3,17β-dihydroxy-1,3,5-estratriene-17α-acetic acid | 95764-53-7

• 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: 3,17β-dihydroxy-1,3,5-estratriene-17α-acetic acid
• 英文别名: 2-[(8R,9S,13S,14S,17R)-3,17-dihydroxy-13-methyl-7,8,9,11,12,14,15,16-octahydro-6H-cyclopenta[a]phenanthren-17-yl]acetic acid
• CAS: 95764-53-7
• 化学式: C₂₀H₂₆O₄
• 分子量: 330.424
• InChiKey: NQZCBSSZEAIPGQ-NLPMXTIOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  24
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.65
• 拓扑面积：
  77.8
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3,17β-dihydroxy-1,3,5-estratriene-17α-acetic acid 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 、 三氟乙酸 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 58.0h， 生成 N-(6-aminohexyl)-2-[(8R,9S,13S,14S,17R)-3,17-dihydroxy-13-methyl-7,8,9,11,12,14,15,16-octahydro-6H-cyclopenta[a]phenanthren-17-yl]acetamide
  参考文献：
  名称：

  Design, Synthesis, and Biological Evaluation of Ellipticine−Estradiol Conjugates

  摘要：

  Three ellipticine-estradiol conjugates were synthesized in an effort to target the cytotoxicity of ellipticine to estrogen-receptor positive cells. The three conjugates were prepared with linker chains extending from the 17 alpha position of the estradiol to N-2 (compound 3), N-6 (compound 4), and C-9 (compound 5) positions of ellipticine. The ellipticine-estradiol conjugates were evaluated for their abilities to bind to estrogen receptors, to inhibit topoisomerase II, and for their cytotoxicities in human cancer cell lines. Conjugates 3 and 5 displayed weak binding affinities of 0.132 and 0.303 for the estrogen receptor (relative to estradiol = 100), while conjugate 4 did not show any detectable binding to the estrogen receptor. Compound 3 was a moderate inhibitor of topoisomerase II (IC50 24.1 mu M), while 4 and 5 were inactive. Conjugate 3 was consistently more cytotoxic (GI(50) values 1-10 mu M) than compounds 4 and 5 (GI(50) values 10-100 mu M) in a variety of human cancer cell lines, None of the compounds displayed any selectivity for estrogen-receptor positive cell lines, which probably reflects their weak affinities for estrogen receptors.

  DOI：

  10.1021/jm9602930
• 作为产物：
  描述：

  雌酚酮 在 sodium hydroxide 、 锌 作用下， 以 乙醚 、 乙醇 、 苯 为溶剂， 反应 53.0h， 生成 3,17β-dihydroxy-1,3,5-estratriene-17α-acetic acid
  参考文献：
  名称：

  Effect of 17-α-Ethynylestradiol on Activities of Cytochrome P450 2B (P450 2B) Enzymes: Characterization of Inactivation of P450s 2B1 and 2B6 and Identification of Metabolites

  摘要：

  17-α-乙炔雌二醇（17EE）以机制为基础的方式使纯化复溶的大鼠肝细胞色素P450（P450）2B1和人类P450 2B6失活。与17EE共同孵育时，P450 2B2或2B4几乎没有或没有观察到失活。P450 2B1和2B6的失活完全依赖于NADPH和17EE，并遵循伪一级动力学。在30°C下，P450 2B1和2B6的最大失活速率常数分别为0.2和0.03 min⁻¹。对于P450 2B1和2B6，表观K_I分别为11和0.8 μM。将P450 2B1与17EE和NADPH共同孵育20分钟，酶活性损失达75%，同时酶形成还原CO络合物的能力损失为20%至25%。在P450 2B6中，酶活性损失达83%，而CO还原光谱的损失为5%至10%。17EE与P450 2B1和2B6的推算分配比分别为21和13。将另一种底物与17EE同时孵育可保护这两种酶免于失活。对P450 2B1和2B6的放射性标记17EE结合的标记计量比为1.3:1。这些结果表明，17EE以机制为基础的方式使P450 2B1和2B6失活，主要通过17EE的反应性中间体与其Apoprotein结合。对17EE代谢物的分析表明，失活的2B酶主要在于其产生两种P450 2B2或2B4未产生的代谢物的能力。

  DOI：

  10.1124/jpet.300.2.549

文献信息

• Di-steroidal prodrugs of estradiol
  申请人：King Alexander John

  公开号：US20050159399A1

  公开（公告）日：2005-07-21

  The present invention is a di-steroidal prodrug of estradiol having the following formula:

  本发明是一种雌二醇的二类固醇前药，其化学式如下：
• Transdermal estrogen/progestin dosage unit, and fertility control kit comprising said dosage unit.
  申请人：RUTGERS, THE STATE UNIVERSITY OF NEW JERSEY

  公开号：EP0275716A1

  公开（公告）日：1988-07-27

  Transdermal estrogen progestin absorption dosage units have been developed which comprise a backing layer, an adjoining polymer layer is an adhesive layer in which at least minimum effective dose of an estrogen is dissolved or microdispersed. Adhered to the polymer layer is an adhesive layer in which is dissolved and or microdispersed at least minimum doses of progestin. Presently preferred is use of the natural estrogen, 17-beta-estradiol, or ethinyl estradiol or combinations thereof and of the progestin, norethindrone or norgestimate or combinations thereof. The units have biologically acceptable adhesive and polymer layers. The adhesive layer can have dispersed one or more skin permeation enhancing agents. A separating layer can optionally be used in making the dosage units, which separate space the adhesive and polymer layers, which permits estrogen transmission from the polymer layer during treatment. Dosage units are provided which transdermally deliver at least minimum daily doses of the estrogen and progestin for multiple days, such as for one week. The invention also provides a process of fertility control and estrogen replacement therapy using the novel dosage units. Also. the invention provides a fertility control system for fertility control using the novel dosage units.

  已开发出透皮雌激素孕激素吸收剂量单位，它包括一个背衬层、一个相邻的聚合物层和一个粘合层，在粘合层中溶解或微分散了至少最低有效剂量的雌激素。粘附在聚合物层上的是一层粘合剂，其中溶解或微分散有至少最低剂量的孕激素。目前首选的是天然雌激素、17-beta-雌二醇或炔雌醇或其组合，以及孕激素、炔诺酮或炔诺孕酮或其组合。这些单元具有生物可接受的粘合剂层和聚合物层。粘合剂层可分散有一种或多种皮肤渗透促进剂。在制作剂量单位时，可以选择使用分离层，将粘合剂层和聚合物层分开，这样在治疗过程中就可以从聚合物层中透出雌激素。本发明提供的剂量单位可连续多天（如一周）透皮递送至少最低日剂量的雌激素和孕激素。本发明还提供了一种使用新型剂量单位的生育控制和雌激素替代疗法。此外，本发明还提供了一种使用新型剂量单位进行生育控制的生育控制系统。
• Transdermal administration of progesterone, estradiol esters and mixtures thereof
  申请人：ALZA CORPORATION

  公开号：EP0279977A2

  公开（公告）日：1988-08-31

  A transdermal delivery system for the administering of progesterone and an estradiol ester alone or in combination utilizing a polymer matrix having the drug(s) along with a permeation enhancer dispersed throughout.

  一种用于单独或联合使用黄体酮和雌二醇酯的透皮给药系统，利用聚合物基质将药物和渗透促进剂分散在其中。
• Transdermal patches and methods for delivering testosterone
  申请人：THERATECH, INC.

  公开号：EP1604651A1

  公开（公告）日：2005-12-14

  A method of providing testosterone replacement therapy to a woman in need of such therapy comprising applying a testosterone-delivering patch to the skin of said woman which patch transdermally delivers 50 to 500 µg/day of testosterone to the woman.

  一种为需要睾酮替代疗法的妇女提供睾酮替代疗法的方法，包括在该妇女的皮肤上贴上睾酮递送贴片，该贴片经皮向该妇女递送 50 至 500 微克/天的睾酮。
• Method of increasing testosterone and related steroid concentrations in women
  申请人：Unimed Pharmaceuticals, LLC

  公开号：EP2283865A1

  公开（公告）日：2011-02-16

  The present invention relates to methods, kits, combinations, and compositions for treating, preventing or reducing the risk of developing a testosterone deficient disorder, or the symptoms associated with, or related to a testosterone deficient disorder in a female mammal in need thereof. The present invention also relates to a method of administering a steroid in the testosterone synthetic pathway, for example testosterone, to a mammal in need thereof. In addition, the methods, kits, combinations and compositions may be used in conjunction with other pharmaceutical agents effective at treating, preventing, or reducing the risk of developing a testosterone deficient disorder. The methods, kits, combinations and compositions can also be used in conjunction with a pharmacologically effective amount of an estrogenic hormone, for example, estradiol. Furthermore, the methods, kits, combinations and compositions can be used in conjunction with a pharmacologically effective amount of another steroid or pharmaceutical agent that increases serum testosterone levels in a mammal, for example, methyltestosterone.

  本发明涉及治疗、预防或降低雌性哺乳动物睾酮缺乏症或与睾酮缺乏症相关或有关的症状的风险的方法、试剂盒、组合物和组合物。本发明还涉及向需要的哺乳动物施用睾酮合成途径中的类固醇（例如睾酮）的方法。此外，本发明的方法、试剂盒、组合物和组合物还可与其他有效治疗、预防或降低睾酮缺乏症发病风险的药物一起使用。这些方法、试剂盒、组合物和组合物还可与药理有效量的雌激素（例如雌二醇）结合使用。此外，本发明的方法、试剂盒、组合物和组合物还可与药理有效量的另一种可提高哺乳动物血清睾酮水平的类固醇或药剂（例如甲基睾酮）结合使用。