17β-hydroxy-7α-phenethylandrost-4-en-3-one | 166819-00-7

• 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-hydroxy-7α-phenethylandrost-4-en-3-one
• 英文别名: (7R,8R,9S,10R,13S,14S,17S)-17-hydroxy-10,13-dimethyl-7-(2-phenylethyl)-1,2,6,7,8,9,11,12,14,15,16,17-dodecahydrocyclopenta[a]phenanthren-3-one
• CAS: 166819-00-7
• 化学式: C₂₇H₃₆O₂
• 分子量: 392.582
• InChiKey: PFTHDRWWQWGYOW-RQYVQDPVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.5
• 重原子数：
  29
• 可旋转键数：
  3
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  37.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  17β-hydroxy-7α-phenethylandrost-4-en-3-one 在 pyridinium chlorochromate 作用下， 以 二氯甲烷 为溶剂， 反应 1.5h， 以100%的产率得到7α-phenethylandrost-4-ene-3,17-dione
  参考文献：
  名称：

  Synthesis, Structure Elucidation, and Biochemical Evaluation of 7.alpha.- and 7.beta.-Arylaliphatic-Substituted Androst-4-ene-3,17-diones as Inhibitors of Aromatase

  摘要：

  The inhibition of aromatase, the cytochrome P450 enzyme complex responsible for the conversion of androgens to estrogens, may be useful for the endocrine treatment of breast cancer. Previously, several 7 alpha-thio-substituted androstenediones have been shown to be potent inhibitors of aromatase. Recent research has focused on producing a more metabolically stable aromatase inhibitor by replacing the carbon-sulfur bond at the 7 alpha-position with a carbon-carbon bond. The new inhibitors, 7 alpha-arylaliphatic-substituted androst-4-ene-3,17-diones (2-4), have alkyl chains of varying length between the steroid and the aryl ring at the 7 alpha-position. The desired targets were synthesized via a 1,6-conjugate addition of the appropriate cuprate to 17 beta-(tert-butyldimethylsiloxy)androsta-4,6-dien-3-one (7). The synthesis also resulted in the formation of the 7 beta-substituted diastereomers (10-11 and 13) as minor products. Initial assignments of the 7 alpha-phenethyl and 7 beta-phenethyl diastereomers were made using highfield 1-D and 2-D NMR studies. The assignment of the diastereomers was confirmed using X-ray crystallography. These compounds were all good inhibitors of aromatase in vitro when assayed using microsomes isolated from human placenta. The 7 alpha-substituted androst-4-ene-3,17-diones (2-4) were effective inhibitors with apparent K(i)s of 13-19 nM. The corresponding 17 beta-hydroxy analogs (8 and 14) and the 7 beta-substituted androstenediones (13 and 16) were less effective inhibitors with apparent K(i)s of 36-44 nM. Thus, a new series of 7 alpha-arylaliphatic-substituted androst-4-ene-3,17-diones has been synthesized, and the compounds are potent competitive inhibitors of aromatase.

  DOI：

  10.1021/jm00015a006
• 作为产物：
  描述：

  (17b)-17-羟基-雄甾-4,6-二烯-3-酮 在 咪唑 、 盐酸 、 tetrakiscopper(I) 、 叔丁基锂 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 18.0h， 生成 17β-hydroxy-7α-phenethylandrost-4-en-3-one
  参考文献：
  名称：

  Synthesis, Structure Elucidation, and Biochemical Evaluation of 7.alpha.- and 7.beta.-Arylaliphatic-Substituted Androst-4-ene-3,17-diones as Inhibitors of Aromatase

  摘要：

  The inhibition of aromatase, the cytochrome P450 enzyme complex responsible for the conversion of androgens to estrogens, may be useful for the endocrine treatment of breast cancer. Previously, several 7 alpha-thio-substituted androstenediones have been shown to be potent inhibitors of aromatase. Recent research has focused on producing a more metabolically stable aromatase inhibitor by replacing the carbon-sulfur bond at the 7 alpha-position with a carbon-carbon bond. The new inhibitors, 7 alpha-arylaliphatic-substituted androst-4-ene-3,17-diones (2-4), have alkyl chains of varying length between the steroid and the aryl ring at the 7 alpha-position. The desired targets were synthesized via a 1,6-conjugate addition of the appropriate cuprate to 17 beta-(tert-butyldimethylsiloxy)androsta-4,6-dien-3-one (7). The synthesis also resulted in the formation of the 7 beta-substituted diastereomers (10-11 and 13) as minor products. Initial assignments of the 7 alpha-phenethyl and 7 beta-phenethyl diastereomers were made using highfield 1-D and 2-D NMR studies. The assignment of the diastereomers was confirmed using X-ray crystallography. These compounds were all good inhibitors of aromatase in vitro when assayed using microsomes isolated from human placenta. The 7 alpha-substituted androst-4-ene-3,17-diones (2-4) were effective inhibitors with apparent K(i)s of 13-19 nM. The corresponding 17 beta-hydroxy analogs (8 and 14) and the 7 beta-substituted androstenediones (13 and 16) were less effective inhibitors with apparent K(i)s of 36-44 nM. Thus, a new series of 7 alpha-arylaliphatic-substituted androst-4-ene-3,17-diones has been synthesized, and the compounds are potent competitive inhibitors of aromatase.

  DOI：

  10.1021/jm00015a006

文献信息

• Synthesis, Structure Elucidation, and Biochemical Evaluation of 7.alpha.- and 7.beta.-Arylaliphatic-Substituted Androst-4-ene-3,17-diones as Inhibitors of Aromatase
  作者：Jill M. O'Reilly、Naiyin Li、William L. Duax、Robert W. Brueggemeier

  DOI：10.1021/jm00015a006

  日期：1995.7

  The inhibition of aromatase, the cytochrome P450 enzyme complex responsible for the conversion of androgens to estrogens, may be useful for the endocrine treatment of breast cancer. Previously, several 7 alpha-thio-substituted androstenediones have been shown to be potent inhibitors of aromatase. Recent research has focused on producing a more metabolically stable aromatase inhibitor by replacing the carbon-sulfur bond at the 7 alpha-position with a carbon-carbon bond. The new inhibitors, 7 alpha-arylaliphatic-substituted androst-4-ene-3,17-diones (2-4), have alkyl chains of varying length between the steroid and the aryl ring at the 7 alpha-position. The desired targets were synthesized via a 1,6-conjugate addition of the appropriate cuprate to 17 beta-(tert-butyldimethylsiloxy)androsta-4,6-dien-3-one (7). The synthesis also resulted in the formation of the 7 beta-substituted diastereomers (10-11 and 13) as minor products. Initial assignments of the 7 alpha-phenethyl and 7 beta-phenethyl diastereomers were made using highfield 1-D and 2-D NMR studies. The assignment of the diastereomers was confirmed using X-ray crystallography. These compounds were all good inhibitors of aromatase in vitro when assayed using microsomes isolated from human placenta. The 7 alpha-substituted androst-4-ene-3,17-diones (2-4) were effective inhibitors with apparent K(i)s of 13-19 nM. The corresponding 17 beta-hydroxy analogs (8 and 14) and the 7 beta-substituted androstenediones (13 and 16) were less effective inhibitors with apparent K(i)s of 36-44 nM. Thus, a new series of 7 alpha-arylaliphatic-substituted androst-4-ene-3,17-diones has been synthesized, and the compounds are potent competitive inhibitors of aromatase.