17α-acetoxy-16β-methylpregna-4,6-diene-3,20-dione | 220280-51-3

• 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: 17α-acetoxy-16β-methylpregna-4,6-diene-3,20-dione
• 英文别名: [(8R,9S,10R,13S,14S,16S,17R)-17-acetyl-10,13,16-trimethyl-3-oxo-2,8,9,11,12,14,15,16-octahydro-1H-cyclopenta[a]phenanthren-17-yl] acetate
• CAS: 220280-51-3
• 化学式: C₂₄H₃₂O₄
• 分子量: 384.516
• InChiKey: BEBORRDOQIGVSP-GMLTVKBZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  28
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.71
• 拓扑面积：
  60.4
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  17α-acetoxy-16β-methylpregna-4,6-diene-3,20-dione 在 间氯过氧苯甲酸 作用下， 反应 3.0h， 生成 Acetic acid (6R,7S,8R,9S,10R,13S,14S,16S,17R)-17-acetyl-10,13,16-trimethyl-3-oxo-2,3,6,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-20-oxa-cyclopropa[6,7]cyclopenta[a]phenanthren-17-yl ester
  参考文献：
  名称：

  Androgenic and anti-androgenic effects of progesterone derivatives with different halogens as substituents at the C-6 position

  摘要：

  The pharmacological activities of four pregnane derivatives: 17 alpha-hydroxy-16 beta-methylpregna-4,6-diene-3,20-dione (7), 17 alpha-acetoxy-16 beta-methylpregna-4,6-diene-3,20-dione (8), 17 alpha-acetoxy-6-bromo-16 beta-methylpregna-4,6-diene-3,20-dione (10), and 17 alpha-acetoxy-6-chloro-16 beta-methylpregna-4,6-diene-3,20-dione (11), were determined. The derivatives were evaluated on gonadectomized male hamster flank organs and seminal vesicles. The results indicate that topical applications of testosterone (T) on the flank organs increased the diameter of the pigmented spot. Similarly, the same phenomenon occurred on the glands treated with compound 11, whereas compound 10 decreased the size of the spot significantly. In this study, we determined the effects of several new steroids on the conversion of T to DHT in flank organs and seminal vesicles. The results show that compound 10 inhibited T conversion to DHT, but compound 11, at a dose of 200 mu g, stimulated T conversion in both flank organs and seminal vesicles. However, when 2 mg of compound 11 was applied, it inhibited the conversion of T to DHT, suggesting that this compound also represses gonadotropin release. The difference between compounds 10 and II involves the electronegativity of the halogen at the C-6 position of the progesterone skeleton. These data clearly indicate that by decreasing the electronegativity of the halogen at C-6 (compound 10), 5 alpha-reductase is inhibited in both tissues and at different pHs. On the other hand, when the electronegativity of the halogen atom was increased (11), there was a much lower inhibitory effect on the conversion of T to DHT. (C) 1999 Elsevier Science Inc. All rights reserved.

  DOI：

  10.1016/s0039-128x(99)00018-5
• 作为产物：
  描述：

  16-脱氢孕烯醇酮乙酸酯 在 吡啶 、 copper(l) iodide 、 hydroxide 、 双氧水 、 溴 、 lithium carbonate 、 对甲苯磺酸 、 溶剂黄146 、 三氟乙酸酐 、 lithium bromide 、 原甲酸三甲酯 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 N,N-二甲基甲酰胺 、 丙酮 为溶剂， 反应 109.0h， 生成 17α-acetoxy-16β-methylpregna-4,6-diene-3,20-dione
  参考文献：
  名称：

  Androgenic and anti-androgenic effects of progesterone derivatives with different halogens as substituents at the C-6 position

  摘要：

  The pharmacological activities of four pregnane derivatives: 17 alpha-hydroxy-16 beta-methylpregna-4,6-diene-3,20-dione (7), 17 alpha-acetoxy-16 beta-methylpregna-4,6-diene-3,20-dione (8), 17 alpha-acetoxy-6-bromo-16 beta-methylpregna-4,6-diene-3,20-dione (10), and 17 alpha-acetoxy-6-chloro-16 beta-methylpregna-4,6-diene-3,20-dione (11), were determined. The derivatives were evaluated on gonadectomized male hamster flank organs and seminal vesicles. The results indicate that topical applications of testosterone (T) on the flank organs increased the diameter of the pigmented spot. Similarly, the same phenomenon occurred on the glands treated with compound 11, whereas compound 10 decreased the size of the spot significantly. In this study, we determined the effects of several new steroids on the conversion of T to DHT in flank organs and seminal vesicles. The results show that compound 10 inhibited T conversion to DHT, but compound 11, at a dose of 200 mu g, stimulated T conversion in both flank organs and seminal vesicles. However, when 2 mg of compound 11 was applied, it inhibited the conversion of T to DHT, suggesting that this compound also represses gonadotropin release. The difference between compounds 10 and II involves the electronegativity of the halogen at the C-6 position of the progesterone skeleton. These data clearly indicate that by decreasing the electronegativity of the halogen at C-6 (compound 10), 5 alpha-reductase is inhibited in both tissues and at different pHs. On the other hand, when the electronegativity of the halogen atom was increased (11), there was a much lower inhibitory effect on the conversion of T to DHT. (C) 1999 Elsevier Science Inc. All rights reserved.

  DOI：

  10.1016/s0039-128x(99)00018-5

文献信息

• Synthesis and Pharmacological Evaluation of New Progesterone Esters as 5.ALPHA.-Reductase Inhibitors
  作者：Elena Ramírez、Marisa Cabeza、Eugene Bratoeff、Ivonne Heuze、Víctor Pérez、David Valdez、Martha Ochoa、Nayeli Teran、Geidy Jimenez、Teresa Ramírez

  DOI：10.1248/cpb.53.1515

  日期：——

  In this study we report the synthesis and pharmacological evaluation of four new progesterone derivatives; 17α-hydroxy-16β-methylpregna-4,6-diene-3,20-dione 12, 17α-cyclopropylcarbonyloxy-16β-methylpregna-4,6-diene-3,20-dione 13, 17α-cyclobutylcarbonyloxy-16β-methylpregna-4,6-diene-3,20-dione 14, 17α-acetoxy-16β-methylpregna-4,6-diene-3,20-dione 15 and the pregnatriene compound 17α-cyclobutylcarbonyloxy-16β-methylpregna-1,4,6-triene-3,20-dione 16. The pharmacological effect of these compounds was determined in vivo as well as in vitro. The evaluation in vivo was carried out on gonadectomized male hamsters that were injected subcutaneously daily with testosterone (T) and/or finasteride, or with the novel compounds. At the end of the treatments the animals were sacrificed and the prostates were weighed. It was observed that when testosterone (T) and finasteride or compounds 12—16 were injected together, the weight of the prostate decreased significantly as compared to that of the testosterone-treated animals. The 5α-reductase inhibitory activity was evaluated in vitro using human prostate homogenates. These experiments showed the following IC50 values: compound 12 (alcohol at C-17) 1.2×10−6 M, 13 (cyclopropyl substituent at C-17) 7.9×10−10 M, 14 (cyclobutyl substituent) 3.2×10−8 M, 15 (acetoxy substituent) 6.3×10−11 M and 16 (cyclobutyl substituent) 3.9×10−6 M. It is evident from these data that when the size of the substituent at C-17 is decreased, the 5α-reductase inhibitory activity increases. Apparently, in this biological model, the 5α-reductase inhibitory activity depends upon the steric effect of the substituent at C-17. However, the free alcohol 12 showed much lower 5α-reductase inhibitory activity.

  在这项研究中，我们报告了四种新黄体酮衍生物的合成和药理学评价； 17α-羟基-16β-甲基孕酮-4,6-二烯-3,20-二酮 12, 17α-环丙基羰氧基-16β-甲基孕酮-4,6-二烯-3,20-二酮 13, 17α-环丁基羰氧基-16β-甲基孕酮- 4,6-二烯-3,20-二酮 14, 17α-乙酰氧基-16β-甲基孕酮-4,6-二烯-3,20-二酮15及孕三烯化合物17α-环丁基羰氧基-16β-甲基孕酮-1,4,6-三烯-3,20-二酮16药理作用在体内和体外测定了这些化合物的含量。体内评估是在去性腺切除的雄性仓鼠上进行的，这些仓鼠每天皮下注射睾酮（T）和/或非那雄胺，或新化合物。治疗结束时处死动物并称重前列腺。据观察，当睾酮（T）和非那雄胺或化合物12-16一起注射时，与睾酮治疗的动物相比，前列腺的重量显着下降。使用人前列腺匀浆在体外评估 5α-还原酶抑制活性。这些实验显示了以下 IC50 值：化合物 12（C-17 处的醇）1.2×10−6 M, 13（C-17 处的环丙基取代基）7.9×10−10 M< /small>, 14 (环丁基取代基) 3.2×10−8 M, 15 (乙酰氧基取代基) 6.3×10−11 M 和 16（环丁基取代基）3.9×10−6 M。从这些数据可以明显看出，当C-17处的取代基的大小减小时，5α-还原酶抑制活性增加。显然，在该生物模型中，5α-还原酶抑制活性取决于C-17取代基的空间效应。然而，游离醇12表现出低得多的5α-还原酶抑制活性。
• Androgenic and anti-androgenic effects of progesterone derivatives with different halogens as substituents at the C-6 position
  作者：M Cabeza、E Gutiérrez、R Miranda、I Heuze、E Bratoeff、G Flores、E Ramı́rez

  DOI：10.1016/s0039-128x(99)00018-5

  日期：1999.6

  The pharmacological activities of four pregnane derivatives: 17 alpha-hydroxy-16 beta-methylpregna-4,6-diene-3,20-dione (7), 17 alpha-acetoxy-16 beta-methylpregna-4,6-diene-3,20-dione (8), 17 alpha-acetoxy-6-bromo-16 beta-methylpregna-4,6-diene-3,20-dione (10), and 17 alpha-acetoxy-6-chloro-16 beta-methylpregna-4,6-diene-3,20-dione (11), were determined. The derivatives were evaluated on gonadectomized male hamster flank organs and seminal vesicles. The results indicate that topical applications of testosterone (T) on the flank organs increased the diameter of the pigmented spot. Similarly, the same phenomenon occurred on the glands treated with compound 11, whereas compound 10 decreased the size of the spot significantly. In this study, we determined the effects of several new steroids on the conversion of T to DHT in flank organs and seminal vesicles. The results show that compound 10 inhibited T conversion to DHT, but compound 11, at a dose of 200 mu g, stimulated T conversion in both flank organs and seminal vesicles. However, when 2 mg of compound 11 was applied, it inhibited the conversion of T to DHT, suggesting that this compound also represses gonadotropin release. The difference between compounds 10 and II involves the electronegativity of the halogen at the C-6 position of the progesterone skeleton. These data clearly indicate that by decreasing the electronegativity of the halogen at C-6 (compound 10), 5 alpha-reductase is inhibited in both tissues and at different pHs. On the other hand, when the electronegativity of the halogen atom was increased (11), there was a much lower inhibitory effect on the conversion of T to DHT. (C) 1999 Elsevier Science Inc. All rights reserved.