(17β)-3-methoxyestra-1,3,5(10),15-tetraen-17-ol | 17980-88-0

• 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
• 英文名称: (17β)-3-methoxyestra-1,3,5(10),15-tetraen-17-ol
• 英文别名: 3-methoxy-17β-hydroxyestra-1,3,5(10),15-tetraene；Estra-1,3,5(10),15-tetraen-17-ol, 3-methoxy-, (17beta)-；(8R,9S,13S,14S,17S)-3-methoxy-13-methyl-6,7,8,9,11,12,14,17-octahydrocyclopenta[a]phenanthren-17-ol
• CAS: 17980-88-0
• 化学式: C₁₉H₂₄O₂
• 分子量: 284.398
• InChiKey: KAECVEVIXKMEOP-GFEQUFNTSA-N

物化性质

• 熔点：
  152.6-157.2 °C
• 沸点：
  432.7±45.0 °C(Predicted)
• 密度：
  1.130±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  21
• 可旋转键数：
  1
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.58
• 拓扑面积：
  29.5
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (17β)-3-methoxyestra-1,3,5(10),15-tetraen-17-ol 在 草酰氯 、 C₆F₁₃-(CH₂)2-S(O)-CH₃ 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 0.5h， 以80%的产率得到3-methoxy-estra-1,3,5(10),15-tetraen-17-one
  参考文献：
  名称：

  荧光Swern反应。

  摘要：

  DOI：

  10.1021/ja016057i
• 作为产物：
  描述：

  3-methoxy-estra-1,3,5(10),15-tetraen-17-one 在 sodium tetrahydroborate 、 cerium(III) chloride 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 0.5h， 以98%的产率得到(17β)-3-methoxyestra-1,3,5(10),15-tetraen-17-ol
  参考文献：
  名称：

  Use of radical ring opening for introduction of alkyl and substituted alkyl groups with stereochemical control: a synthetic application of cyclopropylcarbinyl radicals

  摘要：

  Cyclopropylcarbinols 2a and 2b (see Scheme I), which are accessible by a number of routes, can be converted into the corresponding radicals 3a and 3b, respectively. These radicals undergo peripheral ring-opening of the cyclopropyl substructure to afford substituted cycloalkenes 4a and 4b. The whole sequence represents a general method for attaching alkyl, and substituted alkyl, groups to an existing cyclic structure, and it can often be carried out with predictable stereo- and regiochemical control. Reaction conditions for the ring-opening depend on the substitution pattern of the cyclopropane: where the non-bridgehead carbon of the cyclopropane carries a strongly electron-withdrawing group, the ring-opening can be done at the reflux temperature of benzene. However, in the absence of such electron-withdrawing groups, a low temperature is best used in order to suppress ring expansion. Various methods that accommodate these requirements are available for generating the radicals.

  DOI：

  10.1021/jo00012a009

文献信息

• 19-NOR-STEROID DERIVATIVES WITH A 15ALPHA, 16ALPHA-METHYLENE GROUP AND A SATURATED 17, 17-SPIRO-LACTONE RING, USE THEREOF, AND MEDICAMENTS CONTAINING SAID DERIVATIVES
  申请人：Klar Ulrich

  公开号：US20100311702A1

  公开（公告）日：2010-12-09

  The 15α,16α-methylene-17-hydroxy-19-nor-17-pregna-4-en-3-one-21-carboxylic acid γ-lactone derivatives of the present invention possess progestational efficacy. They have the general chemical formula I, in which Z is selected from the group comprising an oxygen atom, two hydrogen atoms, NOR and NNHSO 2 R, where R is hydrogen, C 1 -C 10 -alkyl, aryl or C 7 -C 20 -aralkyl, R 4 is hydrogen or halogen, and moreover either: R 6a , R 6b together form methylene or 1,2-ethanediyl or R 6a is hydrogen and R 6b is selected from the group comprising hydrogen, C 1 -C 10 -alkyl, C 2 -C 10 -alkenyl or C 2 -C 10 -alkynyl, and R 7 is selected from the group comprising hydrogen, C 1 -C 10 -alkyl, C 3 -C 6 -cycloalkyl, C 2 -C 10 -alkenyl or C 2 -C 10 -alkynyl, or: R 6a is hydrogen and R 6b and R 7 , together, denote a bond, an oxygen or form methylene, R 18 represents hydrogen or C 1 -C 3 -alkyl and in addition include their solvates, hydrates, stereoisomers and salts.

  本发明的15α,16α-亚甲基-17-羟基-19-去-17-孕烷-4-烯-3-酮-21-羧酸γ-内酯衍生物具有孕酮效应。它们具有通用化学式I，其中Z选自包括氧原子、两个氢原子、NOR和NNHSO2R的群，其中R为氢、C1-C10-烷基、芳基或C7-C20-芳基烷基，R4为氢或卤素，而且还有以下情况之一：R6a，R6b共同形成亚甲基或1,2-乙二基或R6a为氢且R6b选自包括氢、C1-C10-烷基、C2-C10-烯基或C2-C10-炔基的群，R7选自包括氢、C1-C10-烷基、C3-C6-环烷基、C2-C10-烯基或C2-C10-炔基的群，或：R6a为氢且R6b和R7共同表示键合、氧或亚甲基，R18代表氢或C1-C3-烷基，另外还包括它们的溶剂化合物、水合物、立体异构体和盐。
• 15,16-Methylene-17-hydroxy-19-nor-21-carboxylic acid-steroid Y-lactone derivative, use thereof and medicinal products containing the derivative
  申请人：Klar Ulrich

  公开号：US20110015162A1

  公开（公告）日：2011-01-20

  The invention relates to 15,16-methylene-17-hydroxy-19-nor-21-carboxylic acid-steroid γ-lactone derivatives with the general chemical formula I, and R 4 , R 6a , R 6b , R 7 and Z have the meanings stated in claim 1 , and their solvates, hydrates, stereoisomers and salts. The invention further relates to the use of these derivatives for the production of a medicinal product for oral contraception and for the treatment of pre-, peri- and postmenopausal complaints and medicinal products that contain said derivatives. The derivatives according to the invention have a progestational and in preferred cases additionally an antimineralocorticoid and neutral to slightly androgenic action.

  该发明涉及具有通用化学式I的15,16-亚甲基-17-羟基-19-去-21-羧酸类固醇γ-内酯衍生物，其中R4、R6a、R6b、R7和Z的含义如权利要求1所述，并且它们的溶剂化合物、水合物、立体异构体和盐。该发明还涉及利用这些衍生物生产用于口服避孕和治疗围绝经前、围绝经期和绝经后症状的药物产品，以及含有该衍生物的药物产品。根据该发明的衍生物具有孕激素作用，在优选情况下还具有抗矿物皮质激素和中性至轻微雄激素作用。
• 15, 16-METHYLENE-17-(1'-PROPENYL)-17,3'-OXIDOESTRA-4-EN-3-ONE DERIVATIVE , USE THEREOF, AND MEDICAMENT CONTAINING SAID DERIVATIVE
  申请人：Klar Ulrich

  公开号：US20110003779A1

  公开（公告）日：2011-01-06

  The invention relates to 15,16-methylene-17-(1′-propenyl)-17-3′-oxidoestra-4-en-3-one derivatives with the general chemical formula I, where the Z, R 4 , R 6a , R 6b , R 7 and R 18 have the meanings stated in claim 1 , and solvates, hydrates and salts thereof, including all crystal modifications and all stereoisomers of these compounds. The invention also relates to the use of these derivatives for the production of a drug for oral contraception and for the treatment of pre-, peri- and postmenopausal problems and drugs which contain such derivatives, in particular use in the aforesaid indications. The derivatives according to the invention have a progestational and in preferable cases also an antimineralcorticoid and neutral to slight androgenic activity.

  该发明涉及具有一般化学式I的15,16-亚甲基-17-(1'-丙烯基)-17-3'-氧化雌甾-4-烯-3-酮衍生物，其中Z、R4、R6a、R6b、R7和R18具有权利要求1中所述的含义，以及其溶剂化物、水合物和盐，包括这些化合物的所有晶体结构和所有立体异构体。该发明还涉及利用这些衍生物生产口服避孕药和用于治疗围绝经期问题的药物，以及含有这种衍生物的药物，特别是用于上述适应症中。根据本发明的衍生物具有孕激素作用，在优选情况下还具有抗矿皮质激素和中性至轻微雄激素活性。
• 19-NOR-STEROID DERIVATIVES WITH A 15a,16a-METHYLENE GROUP AND A SATURATED 17,17-SPIROLACTONE RING, USE THEREOF, AND MEDICAMENTS CONTAINING SAID DERIVATIVES
  申请人：BAYER INTELLECTUAL PROPERTY GmbH

  公开号：US20130123219A1

  公开（公告）日：2013-05-16

  The 15α,16α-methylene-17-hydroxy-19-nor-17-pregna-4-en-3-one-21-carboxylic acid γ-lactone derivatives of the present invention possess progestational efficacy. They have the general chemical formula I, in which Z is selected from the group comprising an oxygen atom, two hydrogen atoms, NOR and NNHSO 2 R, where R is hydrogen, C 1 -C 10 -alkyl, aryl or C 7 -C 20 -aralkyl, R 4 is hydrogen or halogen, and moreover either: R 6a , R 6b together form methylene or 1,2-ethanediyl or R 6a is hydrogen and R 6b is selected from the group comprising hydrogen, C 1 -C 10 -alkyl, C 2 -C 10 -alkenyl or C 2 -C 10 -alkynyl, and R 7 is selected from the group comprising hydrogen, C 1 -C 10 -alkyl, C 3 -C 6 -cycloalkyl, C 2 -C 10 -alkenyl or C 2 -C 10 -alkynyl, or: R 6a is hydrogen and R 6b and R 7 , together, denote a bond, an oxygen or form methylene, R 18 represents hydrogen or C 1 -C 3 -alkyl and in addition include their solvates, hydrates, stereoisomers and salts.

  本发明的15α，16α-亚甲基-17-羟基-19-去氢-17-孕烷-4-烯-3-酮-21-羧酸γ-内酯衍生物具有孕激素功效。它们具有一般化学式I，其中Z选自包括氧原子、两个氢原子、NOR和NNHSO2R的群，其中R为氢、C1-C10烷基、芳基或C7-C20-芳基烷基，R4为氢或卤素，而且要么：R6a，R6b一起形成亚甲基或1,2-乙二基或R6a为氢，R6b选自包括氢、C1-C10烷基、C2-C10烯基或C2-C10炔基，R7选自包括氢、C1-C10烷基、C3-C6环烷基、C2-C10烯基或C2-C10炔基，或者：R6a为氢，R6b和R7一起表示键，氧或形成亚甲基，R18表示氢或C1-C3烷基，并且还包括它们的溶剂化合物、水合物、立体异构体和盐。
• 19-nor-steroid derivatives with a 15α,16α-methylene group and a saturated 17,17-spirolactone ring, use thereof, and medicaments containing said derivatives
  申请人：Bayer Intellectual Property GmbH

  公开号：US08987239B2

  公开（公告）日：2015-03-24

  The 15α,16α-methylene-17-hydroxy-19-nor-17-pregna-4-en-3-one-21-carboxylic acid γ-lactone derivatives of the present invention possess progestational efficacy. They have the general chemical formula I, in which Z is selected from the group comprising an oxygen atom, two hydrogen atoms, NOR and NNHSO2R, where R is hydrogen, C1-C10-alkyl, aryl or C7-C20-aralkyl, R4 is hydrogen or halogen, and moreover either: R6a, R6b together form methylene or 1,2-ethanediyl or R6a is hydrogen and R6b is selected from the group comprising hydrogen, C1-C10-alkyl, C2-C10-alkenyl or C2-C10-alkynyl, and R7 is selected from the group comprising hydrogen, C1-C10-alkyl, C3-C6-cycloalkyl, C2-C10-alkenyl or C2-C10-alkynyl, or: R6a is hydrogen and R6b and R7, together, denote a bond, an oxygen or form methylene, R18 represents hydrogen or C1-C3-alkyl and in addition include their solvates, hydrates, stereoisomers and salts.

  本发明的15α,16α-亚甲基-17-羟基-19-去-17-孕烷-4-烯-3-酮-21-羧酸γ-内酯衍生物具有孕激素效应。它们具有通用化学式I，其中Z选自包括氧原子、两个氢原子、NOR和NNHSO2R的基团，其中R为氢、C1-C10-烷基、芳基或C7-C20-芳基烷基，R4为氢或卤素，并且还有以下情况之一：R6a，R6b共同形成亚甲基或1,2-乙二基或R6a为氢，R6b选自包括氢、C1-C10-烷基、C2-C10-烯基或C2-C10-炔基的基团，R7选自包括氢、C1-C10-烷基、C3-C6-环烷基、C2-C10-烯基或C2-C10-炔基的基团，或：R6a为氢，R6b和R7共同表示键、氧或形成亚甲基，R18表示氢或C1-C3-烷基，此外还包括它们的溶剂化物、水合物、立体异构体和盐。