17β-(cyclopropyloxy)androst-5-en-3β-ol | 121241-89-2

• 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: 17β-(cyclopropyloxy)androst-5-en-3β-ol
• 英文别名: 17beta-(Cyclopropyloxy)androst-5-en-3beta-ol；(3S,8R,9S,10R,13S,14S,17S)-17-cyclopropyloxy-10,13-dimethyl-2,3,4,7,8,9,11,12,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-3-ol
• CAS: 121241-89-2
• 化学式: C₂₂H₃₄O₂
• 分子量: 330.511
• InChiKey: POSDCFGKQJATFR-QWQRBHLCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  24
• 可旋转键数：
  2
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.91
• 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-(cyclopropyloxy)androst-5-en-3β-ol 在 吡啶 、 乙酸酐 作用下， 生成 3β-(benzenepropionyloxy)-17β-(cyclopropyloxy)androst-5-ene 、 3β-(Cyclopentanepropionyloxy)-17β-(cyclopropyloxy)androst-5-ene
  参考文献：
  名称：

  17.beta.-(cyclopropyloxy)androst-5-en-3.beta.-ol and related compounds

  摘要：

  本发明涉及17.beta.-(环丙氧基)雄甾-5-烯-3.beta.-醇及其相关化合物，以及使用这些化合物治疗雄激素依赖性疾病的方法。这些醚类化合物是通过使用Simmons-Smith反应和适当的乙烯基醚制备的。

  公开号：

  US04891367A1
• 作为产物：
  描述：

  3β-(t-butyldimethylsilyloxy)-17β-ethenyloxyandrost-5-ene 在 四丁基氟化铵 、 diethylzinc 作用下， 生成 17β-(cyclopropyloxy)androst-5-en-3β-ol
  参考文献：
  名称：

  Time-dependent inactivation of steroid C17(20) lyase by 17β-cyclopropyl ether-substituted steroids

  摘要：

  Androstenes bearing a cyclopropyl group attached to the C-17 beta position with a heteroatom linker, designed as mechanism-based inhibitors of steroid C-17(20) lyase, were found to be potent, time-dependent inhibitors of this enzyme.

  DOI：

  10.1016/0960-894x(95)00566-c

文献信息

• 4-amino-17.beta.-(cyclopropyloxy)androst-4-en-3-one,
  申请人：Merrell Dow Pharmaceuticals Inc.

  公开号：US05486511A1

  公开（公告）日：1996-01-23

  This invention is directed to 4-amino-17.beta.-(cyclopropyloxy)androst-4-en-3-one, 4-amino-17.beta.-(cyclopropylylamino)androst-4-en-3-one and related compounds, a process for their synthesis, a pharmaceutical composition having C.sub.17-20 lyase and 5.alpha.-reductase inhibitory activity, the use of the present compounds as C.sub.17-20 lyase and 5.alpha.-reductase inhibitors and also to a method for using such compounds in the treatment of androgen and/or estrogen dependent disorders, including bengin prostatic hyperplasia, breast cancer and prostatic cancer. The 4-amino compounds are prepared by the reaction of the appropriate 4,5-epoxide with sodium azide in an inert solvent in the presence of a catalytic amount of strong acid under appropriate reaction conditions. Alternatively, the 4-amino compounds are prepared by first nitration and then reduction of the appropriate steroid under appropriate reaction conditions.

  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。
• 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4-硝基-.DELTA..sup.4-3-酮类固醇，其用作类固醇C.sub.17-20裂解酶和5α-还原酶抑制剂，并提供了一种制备式化合物的新方法：##STR1## 顺序包括：a)在升高或适宜温度下，使用有效量的强碱与式化合物##STR2##反应，以产生相应的热力学二烯酸盐，然后加入中性硝化剂以产生4-硝基类固醇;然后;b)使用适当的还原剂与4-硝基类固醇反应。
• 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..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.

  本发明揭示了以下式子的3-酮类固醇，用于抑制类固醇C.sub.17-20裂解酶：##STR1## 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，环丙氨基，乙酰硫代烷基，2,2-二甲基二氧杂环己基，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.1一起可以表示.dbd.O，即与17碳形成双键的氧原子; R.sub.2、R.sub.3和R.sub.4各自独立地为氢或C.sub.1-C.sub.6烷基; R.sub.5和R.sub.6各自独立地为氢或OH; R.sub.5和R.sub.6一起可以表示.dbd.O，即与11碳形成双键的氧原子; 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; 前提是，当R为OH时，R.sub.1为氢; 前提是，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。