acyl estrone derivatives, the main photoproducts, together with estrone. During

  在稳态条件下，研究了在氮气氛下在环己烷，乙腈（MeCN）和甲醇（MeOH）中辐照一系列3-酰基正电子的过程。分子经历了光-弗里斯重排，伴随着酯基的均质裂解和[1; 3]-酰基迁移。该途径提供了邻酰基雌酮衍生物，主要的光产物以及雌酮。在3-苯甲酰基雌酮的辐照过程中，发生了雌酮通过Norrish I型反应的差向异构体，从而提供了荧光增白剂作为光产物。这种光反应涉及类固醇的羰基（C-17）处C-α的断裂。另一方面，在3-乙酰基雌酮的照射过程中发生了邻-区域异构体2-乙酰基雌酮的差向异构化。光-弗里斯反应的N，N，N，N - N-四甲基二氮杂tine二氧化物证实，光反应从单重激发态发生，而Norrish I型反应从三重激发态有效地进行。还研究了溶剂效应以及酰基对光反应的影响。
• Synthesis, Biological Evaluation and Docking Studies of 13-Epimeric 10-fluoro- and 10-Chloroestra-1,4-dien-3-ones as Potential Aromatase Inhibitors
  作者：Rebeka Jójárt、Péter Traj、Édua Kovács、Ágnes Horváth、Gyula Schneider、Mihály Szécsi、Attila Pál、Gábor Paragi、Erzsébet Mernyák

  DOI：10.3390/molecules24091783

  日期：——

  mixture of 10β-fluoroestra-1,4-dien-3-one and 10β-chloroestra-1,4-dien-3-one as the main products. The potential inhibitory action of the 10-fluoro- or 10-chloroestra-1,4-dien-3-one products on human aromatase was investigated via in vitro radiosubstrate incubation. The classical estrane conformation with trans ring anellations and a 13β-methyl group seems to be crucial for the inhibition of the enzyme

  使用 Selectflu 作为试剂，对 13-差向异构雌酮及其 17-脱氧对应物进行氟化。在乙腈或三氟乙酸 (TFA) 中，仅形成 10β-氟雌二醇-1,4-二烯-3-酮。机理研究表明，乙腈中通过 SET 发生氟化，但 TFA 中存在另一种机制。在 TFA 中同时应用 N-氯代琥珀酰亚胺 (NCS) 和 Selectflu，得到 10β-氟代-1,4-二烯-3-酮和 10β-氯代-1,4-二烯-3-酮 1.3:1 的混合物作为主要产品。通过体外放射性底物孵育研究了 10-氟-或 10-氯雌-1,4-二烯-3-酮产品对人芳香酶的潜在抑制作用。具有反式环基团和13β-甲基的经典雌烷构象似乎对于酶的抑制至关重要，而带有13β-甲基的测试化合物仅表现出亚微摩尔或微摩尔IC50值的有效抑制作用。关于生物活性或不活性的分子水平解释，进行了计算模拟。对接研究证实，除了众所周知的 Met374 氢键连接之外，13
• Synthesis and structure–activity relationships of 2- and/or 4-halogenated 13<b><i>β</i></b>- and 13α-estrone derivatives as enzyme inhibitors of estrogen biosynthesis
  作者：Ildikó Bacsa、Bianka Edina Herman、Rebeka Jójárt、Kevin Stefán Herman、János Wölfling、Gyula Schneider、Mónika Varga、Csaba Tömböly、Tea Lanišnik Rižner、Mihály Szécsi、Erzsébet Mernyák

  DOI：10.1080/14756366.2018.1490731

  日期：2018.1.1

  electrophile triggers. Substitutions occurred at positions C-2 and/or C-4. The potential inhibitory action of the halogenated estrones on human aromatase, steroid sulfatase, or 17β-hydroxysteroid dehydrogenase 1 activity was investigated via in vitro radiosubstrate incubation. Potent submicromolar or low micromolar inhibitors were identified with occasional dual or multiple inhibitory properties. Valuable structure-activity

  合成了具有N-卤代琥珀酰亚胺作为亲电子引发剂的A环卤代13α-，13β-和17-脱氧13α-雌酮衍生物。取代发生在位置C-2和/或C-4。通过体外放射性底物孵育研究了卤代雌酮对人芳香酶，类固醇硫酸酯酶或17β-羟基类固醇脱氢酶1活性的潜在抑制作用。潜在的亚微摩尔或低微摩尔抑制剂具有偶发的双重或多重抑制特性。通过获得的抑制数据的比较，建立了重要的构效关系。