(3R,5S,8R,9S,10S,13S,14S)-3-[(benzylamino)methyl]-3-hydroxy-10,13-dimethyl-2,4,5,6,7,8,9,11,12,14,15,16-dodecahydro-1H-cyclopenta[a]phenanthren-17-one | 210638-17-8

• 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: (3R,5S,8R,9S,10S,13S,14S)-3-[(benzylamino)methyl]-3-hydroxy-10,13-dimethyl-2,4,5,6,7,8,9,11,12,14,15,16-dodecahydro-1H-cyclopenta[a]phenanthren-17-one
• CAS: 210638-17-8
• 化学式: C₂₇H₃₉NO₂
• 分子量: 409.612
• InChiKey: DAMWLTXBCXWMRF-KGURPWLMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  30
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.74
• 拓扑面积：
  49.3
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  乙酰氯 、 (3R,5S,8R,9S,10S,13S,14S)-3-[(benzylamino)methyl]-3-hydroxy-10,13-dimethyl-2,4,5,6,7,8,9,11,12,14,15,16-dodecahydro-1H-cyclopenta[a]phenanthren-17-one 在 piperidinomethyl polystyrene 作用下， 以 二氯甲烷 为溶剂， 反应 2.0h， 生成
  参考文献：
  名称：

  合成和优化的新型3 17β-羟基类固醇脱氢酶抑制剂家族的并行液相化学。

  摘要：

  3型17β-羟基类固醇脱氢酶（17 beta-HSD）将4-雄烯3,17-二酮（Delta（4）-二酮）转化为雄激素睾丸激素。为了生产这种关键的类固醇生成酶的有效抑制剂，我们以较高的收率和平均高效液相色谱（HPLC）纯度为92-94％进行了3beta-取代的雄甾酮（ADT）文库（AD）的并行液相合成。使用并行液相法合成了3个β-氨基甲基ADT衍生物（168个成员）的第一文库（A），其中包括酰胺上的两个分子多样性水平（R（1）和R（2））（方法I）比传统的化学方法花费的时间更少。库A的筛选显示，R（1）（5-8个碳）处的疏水链相对较小，R（2）（1-4个碳）处的疏水取代基较小，提供了最有效的抑制剂。根据这些抑制结果，使用基于清除剂树脂和液相平行化学的改进方法，在很短的时间内生成了3个β-氨基甲基-ADT衍生物（56个成员）的第二个文库（B）。库B比库A产生了更强的抑制剂，并提供了有用的结构-

  DOI：

  10.1021/jm010286y
• 作为产物：
  描述：

  雄诺龙 在 N-甲基吲哚酮 、 molecular sieve 、 四丙基高钌酸铵 、 lithium perchlorate 、 sodium hydride 作用下， 以 二氯甲烷 、 二甲基亚砜 、 乙腈 为溶剂， 反应 168.0h， 生成 (3R,5S,8R,9S,10S,13S,14S)-3-[(benzylamino)methyl]-3-hydroxy-10,13-dimethyl-2,4,5,6,7,8,9,11,12,14,15,16-dodecahydro-1H-cyclopenta[a]phenanthren-17-one
  参考文献：
  名称：

  A solution-phase combinatorial parallel synthesis of 3β-amido-3α-hydroxy-5α-androstane-17-ones

  摘要：

  A two-level library of 3 beta-amido-3 alpha-hydroxy-5 alpha-androstane-17-one compounds was synthesized from a steroid precursor using the solution-phase parallel synthesis. The compounds were easily obtained in high purity by regioselective aminolysis of the oxirane intermediate followed by acylation of the amine. Since oxiranes can be generated from readily available ketones or alkenes, the proposed strategy give access to a large series of compounds. (C) 1998 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0040-4039(98)00772-2

文献信息

• [EN] INHIBITORS OF 17ß-HSD1, 17ß-HSD3 AND 17ß-HSD10<br/>[FR] INHIBITEURS DE 17SS-HSD1, 17SS-HSD3 ET 17SS-HSD10
  申请人：UNIV LAVAL

  公开号：WO2012129673A1

  公开（公告）日：2012-10-04

  The present application discloses 17β hydroxy steroid dehydrogenase (17β HSD) type 1, 3, 10 inhibitors and use thereof (alone and in combination) in the treatment of cancer and other afflictions. 17β HSDl inhibitors include estradiol derivatives with a nieta-carbamoylbenzyl substituent at C 16. 17β HSD3/HSD10 inhibitors include androsterone derivatives substituted at the C3 position with a sulfonamide piperazine. Also disclosed are compounds that are inhibitors of both 17β HSDl and 17β HSD3 that have a spiro-morpholine substituent at C20.

  该申请公开了17β羟基类固醇脱氢酶（17β HSD）类型1、3、10的抑制剂及其在癌症和其他疾病治疗中的使用（单独和组合使用）。17β HSD1抑制剂包括在C16处带有尼达-氨甲酰苯甲基取代基的雌二醇衍生物。17β HSD3/HSD10抑制剂包括在C3位置用磺胺基哌嗪取代的雄甾酮衍生物。还公开了既是17β HSD1又是17β HSD3抑制剂的化合物，其在C20处带有螺环吗啡基取代基。
• Development of 3-substituted-androsterone derivatives as potent inhibitors of 17β-hydroxysteroid dehydrogenase type 3
  作者：René Maltais、Michelle-Audrey Fournier、Donald Poirier

  DOI：10.1016/j.bmc.2011.06.003

  日期：2011.8

  17Beta-hydroxysteroid dehydrogenase type 3 (17 beta-HSD3) is a steroidogenic enzyme that catalyzes the transformation of 4-androstene-3,17-dione (Delta(4)-dione) into androgen testosterone (T). To provide effective inhibitors of androgen biosynthesis, we synthesized two different series (amines and carbamates) of 3 beta-substituted-androsterone derivatives and we tested their inhibitory activity on 17 beta-HSD3. From the results of our structure-activity relationship study, we identified a series of compounds producing a strong inhibition of 17 beta-HSD3 overexpressed in HEK-293 cells (homogenized cells). The most active compound when tested in intact HEK-293 transfected cells, namely (3 alpha,5 alpha)-3-[trans-2,5-dimethyl-4-[2-(trifluoromethyl)phenyl] sulfonyl}piperazin-1-yl]methyl}-3-hydroxyandrostan-17-one (15b), shows an IC50 value of 6 nM, this compound is thus eight times more active than our reference compound D-5-2 (IC50 = 51 nM). This new improved inhibitor did not stimulate the proliferation of androgen-sensitive Shionogi cells, suggesting a non-androgenic profile. Compound 15b is thus a good candidate for further in vivo studies on rodents. (C) 2011 Elsevier Ltd. All rights reserved.