17β-(phenylcarbonyl)-4-aza-5α-androst-1-ene-3-one | 134067-56-4

• 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-(phenylcarbonyl)-4-aza-5α-androst-1-ene-3-one
• 英文别名: 17β-benzoyl-4-aza-5α-androst-1-ene-3-one；17β-benzoyl-4-aza-5α-androst-1-en-3-one；17β-phenylcarbonyl-4-aza-5α-androst-1-en-3-one；(5alpha,17beta)-17-Benzoyl-4-azaandrost-1-en-3-one；(1S,3aS,3bS,5aR,9aR,9bS,11aS)-1-benzoyl-9a,11a-dimethyl-1,2,3,3a,3b,4,5,5a,6,9b,10,11-dodecahydroindeno[5,4-f]quinolin-7-one
• CAS: 134067-56-4
• 化学式: C₂₅H₃₁NO₂
• 分子量: 377.527
• InChiKey: ZYTQEOWFSVTRLX-QKONGSNMSA-N

物化性质

• 沸点：
  557.0±50.0 °C(Predicted)
• 密度：
  1.120±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  28
• 可旋转键数：
  2
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  46.2
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  苯基氯化镁 、 (4aR,4bS,6aS,7S,9aS,9bS,11aR)-S-pyridin-2-yl 4a,6a-dimethyl-2-oxo-2,4a,4b,5,6,6a,7,8,9,9a,9b,10,11,11a-tetradecahydro-1H-indeno[5,4-f]quinoline-7-carbothioate 在 盐酸 作用下， 以 四氢呋喃 、 水 为溶剂， 以77%的产率得到17β-(phenylcarbonyl)-4-aza-5α-androst-1-ene-3-one
  参考文献：
  名称：

  Use of 17B-acyl-4-aza-5alpha-androst-1-en-3-ones for the preparation of a medicament for the prevention of prostatic carcinoma

  摘要：

  17β-Acyl-4-aza-5α-androst-1-ene-3-ones的化学式为：其中R从氢、甲基和乙基中选择，R²是单环芳基，可选含有1个或更多1-2个碳原子的较低烷基取代基和/或1个或更多卤素(Cl或Br)取代基；而R'、R''和R'''各自选择自氢和甲基，上述化合物的药物配方作为睾酮5α-还原酶抑制剂具有活性，因此可用于预防前列腺癌。

  公开号：

  EP0547690A1

文献信息

• A new general method for preparation of N-methoxy-N-methylamides. Application in direct conversion of an ester to a ketone
  作者：J.Michael Williams、Ronald B. Jobson、Nobuyoshi Yasuda、George Marchesini、Ulf-H. Dolling、Edward J.J. Grabowski

  DOI：10.1016/0040-4039(95)01089-z

  日期：1995.7

  The reaction of an ester with N,O-dimethylhydroxylamine and a suitable organomagnesium reagent or lithium amide base provides a general method for the preparation of N-methoxy-N-methylamides. Application in the direct conversion of a highly hindered ester to a ketone, the azasteroid 5α-reductase inhibitor MK-0434, is described.

  酯与N，O-二甲基羟胺和合适的有机镁试剂或氨基锂锂的反应提供了制备N-甲氧基-N-甲基酰胺的一般方法。描述了氮杂类固醇5α-还原酶抑制剂MK-0434在将高度受阻的酯直接转化为酮中的应用。
• Substituted 4-aza-5.alpha.-androstan-ones as 5.alpha.-reductase
  申请人：Merck & Co., Inc.

  公开号：US05693809A1

  公开（公告）日：1997-12-02

  Described are new 16-substituted and 7,16-disubstituted 4-aza-5.alpha.-androstan-3-ones and related compounds as 5.alpha.-reductase inhibitors.

  描述了新的16-取代和7,16-二取代的4-aza-5.alpha.-雄烷-3-酮及相关化合物，作为5.alpha.-还原酶抑制剂。
• Method of treatment for benign prostatic hyperplasia
  申请人：Merck & Co., Inc.

  公开号：US05753641A1

  公开（公告）日：1998-05-19

  Disclosed is an improved treatment for men with benign prostatic hyperplasia (BPH), involving combination therapy of a 5.alpha.-reductase inhibitor, e.g. a 17.beta.-substituted 4-azasteroid, a 17.beta.-substituted non-azasteroid, 17.beta.-acyl-3-carboxy-androst-3,5-diene, benzoylaminophenoxybutanoic acid derivative, fused benz(thio)amide or cinnamoylamide derivative, aromatic 1,2-diethers or thioethers, aromatic ortho acylaminophenoxy alkanoic acids, ortho thioalkylacylaminophenoxy alkanoic acids, pharmaceutically acceptable salts and esters thereof, and particularly finasteride, in combination with an .alpha..sub.1 -adrenergic receptor blocker, i.e., terazosin. The combination provides therapy at the molecular level for the underlying cause of the disease as well as providing symptomatic relief. Pharmaceutical compositions useful for treatment are also disclosed.

  本文揭示了一种改进的治疗方法，用于治疗患有良性前列腺增生（BPH）的男性，涉及联合疗法，包括5α-还原酶抑制剂，例如17β-取代的4-氮杂类固醇，17β-取代的非氮杂类固醇，17β-酰基-3-羧基-雄烯-3,5-二烯，苯甲酰氨基苯氧丁酸衍生物，融合苯基（硫）酰胺或肉桂酰胺衍生物，芳香族1,2-二醚或硫醚，芳香族邻位酰胺基苯氧烷酸，邻位硫烷基酰胺基苯氧烷酸，其药用盐和酯，特别是非那司丁（finasteride），与α1-肾上腺能受体阻滞剂，即特拉唑辛（terazosin）结合。该组合提供了治疗疾病潜在病因的分子水平治疗，同时提供了症状缓解。还揭示了用于治疗的药物组合物。
• Use of 17B-acyl-4-aza-5alpha-androst-1-en-3-ones for the preparation of a medicament for the prevention of prostatic carcinoma
  申请人：MERCK & CO. INC.

  公开号：EP0547690A1

  公开（公告）日：1993-06-23

  17β-Acyl-4-aza-5α-androst-1-ene-3-ones of the formula: wherein R isselected from hydrogen, methyl and ethyl and R² ismonocyclic aryl optionally containing 1 or more lower alkyl substituents of from 1-2 carbon atoms and/or 1 or more halo (Cl or Br) substituents; and R', R'' and R'''are each selected from hydrogen and methyl and pharmaceutical formulation of the above compounds are active as testosterone 5α-reductase inhibitors and thus are useful for the prevention of prostatic carcinoma.

  17β-Acyl-4-aza-5α-androst-1-ene-3-ones的化学式为：其中R从氢、甲基和乙基中选择，R²是单环芳基，可选含有1个或更多1-2个碳原子的较低烷基取代基和/或1个或更多卤素(Cl或Br)取代基；而R'、R''和R'''各自选择自氢和甲基，上述化合物的药物配方作为睾酮5α-还原酶抑制剂具有活性，因此可用于预防前列腺癌。
• 17.beta.-acyl-4-aza-5.alpha.-androst-1-ene-3-ones as 5.alpha.-reductase
  申请人：Merck & Co., Inc.

  公开号：US05049562A1

  公开（公告）日：1991-09-17

  17.beta.-Acyl-4-aza-5.alpha.-androst-1-ene-3-ones of the formula ##STR1## wherein R is selected from hydrogen, methyl and ethyl and R.sup.2 is monocyclic aryl optionally containing 1 or more lower alkyl substituents of from 1-2 carbon atoms and/or 1 or more halo (Cl or Br) substituents; and R', R" and R'" are each selected from hydrogen and methyl and pharmaceutical formulation of the above compounds are active as testosterone 5.alpha.-reductase inhibitors and thus are useful for treatment of acne, seborrhea, female hirsutism, androgenic alopecia, prostatic carcinoma and benign prostatic hypertrophy.

  17-beta-酰基-4-氮杂-5-α-雄烷-1-烯-3-酮的分子式为##STR1##其中R可选自氢、甲基和乙基，R.sup.2是单环芳基，可选含有1个或多个1-2个碳原子的较低烷基取代基和/或1个或多个卤素(Cl或Br)取代基；R'、R"和R'"各自选自氢和甲基，上述化合物的药物制剂作为睾酮5-α-还原酶抑制剂具有活性，因此可用于治疗痤疮、脂溢性皮炎、女性多毛症、雄激素性秃发、前列腺癌和良性前列腺肥大。