17β-cyclopropyloxy-4-nitroandrost-4-en-3-one | 161884-70-4

• 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-cyclopropyloxy-4-nitroandrost-4-en-3-one
• 英文别名: 17β-(cyclopropyloxy)-4-nitroandrost-4-en-3-one；17beta-Cyclopropyloxy-4-nitroandrost-4-en-3-one；(8R,9S,10R,13S,14S,17S)-17-cyclopropyloxy-10,13-dimethyl-4-nitro-1,2,6,7,8,9,11,12,14,15,16,17-dodecahydrocyclopenta[a]phenanthren-3-one
• CAS: 161884-70-4
• 化学式: C₂₂H₃₁NO₄
• 分子量: 373.492
• InChiKey: JABJDYMAPPNKSU-KOKPFHDVSA-N

物化性质

• 沸点：
  502.0±50.0 °C(Predicted)
• 密度：
  1.21±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  27
• 可旋转键数：
  2
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.86
• 拓扑面积：
  72.1
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  17β-cyclopropyloxy-4-nitroandrost-4-en-3-one 在 锌 锌 、 乙酸乙酯 、 盐酸 、 乙醚 、 Sodium sulfate-III 、 甲醇 作用下， 以 溶剂黄146 为溶剂， 反应 1.5h， 以to give 4-amino-17-cyclopropyloxyandrost-4-en-3-one (0.59 g), m.p. 100°-102° C. (aqueous methanol)的产率得到4-amino-17-cyclopropyloxyandrost-4-en-3-one
  参考文献：
  名称：

  4-amino-17.beta.-(cyclopropyloxy)androst-4-en-3-one,

  摘要：

  本发明涉及4-氨基-17.beta.-(环丙氧基)雄烯-3-酮，4-氨基-17.beta.-(环丙氨基)雄烯-3-酮及其相关化合物，它们的合成方法，具有C.sub.17-20裂解酶和5α-还原酶抑制活性的药物组合物，本化合物作为C.sub.17-20裂解酶和5α-还原酶抑制剂的用途，以及在雄激素和/或雌激素依赖性疾病的治疗中使用这些化合物的方法，包括良性前列腺增生，乳腺癌和前列腺癌。4-氨基化合物是通过在惰性溶剂中，在强酸的催化下，在适当的反应条件下，将适当的4,5-环氧化合物与叠氮化钠反应制备的。或者，通过在适当的反应条件下，首先硝化然后还原适当的类固醇来制备4-氨基化合物。

  公开号：

  US05486511A1
• 作为产物：
  描述：

  17β-hydroxy-4-nitroandrost-4-en-3-one 在 1,10-phenanthroline-Pd(OAc)2 、 diethylzinc 作用下， 以 乙醚 、 正己烷 、 二氯甲烷 为溶剂， 反应 119.0h， 生成 17β-cyclopropyloxy-4-nitroandrost-4-en-3-one
  参考文献：
  名称：

  Syntheses of Steroidal Vinyl Ethers Using Palladium Acetate−Phenanthroline as Catalyst

  摘要：

  DOI：

  10.1021/jo961182b

文献信息

• Process for the preparation of 4-amino-.DELTA..sup.4 -3-ketosteroids via
  申请人：Merrell Pharmaceuticals Inc.

  公开号：US05965550A1

  公开（公告）日：1999-10-12

  The invention discloses 3-ketosteroids of the following formula used to inhibit steroid C.sub.17-20 lyase: ##STR1## wherein R is OH, C.sub.1 -C.sub.6 alkanoyl, C.sub.1 -C.sub.6 alkanoyloxy, C.sub.1 -C.sub.4 alkanol, COCH.sub.2 OH, CO.sub.2 H, CONR.sub.7 R.sub.8, cyclopropyloxy, cyclopropylamino, acetylthioalkane, 2,2-dimethyldioxolan4-yl, 1,2-dihydroxyethyl and C.sub.1-4 alkylthiol; R.sub.1 is hydrogen, hydroxy or C.sub.1-6 alkyl; R and R.sub.1 together may indicate .dbd.O, that is an oxygen double bonded to the 17 carbon; R.sub.2, R.sub.3, and R.sub.4 are each independently hydrogen or C.sub.1 -C.sub.6 alkyl; R.sub.5 and R.sub.6 are each independently hydrogen or OH; R.sub.5 and R.sub.6 together may indicate .dbd.O, that is an oxygen double bonded to the 11 carbon; R.sub.7 is hydrogen or C.sub.1 -C.sub.8 alkyl; R.sub.8 is C.sub.1 -C.sub.8 alkyl; and with the proviso that, when R is OH, then R.sub.1 is hydrogen; and with the proviso that, when R.sub.5 is OH, then R.sub.6 is hydrogen.

  该发明揭示了以下公式的3-酮类固醇，用于抑制类固醇C.sub.17-20裂解酶：其中R为OH，C.sub.1-C.sub.6烷酰基，C.sub.1-C.sub.6烷酰氧基，C.sub.1-C.sub.4烷醇，COCH.sub.2OH，CO.sub.2H，CONR.sub.7R.sub.8，环丙氧基，环丙基氨基，乙酰硫代烷，2,2-二甲基二氧杂环戊烷-4-基，1,2-二羟乙基和C.sub.1-4烷基硫醇；R.sub.1为氢，羟基或C.sub.1-6烷基；R和R.sub.1一起可能表示.dbd.O，即与第17碳形成氧双键；R.sub.2，R.sub.3和R.sub.4分别独立地为氢或C.sub.1-C.sub.6烷基；R.sub.5和R.sub.6分别独立地为氢或OH；R.sub.5和R.sub.6一起可能表示.dbd.O，即与第11碳形成氧双键；R.sub.7为氢或C.sub.1-C.sub.8烷基；R.sub.8为C.sub.1-C.sub.8烷基；并且在R为OH时，R.sub.1为氢；在R.sub.5为OH时，R.sub.6为氢。
• Process for the preparation of 4-amino- 4-3-ketosteroids via 4-nitro-
  申请人：Merrell Pharmaceuticals Inc.

  公开号：US05750744A1

  公开（公告）日：1998-05-12

  The present invention provides 4-nitro-.DELTA..sup.4 -3-ketosteroids, their use as steroid C.sub.17-20 lyase and 5.alpha.-reductase inhibitors and to a novel process for preparing a compound of the formula: ##STR1## comprising sequentially: a) reacting a starting compound of the formula ##STR2## with an effective amount of a strong base at an elevated or suitable temperature for a time sufficient to create the corresponding thermodynamic dienolate, followed by addition of a neutral nitrating agent to produce the 4-nitro-steroid; and then; b) reacting the 4-nitrosteroid with a suitable reducing agent.

  本发明提供了4-硝基-.DELTA..sup.4-3-酮类固醇，其作为类固醇C.sub.17-20裂解酶和5α-还原酶抑制剂的用途，以及用于制备以下化合物的新方法：##STR1## 包括依次进行：a)将具有以下结构的起始化合物##STR2## 与有效量的强碱在升高或适当的温度下反应足够时间以生成相应的热力学二烯醇负离子，然后加入中性硝化试剂以产生4-硝基类固醇；然后；b)将4-硝基类固醇与适当的还原剂反应。
• Certain 3-ketosteroids used to inhibit steroid 5.alpha.-reductase
  申请人：Merrell Pharmaceuticals, Inc.

  公开号：US05869475A1

  公开（公告）日：1999-02-09

  The invention discloses 3-ketosteroids of the following formula used to inhibit steroid 5.alpha.-reductase: ##STR1## wherein R is OH, C.sub.1 -C.sub.6 alkanoyl, C.sub.1 -C.sub.6 alkanoyloxy, C.sub.1 -C.sub.4 alkanol, COCH.sub.2 OH, CO.sub.2 H, CONR.sub.7 R.sub.8, cyclopropoxy, acetylthioalkane, cyclopylamino, 2-2-dimethyldioxolan-4-yl, 1,2-dihydroxyethyl and C.sub.1-4 alkanethiol; R.sub.1 is hydrogen, hydroxy or C.sub.1-6 alkyl; R.sub.1 and R.sub.2 together may indicate .dbd.O, that is an oxygen double bonded to the 17 carbon; R.sub.2, R.sub.3 and R.sub.4 are each independently hydrogen or C.sub.1-6 alkyl; R.sub.5 and R.sub.6 are each independently hydrogen or OH; R.sub.5 and R.sub.6 together may indicate .dbd.O, that is an oxygen double bonded to the 11 carbon; R.sub.7 is hydrogen or C.sub.1-8 alkyl; R.sub.8 is C.sub.1-8 alkyl; and with the proviso that, when R is OH, then R.sub.1 is hydrogen; and with the proviso that, when R.sub.5 is OH, then R.sub.6 is hydrogen.

  该发明揭示了以下公式的3-酮类固醇，用于抑制类固醇5α-还原酶：##STR1## 其中R为OH，C.sub.1-C.sub.6烷酰基，C.sub.1-C.sub.6烷氧基，C.sub.1-C.sub.4烷醇，COCH.sub.2OH，CO.sub.2H，CONR.sub.7R.sub.8，环丙氧基，乙酰硫代烷基，环戊氨基，2-2-二甲基二氧杂环戊烷-4-基，1,2-二羟乙基和C.sub.1-4烷硫醇；R.sub.1为氢，羟基或C.sub.1-6烷基；R.sub.1和R.sub.2可以共同表示.dbd.O，即与第17碳双键的氧原子；R.sub.2，R.sub.3和R.sub.4各自独立地是氢或C.sub.1-6烷基；R.sub.5和R.sub.6各自独立地是氢或羟基；R.sub.5和R.sub.6可以共同表示.dbd.O，即与第11碳双键的氧原子；R.sub.7为氢或C.sub.1-8烷基；R.sub.8为C.sub.1-8烷基；但是，当R为OH时，R.sub.1为氢；而且，当R.sub.5为OH时，R.sub.6为氢。
• Process for the preparation of 4-amino-.DELTA.4-3-ketosteroids via
  申请人：Merrell Pharmaceuticals Inc.

  公开号：US05990328A1

  公开（公告）日：1999-11-23

  The present invention provides 4-nitro-.DELTA..sup.4 -3-ketosteroids, their use as steroid C.sub.17-20 lyase and 5.alpha.-reductase inhibitors and to a novel process for preparing a compound of the formula: ##STR1## comprising sequentially: a) reacting a starting compound of the formula ##STR2## with an effective amount of a strong base at an elevated or suitable temperature for a time sufficient to create the corresponding thermodynamic dienolate, followed by addition of a neutral nitrating agent to produce the 4-nitrosteroid; and then; b) reacting the 4-nitrosteroid with a suitable reducing agent.

  本发明提供了4-硝基-.DELTA..sup.4 -3-酮类固醇化合物，其用作类固醇C.sub.17-20裂解酶和5α-还原酶抑制剂，以及一种新的制备公式为：##STR1##的化合物的方法，包括顺序地：a)在升高或适当温度下，反应公式为##STR2##的起始化合物与有效量的强碱，足以产生相应的热力学二烯醇负离子，然后添加中性硝化剂以产生4-硝基类固醇；然后；b)用适当的还原剂反应4-硝基类固醇。
• 4-AMINO-17$g(b)-(CYCLOPROPYLOXY)ANDROST-4-EN-3-ONE, 4-AMINO-17$g(b)-(CYCLOPROPYLAMINO)ANDROST-4-EN-3-ONE AND RELATED COMPOUNDS AS C 17-20? LYASE AND 5$g(a)-REDUCTASE INHIBITORS
  申请人：MERRELL DOW PHARMACEUTICALS INC.

  公开号：EP0700400A1

  公开（公告）日：1996-03-13