17-β-(N-nonylamino)-4-methyl-4-aza-5-α-androstan-3-one | 845914-03-6

• 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-nonylamino)-4-methyl-4-aza-5-α-androstan-3-one
• 英文别名: (1S,3aS,3bS,5aR,9aR,9bS,11aS)-6,9a,11a-trimethyl-1-(nonylamino)-2,3,3a,3b,4,5,5a,8,9,9b,10,11-dodecahydro-1H-indeno[5,4-f]quinolin-7-one
• CAS: 845914-03-6
• 化学式: C₂₈H₅₀N₂O
• 分子量: 430.718
• InChiKey: PXFLCWZYIMHLJO-LOVBUXKDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.2
• 重原子数：
  31
• 可旋转键数：
  9
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.96
• 拓扑面积：
  32.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  17-β-(N-nonylamino)-4-methyl-4-aza-5-α-androstan-3-one 在 N,O-双(三甲基硅烷基)三氟乙酰胺 、 臭氧 、 potassium hydroxide 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 甲醇 、 二氯甲烷 、 水 为溶剂， 反应 28.5h， 生成 17β-(N-t-butoxycarbonyl-N-nonylamino)-10α-hydroxymethyl-5β-N-methylamino-des-A-androstane
  参考文献：
  名称：

  靶向 17β-羟基类固醇脱氢酶 7 型抑制剂的合成和表征。

  摘要：

  雌激素雌二醇 (E2) 和雄激素二氢睾酮 (DHT) 等性类固醇激素与激素依赖性癌症的发生有关。阻断 7 型 17β-羟基类固醇脱氢酶 (17β-HSD7)（短链脱氢酶/还原酶超家族的成员）被认为会降低 E2 水平，同时增加 DHT 水平。因此，其独特的双重作用使该酶成为治疗乳腺癌的有趣药物靶点。描述了新型氨基甲酸酯衍生物 3 和 4 的化学合成、分子表征和作为 17β-HSD7 抑制剂的初步生物学评价。与之前的 17β-HSD7 抑制剂 1 和 2 一样，化合物 3 和 4 在 4-aza-5α-雄甾烷核的 C-17β 位置带有疏水性壬基侧链，但化合物 3 的氧原子取代了类固醇中的 CH2 A环C-2位置，而化合物4具有含有氨基甲酸酯官能团的C17-螺环E环。它们均抑制 17β-HSD7 在体外将雌酮 (E1) 转化为 E2，但引入 (17R)-螺氨基甲酸酯优于用氧原子取代 C-2 亚甲基，因为化合物

  DOI：

  10.1016/j.jsbmb.2024.106544
• 作为产物：
  描述：

  在 sodium tetrahydroborate 作用下， 以 甲醇 为溶剂， 反应 1.5h， 以530 mg的产率得到17-β-(N-nonylamino)-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.
• 10.1016/j.jsbmb.2024.106544
  作者：Sancéau, Jean-Yves、Maltais, René、Zhou, Ming、Lin, Sheng-Xiang、Poirier, Donald

  DOI：10.1016/j.jsbmb.2024.106544

  日期：——

  double action makes this enzyme as an interesting drug target for treatment of breast cancer. The chemical synthesis, molecular characterization, and preliminary biological evaluation as 17β-HSD7 inhibitors of novel carbamate derivatives 3 and 4 are described. Like previous 17β-HSD7 inhibitors 1 and 2, compounds 3 and 4 bear a hydrophobic nonyl side chain at the C-17β position of a 4-aza-5α-androstane

  雌激素雌二醇 (E2) 和雄激素二氢睾酮 (DHT) 等性类固醇激素与激素依赖性癌症的发生有关。阻断 7 型 17β-羟基类固醇脱氢酶 (17β-HSD7)（短链脱氢酶/还原酶超家族的成员）被认为会降低 E2 水平，同时增加 DHT 水平。因此，其独特的双重作用使该酶成为治疗乳腺癌的有趣药物靶点。描述了新型氨基甲酸酯衍生物 3 和 4 的化学合成、分子表征和作为 17β-HSD7 抑制剂的初步生物学评价。与之前的 17β-HSD7 抑制剂 1 和 2 一样，化合物 3 和 4 在 4-aza-5α-雄甾烷核的 C-17β 位置带有疏水性壬基侧链，但化合物 3 的氧原子取代了类固醇中的 CH2 A环C-2位置，而化合物4具有含有氨基甲酸酯官能团的C17-螺环E环。它们均抑制 17β-HSD7 在体外将雌酮 (E1) 转化为 E2，但引入 (17R)-螺氨基甲酸酯优于用氧原子取代 C-2 亚甲基，因为化合物