2-乙炔基-alpha-去甲-5-alpha,17-alpha-孕甾-20-炔-2-beta,17-二醇 | 1045-29-0

• 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
• 中文名称: 2-乙炔基-alpha-去甲-5-alpha,17-alpha-孕甾-20-炔-2-beta,17-二醇
• 英文名称: dihydroxy-2β, 17β diethynyl-2α, 17α A-nor(5α)androstane
• 英文别名: 2α,17α-diethynyl-A-nor-5α-androstane-2β,17β-diol；anordiol；α-anordiol；2α,17α-Diethinyl-A-nor-5α-androstan-2β,17β-diol；(2R,3aS,3bS,5aS,6R,8aS,8bR,10aS)-2,6-diethynyl-3a,5a-dimethyl-1,3,3b,4,5,7,8,8a,8b,9,10,10a-dodecahydroindeno[5,4-e]indene-2,6-diol
• CAS: 1045-29-0
• 化学式: C₂₂H₃₀O₂
• 分子量: 326.479
• InChiKey: HUUUMTTWAPMBMU-ZBJWQKIUSA-N

物化性质

• 沸点：
  404.5°C (rough estimate)
• 密度：
  1.0626 (rough estimate)

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  24
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.82
• 拓扑面积：
  40.5
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  2-乙炔基-alpha-去甲-5-alpha,17-alpha-孕甾-20-炔-2-beta,17-二醇 生成 双炔失碳酯
  参考文献：
  名称：

  [EN] ASYMMETRIC SYNTHESIS AND USES OF COMPOUNDS IN DISEASE TREATMENTS
  [FR] SYNTHÈSE ASYMÉTRIQUE ET UTILISATIONS DE COMPOSÉS DANS DES TRAITEMENTS DE MALADIES

  摘要：

  本申请公开了不对称合成公式(I)的对映异构体化合物（例如α-anordrin）或其盐，以及治疗雌激素缺乏症和预防或减轻雌激素缺乏症状的方法和组合物，使用公式(I)的对映异构体化合物（例如α-anordrin）或其盐单独或与至少一种附加剂组合。此外，还提供了在与公式(I)的对映异构体化合物（例如α-anordrin）或其盐的组合疗法中减少附加剂副作用的方法和组合物。

  公开号：

  WO2019042192A1
• 作为产物：
  描述：

  17β-hydroxy-A-nor-5α-androstan-2-one 在 chromium(VI) oxide 作用下， 以 四氢呋喃 、 溶剂黄146 、 二甲基亚砜 为溶剂， 生成 2-乙炔基-alpha-去甲-5-alpha,17-alpha-孕甾-20-炔-2-beta,17-二醇
  参考文献：
  名称：

  Minssen,M.; Jacques,J., Bulletin de la Societe Chimique de France, 1965, p. 71 - 76

  摘要：

  DOI：

文献信息

• [EN] ASYMMETRIC SYNTHESIS AND USES OF COMPOUNDS IN DISEASE TREATMENTS<br/>[FR] SYNTHÈSE ASYMÉTRIQUE ET UTILISATIONS DE COMPOSÉS DANS DES TRAITEMENTS DE MALADIES
  申请人：ZHEJIANG JIACHI PHARMACEUTICAL DEV LTD

  公开号：WO2019042192A1

  公开（公告）日：2019-03-07

  The present application discloses, among other things, asymmetric synthesis a diastereomeric compound of formula (I) (e.g., α-anordrin) or salt thereof. Also provided are methods and compositions for treatment of estrogen deficiency as well as preventing or reducing an estrogen deficiency symptom using a diastereomeric compound of formula (I) (e.g., α-anordrin) or salt thereof alone or in combination with at least one additional agent. Further provided are methods and compositions for reducing a side effect of an additional agent in the context of combination therapy with a diastereomeric compound of formula (I) (e.g., α-anordrin) or salt thereof.

  本申请公开了不对称合成公式（I）的对映异构体化合物（例如α-anordrin）或其盐，以及用于治疗雌激素缺乏症以及预防或减轻雌激素缺乏症状的方法和组合物，使用公式（I）的对映异构体化合物（例如α-anordrin）或其盐单独或与至少一种其他药物联合使用。此外，还提供了在联合治疗中用公式（I）的对映异构体化合物（例如α-anordrin）或其盐减少其他药物的副作用的方法和组合物。
• Predominant contributions of carboxylesterase 1 and 2 in hydrolysis of anordrin in humans
  作者：Jinfang Jiang、Xiaoyan Chen、Dafang Zhong

  DOI：10.1080/00498254.2017.1333658

  日期：2018.5.4

  is post-coital contraceptive drug that is on the market in China for more than 30 years. This study aims to elucidate enzymes involved in anordrin hydrolysis, and to evaluate the significant role of carboxylesterases in anordrin hydrolysis in humans. 2. Human liver and intestinal microsomes, recombinant human carboxylesterase were selected as enzyme sources. In human liver microsomes, intrinsic clearance

  1.炔失碳酯（2 α，17 α -二乙炔-A-NOR-5 α甾-2 β，17 β二醇二丙）是性交后避孕药物是在中国市场超过30年。这项研究旨在阐明参与双炔失碳酯水解的酶，并评估羧酸酯酶在人类双炔失碳蛋白水解中的重要作用。 2.选择人肝和肠微粒体，重组人羧酸酯酶作为酶源。在人肝微粒体中，固有清除率为684±83μL/ min / mg蛋白，大大高于肠道微粒体的值（94.6±13.3μL/ min / mg蛋白）。在人类肝脏中，羧基酯酶（CES）1比CES2具有更大的贡献。 3.使用代表性的酯酶抑制剂进行抑制研究，以确认参与双炔失碳酯水解的酯酶同工型。辛伐他汀强烈抑制双炔失碳素在肝和肠微粒体中的水解过程，IC 50值分别为10.9±0.1和6.94± 0.03μM 。 4.本研究首次研究了双炔失碳酯的水解酶表型。蒽醌主要被CES1和CES2催化，生成主要的活性代谢物，即抗雌二醇。此外，当暴露于
• Pharmacokinetics and pharmacodynamics of anordrin (2α, 17α-diethynyl-A-nor-5α-androstane-2β, 17β-diol diproprionate)
  作者：Robert T. Chatterton、Wlodzimierz Kowalski、Yu-cai Lu、Albert J. Peters

  DOI：10.1016/0039-128x(94)90031-0

  日期：1994.3

  In order to determine the pharmacokinetics of anordrin a dose of 0.2 mg/kg of [3-C-14]anordrin was administered i.v. to 5 cynomolgus monkeys; the same monkeys received the same dose i.m. at a later date. An additional 3 monkeys received 1.0 mg/kg of [3-C-14]anordrin i.m. After administration of the compound, the dipropionate esters of anordrin were rapidly hydrolyzed to the dihydroxy parent compound, anordiol. After i.v. administration, anordrin had a mean residence time (MRT) of 5.0 +/- 1.3 (SE) min. [C-14]Anordiol formed from [C-14]anordrin had an MRT of 139 +/- 27 (SE) min. The metabolic clearance rates (MCR) of anordrin and anordiol were 55 and 34 ml/min.kg, respectively. The apparent volume of distribution at steady state (V-ss) for anordrin was 276 mL/kg, 7.5% of body weight of the animals; anordiol had a much larger V-ss of 4460 mL/kg. The MRT of anordiol after i.m. administration of 1.0 mg/kg of [C-14]anordrin was 26.3 days. An average of 44% of the dose appeared in urine regardless of the route of administration or dose. The MRT values of total radioactivity were the same when calculated from serum or urine after an i.v. dose, but after i.m. administration, values from urine were approximately 60% of that calculated from serum, indicating that products appearing in urine had a shorter MRT than products appearing primarily in feces. A separate group of monkeys was given anordrin i.m. in doses ranging from 0.1 to 0.4 mg/kg on the first day of menses. The regression of length of menstrual cycle on dose was significant (P = 0.004). Control cycle length was 30 days and the response was linear to 76 days with the maximum dose given.
• Minssen,M.; Jacques,J., Bulletin de la Societe Chimique de France, 1965, p. 71 - 76
  作者：Minssen,M.、Jacques,J.

  DOI：——

  日期：——