17-β-[(N-heptyl)-4''-tert-butylbenzamido]-4-methyl-4-aza-5-α-androstan-3-one | 1191100-11-4

• 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: 17-β-[(N-heptyl)-4''-tert-butylbenzamido]-4-methyl-4-aza-5-α-androstan-3-one
• 英文别名: N-[(1S,3aS,3bR,5aR,9aR,9bS,11aS)-6,9a,11a-trimethyl-7-oxo-2,3,3a,3b,4,5,5a,8,9,9b,10,11-dodecahydro-1H-indeno[5,4-f]quinolin-1-yl]-4-tert-butyl-N-heptylbenzamide
• CAS: 1191100-11-4
• 化学式: C₃₇H₅₈N₂O₂
• 分子量: 562.88
• InChiKey: OYPCECAIPQIHMU-FCUNLBQESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  9.3
• 重原子数：
  41
• 可旋转键数：
  9
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.78
• 拓扑面积：
  40.6
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  17β-(N-heptylamino)-4-methyl-4-aza-5α-androstan-3-one 、 对叔丁基苯甲酰氯 在 piperidinomethylpolystyrene resin 作用下， 以 四氢呋喃 为溶剂， 反应 3.0h， 生成 17-β-[(N-heptyl)-4''-tert-butylbenzamido]-4-methyl-4-aza-5-α-androstan-3-one
  参考文献：
  名称：

  Potent and Selective Steroidal Inhibitors of 17β-Hydroxysteroid Dehydrogenase Type 7, an Enzyme That Catalyzes the Reduction of the Key Hormones Estrone and Dihydrotestosterone

  摘要：

  17 beta-Hydroxysteroid dehydrogenase type 7 (17 beta-HSD7) catalyzes the reduction of estrone (E-1) into estradiol (E-2) and of dihydrotestosterone (DHT) into 5 alpha-androstane-3 beta,17 beta-diol (3 beta-diol), therefore modulating the level of mitogenic estrogens and androgens in humans. By classical and parallel chemistry, we generated several 4-methyl-4-aza-5 alpha-androstane derivatives differing in their C-17 substituent: 17 beta-formamide, 17 beta-benzamide, and 17 beta-tertiary amine. Best candidates in each category had demonstrated good inhibitory potency toward the conversion of E-1 into E-2 (IC50 = 189-451 nM) and also toward the conversion of DHT into 3 beta-diol (69-91% at 3 mu M). Inhibition assays with 17 beta-HSD1, 17 beta-HSD5, 5 alpha-reductase (5 alpha-R) 1 and 5 alpha-R2 revealed that 17 beta-HSD7 inhibitors with a 4-methyl-4-aza nucleus were also able to inhibit 5 alpha-Rs but not the other enzymes tested. Two 4-aza-5 alpha-androstane inhibitors were, however, selective and still showed good inhibition of 17 beta-HSD7. First selective and efficient inhibitors of 17 beta-HSD7 are now available for additional mechanistic and therapeutic studies.

  DOI：

  10.1021/jm900921c

文献信息

• Potent and Selective Steroidal Inhibitors of 17β-Hydroxysteroid Dehydrogenase Type 7, an Enzyme That Catalyzes the Reduction of the Key Hormones Estrone and Dihydrotestosterone
  作者：Édith Bellavance、Van Luu-The、Donald Poirier

  DOI：10.1021/jm900921c

  日期：2009.12.10

  17 beta-Hydroxysteroid dehydrogenase type 7 (17 beta-HSD7) catalyzes the reduction of estrone (E-1) into estradiol (E-2) and of dihydrotestosterone (DHT) into 5 alpha-androstane-3 beta,17 beta-diol (3 beta-diol), therefore modulating the level of mitogenic estrogens and androgens in humans. By classical and parallel chemistry, we generated several 4-methyl-4-aza-5 alpha-androstane derivatives differing in their C-17 substituent: 17 beta-formamide, 17 beta-benzamide, and 17 beta-tertiary amine. Best candidates in each category had demonstrated good inhibitory potency toward the conversion of E-1 into E-2 (IC50 = 189-451 nM) and also toward the conversion of DHT into 3 beta-diol (69-91% at 3 mu M). Inhibition assays with 17 beta-HSD1, 17 beta-HSD5, 5 alpha-reductase (5 alpha-R) 1 and 5 alpha-R2 revealed that 17 beta-HSD7 inhibitors with a 4-methyl-4-aza nucleus were also able to inhibit 5 alpha-Rs but not the other enzymes tested. Two 4-aza-5 alpha-androstane inhibitors were, however, selective and still showed good inhibition of 17 beta-HSD7. First selective and efficient inhibitors of 17 beta-HSD7 are now available for additional mechanistic and therapeutic studies.