Hexanoic acid (6S,8R,9S,10R,13S,14S)-10,13-dimethyl-3,17-dioxo-2,3,6,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-6-yl ester

• 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: Hexanoic acid (6S,8R,9S,10R,13S,14S)-10,13-dimethyl-3,17-dioxo-2,3,6,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-6-yl ester
• 英文别名: [(6S,8R,9S,10R,13S,14S)-10,13-dimethyl-3,17-dioxo-2,6,7,8,9,11,12,14,15,16-decahydro-1H-cyclopenta[a]phenanthren-6-yl] hexanoate
• 化学式: C₂₅H₃₆O₄
• 分子量: 400.558
• InChiKey: AMIDPDOKRBRJTC-TTZDETBQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  29
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.8
• 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：

  Hexanoic acid (6S,8R,9S,10R,13S,14S)-10,13-dimethyl-3,17-dioxo-2,3,6,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-6-yl ester 在 2,3-二氯-5,6-二氰基-1,4-苯醌 作用下， 以 苯 为溶剂， 反应 10.0h， 以45%的产率得到Hexanoic acid (6S,8R,9S,10R,13S,14S)-10,13-dimethyl-3,17-dioxo-6,7,8,9,10,11,12,13,14,15,16,17-dodecahydro-3H-cyclopenta[a]phenanthren-6-yl ester
  参考文献：
  名称：

  Probing the binding pocket of the active site of aromatase with 6-ether or 6-ester substituted androst-4-ene-3,17-diones and their diene and triene analogs

  摘要：

  A series of 6-ester- (3 and 4) and 6-ether- (7 and 8) substituted androst-4-ene-3,17-diones (androstenediones) and their 1,4-diene analogs (5 and 6, and 9 and 10) as well as CB-substituted 4,6-diene and 1,4,6-triene steroids 11 and 12 were synthesized as aromatase inhibitors to gain insight into the structure-activity relationship between various substituents and inhibitory activity. All of the inhibitors synthesized blocked aromatase in a competitive manner. The inhibitory activities of all of the steroids, except for the 6 beta -benzoates 4g and 6h and the 6 beta -acetate 6a, were fairly effective to very powerful (K-i: 7.0 -320 nM). The 6 alpha -n-hexanoyloxy- and 6 alpha -benzyloxyandrostenediones (3e and 7e) were the most potent inhibitors (K-i: 7.0 nM each). In the series of 4-ene and 1,4-diene steroids, the 6 alpha -substituted steroids had higher affinity for the enzyme than the corresponding 6 beta -isomers. In the 1,4-diene steroid series, 6 beta -substituted steroids 6a, e, g, and 10a, b, e caused a time-dependent inactivation of aromatase, whereas their 6 alpha -isomers 5 and 9 essentially did not. The ether-substituted 1,4,6-trienes 12 inactivated the enzyme in a time-dependent manner; in contrast, their 4,6-diene analogs 11 did not. The substrate androstenedione blocked the inactivation, but no significant effect of L-cysteine was observed. Based on molecular modeling with the PM3 method, along with the present inhibition and inactivation results, it is thought that both the steric effects of the 6-substituents as well as the electronic effects of the C-6 oxygen functions play a critical role in the binding of inhibitors to the active site of aromatase. (C) 2000 Elsevier Science Inc. All rights reserved.

  DOI：

  10.1016/s0039-128x(00)00169-0
• 作为产物：
  描述：

  己酸酐 、 6α-hydroxy-androst-4-ene-3,17-dione 在 吡啶 作用下， 反应 6.0h， 以75%的产率得到Hexanoic acid (6S,8R,9S,10R,13S,14S)-10,13-dimethyl-3,17-dioxo-2,3,6,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-6-yl ester
  参考文献：
  名称：

  Probing the binding pocket of the active site of aromatase with 6-ether or 6-ester substituted androst-4-ene-3,17-diones and their diene and triene analogs

  摘要：

  A series of 6-ester- (3 and 4) and 6-ether- (7 and 8) substituted androst-4-ene-3,17-diones (androstenediones) and their 1,4-diene analogs (5 and 6, and 9 and 10) as well as CB-substituted 4,6-diene and 1,4,6-triene steroids 11 and 12 were synthesized as aromatase inhibitors to gain insight into the structure-activity relationship between various substituents and inhibitory activity. All of the inhibitors synthesized blocked aromatase in a competitive manner. The inhibitory activities of all of the steroids, except for the 6 beta -benzoates 4g and 6h and the 6 beta -acetate 6a, were fairly effective to very powerful (K-i: 7.0 -320 nM). The 6 alpha -n-hexanoyloxy- and 6 alpha -benzyloxyandrostenediones (3e and 7e) were the most potent inhibitors (K-i: 7.0 nM each). In the series of 4-ene and 1,4-diene steroids, the 6 alpha -substituted steroids had higher affinity for the enzyme than the corresponding 6 beta -isomers. In the 1,4-diene steroid series, 6 beta -substituted steroids 6a, e, g, and 10a, b, e caused a time-dependent inactivation of aromatase, whereas their 6 alpha -isomers 5 and 9 essentially did not. The ether-substituted 1,4,6-trienes 12 inactivated the enzyme in a time-dependent manner; in contrast, their 4,6-diene analogs 11 did not. The substrate androstenedione blocked the inactivation, but no significant effect of L-cysteine was observed. Based on molecular modeling with the PM3 method, along with the present inhibition and inactivation results, it is thought that both the steric effects of the 6-substituents as well as the electronic effects of the C-6 oxygen functions play a critical role in the binding of inhibitors to the active site of aromatase. (C) 2000 Elsevier Science Inc. All rights reserved.

  DOI：

  10.1016/s0039-128x(00)00169-0

文献信息

• Probing the binding pocket of the active site of aromatase with 6-ether or 6-ester substituted androst-4-ene-3,17-diones and their diene and triene analogs
  作者：Mitsuteru Numazawa、Momoko Shelangouski、Mina Nagasaka

  DOI：10.1016/s0039-128x(00)00169-0

  日期：2000.12

  A series of 6-ester- (3 and 4) and 6-ether- (7 and 8) substituted androst-4-ene-3,17-diones (androstenediones) and their 1,4-diene analogs (5 and 6, and 9 and 10) as well as CB-substituted 4,6-diene and 1,4,6-triene steroids 11 and 12 were synthesized as aromatase inhibitors to gain insight into the structure-activity relationship between various substituents and inhibitory activity. All of the inhibitors synthesized blocked aromatase in a competitive manner. The inhibitory activities of all of the steroids, except for the 6 beta -benzoates 4g and 6h and the 6 beta -acetate 6a, were fairly effective to very powerful (K-i: 7.0 -320 nM). The 6 alpha -n-hexanoyloxy- and 6 alpha -benzyloxyandrostenediones (3e and 7e) were the most potent inhibitors (K-i: 7.0 nM each). In the series of 4-ene and 1,4-diene steroids, the 6 alpha -substituted steroids had higher affinity for the enzyme than the corresponding 6 beta -isomers. In the 1,4-diene steroid series, 6 beta -substituted steroids 6a, e, g, and 10a, b, e caused a time-dependent inactivation of aromatase, whereas their 6 alpha -isomers 5 and 9 essentially did not. The ether-substituted 1,4,6-trienes 12 inactivated the enzyme in a time-dependent manner; in contrast, their 4,6-diene analogs 11 did not. The substrate androstenedione blocked the inactivation, but no significant effect of L-cysteine was observed. Based on molecular modeling with the PM3 method, along with the present inhibition and inactivation results, it is thought that both the steric effects of the 6-substituents as well as the electronic effects of the C-6 oxygen functions play a critical role in the binding of inhibitors to the active site of aromatase. (C) 2000 Elsevier Science Inc. All rights reserved.