17a-aza-17-oxo-17a-homoandrosta-3,5-dien-3-oic acid | 1266250-79-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉类
• 英文名称: 17a-aza-17-oxo-17a-homoandrosta-3,5-dien-3-oic acid
• 英文别名: (4aS,4bR,10aR,10bS,12aS)-10a,12a-dimethyl-2-oxo-1,2,3,4,4a,4b,5,9,10,10a,10b,11,12,12a-tetradecahydronaphtho[2,1-f]quinoline-8-carboxylic acid；(4aS,4bR,10aR,10bS,12aS)-10a,12a-dimethyl-2-oxo-3,4,4a,4b,5,9,10,10b,11,12-decahydro-1H-naphtho[2,1-f]quinoline-8-carboxylic acid
• CAS: 1266250-79-6
• 化学式: C₂₀H₂₇NO₃
• 分子量: 329.439
• InChiKey: KUBFMFNUVAVJPX-MWTROVGWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  24
• 可旋转键数：
  1
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.7
• 拓扑面积：
  66.4
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  17a-aza-17-oxo-17a-homoandrosta-3,5-dien-3-oic acid 、 乙酸酐 在 吡啶 、 盐酸 作用下， 以 乙醇 、 二氯甲烷 、 水 为溶剂， 反应 5.0h， 以81.2%的产率得到17a-aza-17a-acetyl-17-oxo-17a-homoandrosta-3,5-dien-3-oic acid
  参考文献：
  名称：

  Synthesis and biological evaluation of novel unsaturated carboxysteroids as human 5α-reductase inhibitors: A legitimate approach

  摘要：

  In the present study, novel steroidal 17a-substituted 3-cyano-17a-aza-D-homo-3,5-androstadien-17-ones (12-19) and 17a-substituted 17-oxo-17a-aza-D-homo-3,5-androstadien-3-oic acids (20-26) were synthesized from dehydroepiandrosterone acetate (6) along with 17-oxo-19-nor-3,5-androstadien-3-oic acid (30) through a multistep synthesis. Compounds were evaluated for their in vitro 5 alpha-reductase inhibitory activity by measuring the conversion of PHI androstenedione in human embryonic kidney (HEK) cells. In vivo 5 alpha-reductase inhibitory activity was also determined using rat prostate weighing method. Compounds 21-23 and 25 showed potent inhibition of 5a-reductase II enzyme with IC50 values of 54.1 +/- 9.5, 22.1 +/- 2.4, 72.8 +/- 2.3 and 26.5 +/- 4.4 nM respectively as compared to Finasteride (30.3 nM) along with a significant (p < 0.05) reduction in rat prostate weight. (C) 2012 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2012.06.026
• 作为产物：
  描述：

  醋酸去氢表雄酮 在 氯化亚砜 、 盐酸羟胺 、 sodium acetate 、 环己酮 、 三溴化磷 、 aluminum isopropoxide 、 溶剂黄146 、 potassium hydroxide 、 sodium hydroxide 作用下， 以 1,4-二氧六环 、 甲醇 、 乙醇 、 水 、 N,N-二甲基甲酰胺 、 甲苯 、 苯 为溶剂， 反应 64.5h， 生成 17a-aza-17-oxo-17a-homoandrosta-3,5-dien-3-oic acid
  参考文献：
  名称：

  Synthesis and biological evaluation of novel unsaturated carboxysteroids as human 5α-reductase inhibitors: A legitimate approach

  摘要：

  In the present study, novel steroidal 17a-substituted 3-cyano-17a-aza-D-homo-3,5-androstadien-17-ones (12-19) and 17a-substituted 17-oxo-17a-aza-D-homo-3,5-androstadien-3-oic acids (20-26) were synthesized from dehydroepiandrosterone acetate (6) along with 17-oxo-19-nor-3,5-androstadien-3-oic acid (30) through a multistep synthesis. Compounds were evaluated for their in vitro 5 alpha-reductase inhibitory activity by measuring the conversion of PHI androstenedione in human embryonic kidney (HEK) cells. In vivo 5 alpha-reductase inhibitory activity was also determined using rat prostate weighing method. Compounds 21-23 and 25 showed potent inhibition of 5a-reductase II enzyme with IC50 values of 54.1 +/- 9.5, 22.1 +/- 2.4, 72.8 +/- 2.3 and 26.5 +/- 4.4 nM respectively as compared to Finasteride (30.3 nM) along with a significant (p < 0.05) reduction in rat prostate weight. (C) 2012 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2012.06.026

文献信息

• Discovery of a novel hybrid from finasteride and epristeride as 5α-reductase inhibitor
  作者：Zhiyi Yao、Yingjun Xu、Minmin Zhang、Sheng Jiang、Marc C. Nicklaus、Chenzhong Liao

  DOI：10.1016/j.bmcl.2010.10.112

  日期：2011.1

  Finasteride and epristeride both inhibit 5 alpha-reductase with high potency via competitive and non-competitive mechanism, respectively. A new hybrid of finasteride and epristeride was designed as a new 5a-reductase inhibitor based on combination principles in medicinal chemistry. Human 5 beta-reductase was chosen as a plausible surrogate of 5 alpha-reductase type II and the results indicate that although the hybrid compound possesses the main bulk of epristeride, its inhibitory mechanism is same as of finasteride. The hybrid turned out to be a potent 5 alpha-reductase inhibitor in low IC50 ranges. Published by Elsevier Ltd.
• Synthesis and biological evaluation of novel unsaturated carboxysteroids as human 5α-reductase inhibitors: A legitimate approach
  作者：Saurabh Aggarwal、Suresh Thareja、T.R. Bhardwaj、Jörg Haupenthal、R.W. Hartmann、Manoj Kumar

  DOI：10.1016/j.ejmech.2012.06.026

  日期：2012.8

  In the present study, novel steroidal 17a-substituted 3-cyano-17a-aza-D-homo-3,5-androstadien-17-ones (12-19) and 17a-substituted 17-oxo-17a-aza-D-homo-3,5-androstadien-3-oic acids (20-26) were synthesized from dehydroepiandrosterone acetate (6) along with 17-oxo-19-nor-3,5-androstadien-3-oic acid (30) through a multistep synthesis. Compounds were evaluated for their in vitro 5 alpha-reductase inhibitory activity by measuring the conversion of PHI androstenedione in human embryonic kidney (HEK) cells. In vivo 5 alpha-reductase inhibitory activity was also determined using rat prostate weighing method. Compounds 21-23 and 25 showed potent inhibition of 5a-reductase II enzyme with IC50 values of 54.1 +/- 9.5, 22.1 +/- 2.4, 72.8 +/- 2.3 and 26.5 +/- 4.4 nM respectively as compared to Finasteride (30.3 nM) along with a significant (p < 0.05) reduction in rat prostate weight. (C) 2012 Elsevier Masson SAS. All rights reserved.