4-chloroestrone | 14984-44-2

• 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: 4-chloroestrone
• 英文别名: (8R,9S,13S,14S)-4-chloro-3-hydroxy-13-methyl-7,8,9,11,12,14,15,16-octahydro-6H-cyclopenta[a]phenanthren-17-one
• CAS: 14984-44-2
• 化学式: C₁₈H₂₁ClO₂
• 分子量: 304.817
• InChiKey: XYXJXRSUFSJXNU-QDTBLXIISA-N

物化性质

• 沸点：
  451.2±45.0 °C(Predicted)
• 密度：
  1.248±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  21
• 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：

  4-chloroestrone 在 sodium hydride 、 氨基磺酰氯 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 9.0h， 以8.5%的产率得到4-chloroestrone 3-sulfamate
  参考文献：
  名称：

  Inhibition of estrone sulfatase by aromatase inhibitor-based estrogen 3-sulfamates

  摘要：

  our rationale is based on the finding that estrone 3-sulfamate (EMATE, 2d), a typical estrone sulfatase (ES) inhibitor, can be hydrolyzed and the pharmacological effect of the free estrogen contributes to the bioactivity of the sulfamate. A number of 3-sulfamoylated derivatives of the good aromatase inhibitors, 2- and 4-halogeno (F, Cl, and Br) estrones and their estradiol analogs as well as 6 beta-methyl and phenyl estrones, were synthesized and evaluated as inhibitors of ES in human placental microsomes in comparison with the lead compound EMATE. Among them, 2-chloro- and 2-bromoestrone 3-sulfamates (2b and 2c), along with their estradiol analogs 3b and 3c, were powerful competitive inhibitors with K-i's ranging between 4.0 and 11.3 nM (K-i for EMATE, 73 nM). These four sulfamates as well as the 2-fluoro analogs 2a and 3a inactivated ES in a time-dependent manner more efficiently than EMATE, and 2-halogeno estrone sulfamates 2 also caused a concentration-dependent loss of ES activity. The results may be useful for developing a new class of drugs having a dual function, ES inhibition and aromatase inhibition, for the treatment of breast cancer. (c) 2006 Elsevier Inc. All rights reserved.

  DOI：

  10.1016/j.steroids.2005.12.004
• 作为产物：
  描述：

  4-溴雌酮 在 copper(l) chloride 作用下， 以 二甲基亚砜 为溶剂， 反应 16.0h， 以89%的产率得到4-chloroestrone
  参考文献：
  名称：

  WO2008/124922

  摘要：

  公开号：

文献信息

• Chemical evidence for peroxy radicals intermediacy in copper(II) reaction with hydroperoxides.
  作者：Michel Maumy、Patrice Capdevielle

  DOI：10.1016/s0040-4020(01)87222-7

  日期：1993.8

  of tertiary hydroperoxides by Cu(II) in CH3CN have been encountered : deoxygenation of 4- hydroperoxy cyclohexa 2,5- dienones 1 and 2 brings chemical support to the existence of intermediate peroxy radicals R-OO.1′ and 2′.

  在CH 3 CN中，Cu（II）导致了氢过氧化物叔酸的两个前所未有的分解：4-氢过氧环己基2,5-二烯酮1和2的脱氧为中间过氧自由基R-OO的存在提供了化学支持。1'和2'。
• SUBSTITUTED 16,17-ANNELLATED STERIOD COMPOUNDS FOR USE IN WOMENS HEALTHCARE
  申请人：Dijcks Fredericus Antonius

  公开号：US20100331292A1

  公开（公告）日：2010-12-30

  The present invention relates to substituted steroid compounds having the formula Wherein R 1 is H or halogen; R 2 is H, (1C-4C)alkyl, (1C-4C)acyl, glucuronyl or sulfamoyl; R 3 is H or halogen; R 4 is H, (1C-4C)alkyl, (2C-4C)alkenyl or (2C-4C)alkynyl; R 5 is methyl or ethyl; R 6 is H or methyl; R 7 is H or methyl; R 8 is H or acyl for use in the treatment and prevention of endometriosis, for contraception, for hormonal therapy in perimenopausal and post-menopausal women, for the treatment of osteoporosis and for the treatment uterine fibroids and other menstrual-related disorders, such as dysfunctional uterine bleeding.

  本发明涉及具有以下结构式的取代类固醇化合物 其中R 1 为H或卤素；R 2 为H，(1C-4C)烷基，(1C-4C)酰基，葡萄糖醛酰基或磺酰基；R 3 为H或卤素；R 4 为H，(1C-4C)烷基，(2C-4C)烯基或(2C-4C)炔基；R 5 为甲基或乙基；R 6 为H或甲基；R 7 为H或甲基；R 8 为H或酰基，用于治疗和预防子宫内膜异位症，避孕，围绝经期和绝经后妇女的激素疗法，治疗骨质疏松症以及治疗子宫肌瘤和其他与月经有关的疾病，如功能性子宫出血。
• [EN] SUBSTITUTED 16,17-ANNELLATED STEROID COMPOUNDS FOR USE IN WOMEN'S HEALTHCARE<br/>[FR] COMPOSÉS STÉROÏDES 16,17-ANNELÉS SUBSTITUÉS DESTINÉS À ÊTRE UTILISÉS POUR LA SANTÉ FÉMININE
  申请人：ORGANON NV

  公开号：WO2010142705A1

  公开（公告）日：2010-12-16

  The present invention relates to substituted steroid compounds having the formula (I) Wherein R1 is H or halogen; R2 is H, (1C-4C)alkyl, (1C-4C)acyl, glucuronyl or sulfamoyl; R3 is H or halogen; R4 is H, (1C-4C)alkyl, (2C-4C)alkenyl or (2C-4C)alkynyl; R5 is methyl or ethyl; R6 is H or methyl; R7 is H or methyl; R8 is H or acyl for use in the treatment and prevention of endometriosis, for contraception, for hormonal therapy in perimenopausal and post-menopausal women, for the treatment of osteoporosis and for the treatment uterine fibroids and other menstrual-related disorders, such as dysfunctional uterine bleeding.

  本发明涉及具有以下式（I）的取代类固醇化合物 其中R1为H或卤素；R2为H，（1C-4C）烷基，（1C-4C）酰基，葡萄糖醛酰基或磺酰基；R3为H或卤素；R4为H，（1C-4C）烷基，（2C-4C）烯基或（2C-4C）炔基；R5为甲基或乙基；R6为H或甲基；R7为H或甲基；R8为H或酰基，用于治疗和预防子宫内膜异位症，避孕，围绝经期和绝经后妇女的激素疗法，骨质疏松症的治疗以及子宫肌瘤和其他与月经有关的疾病，如功能性子宫出血。
• 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。