androst-5-ene-7,17,19-trione | 2751-67-9

• 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: androst-5-ene-7,17,19-trione
• 英文别名: (8R,9S,10S,13S,14S)-13-methyl-7,17-dioxo-2,3,4,8,9,11,12,14,15,16-decahydro-1H-cyclopenta[a]phenanthrene-10-carbaldehyde
• CAS: 2751-67-9
• 化学式: C₁₉H₂₄O₃
• 分子量: 300.398
• InChiKey: LHDMACWWIQYSTK-BHHKEHIISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  22
• 可旋转键数：
  1
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.74
• 拓扑面积：
  51.2
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  androst-5-ene-7,17,19-trione 在 氢氧化钾 作用下， 以 甲醇 、 水 为溶剂， 反应 2.75h， 以21%的产率得到estr-5-ene-7,17-dione
  参考文献：
  名称：

  Synthesis of Androst-5-en-7-ones and Androsta-3,5-dien-7-ones and Their Related 7-Deoxy Analogs as Conformational and Catalytic Probes for the Active Site of Aromatase

  摘要：

  A series of androst-5-en-7-ones and androsta-3,5-dien-7-ones and their 7-deoxy derivatives, respectively, were synthesized and tested for their abilities to inhibit aromatase in human placental microsomes. All the steroids inhibited the enzyme in a competitive manner with K-i's ranging from 0.058 to 45 mu M. The inhibitory activities of 17-oxo compounds were much more potent than those of the corresponding 17 beta-alcohols in each series. Steroids having an oxygen function (hydroxy or carbonyl) at C-19 were less potent inhibitors than the corresponding parent compounds having a 19-methyl group. 3,5-Dien-7-one 24 and its 19-hydroxy and 19-oxo derivatives (12 and 13) as well as 19-oxo-5-en-7-one 3 caused a time-dependent inactivation of aromatase only in the presence of NADPH in which the k(inact) values of 19-als 3 and 13 (0.143 and 0.189 min(-1), respectively) were larger than those of the corresponding 19-methyl (23 and 24) and 19-hydroxy (1 and 12) steroids, respectively. 19-Nor-5-en-7-one 4 but not its 3,5-diene derivative 14 also inactivated the enzyme in a time-dependent manner. In contrast, 7-deoxy steroids 21 and 27, having a 19-methyl group, did not cause it. The inactivations were prevented by the substrate androstenedione, and no significant effects of L-cysteine on the inactivations were observed in each case. The results suggest that oxygenation at C-19 would be at least in part involved in the inactivations caused by the inhibitors 23 and 24. The conjugated enone structures should play a critical role in the inactivation sequences.

  DOI：

  10.1021/jm00040a012
• 作为产物：
  描述：

  3β,19-Diacetoxy-17β-benzoyloxy-androst-5-en 在 chromium(VI) oxide 、 aluminum oxide 、 sodium chromate(VI) 、 硫酸 、 sodium acetate 、 乙酸酐 、 溶剂黄146 作用下， 以 丙酮 、 苯 为溶剂， 生成 androst-5-ene-7,17,19-trione
  参考文献：
  名称：

  Lederer,F.; Ourisson,G., Bulletin de la Societe Chimique de France, 1965, p. 1298 - 1308

  摘要：

  DOI：

文献信息

• Studies directed toward a mechanistic evaluation of aromatase inhibition by androst-5-ene-7,17-dione
  作者：Mitsuteru Numazawa、Mii Tachibana

  DOI：10.1016/s0039-128x(97)00002-0

  日期：1997.7

  To gain further insight into the mechanism for inactivation of aromatase by androst-5-ene-7,17-dione (1) and its 19-nor analog 4, 10 beta-oxygenated steroids 5 and 6, Delta(1(10))-steroid 7, and 19-oxo-5 beta,6 beta-epoxy compound 8 were synthesized and tested for their ability to inhibit aromatase in human placental microsomes. all of the steroids studied inhibited the enzyme in a competitive manner with apparent K-i values ranging from 1.1 to 35 mu M. The Delta(1(10))-compound 7 was the most potent inhibitor among them. All of the inhibitors caused a time-dependent inactivation of aromatase in the presence of NADPH in air with the K-inact values ranging from 0.036 to 0.190 min(-1). The substrate and androstenedione protected the inactivation, but a nucleophile, L-cystein, did not, in each case. In contrast, each inhibitor did not cause the time-dependent inactivation in the absence of NADPH. These results show that the 5 beta,6 beta-epoxide 8 and/or the dienone 7 are not a reactive electrophile involved in the irreversible binding to the active site of aromatase during the mechanism-based inactivation caused by the suicide substrates 1 and/or 4. (C) 1997 by Elsevier Science Inc.
• Lederer,F.; Ourisson,G., Bulletin de la Societe Chimique de France, 1965, p. 1298 - 1308
  作者：Lederer,F.、Ourisson,G.

  DOI：——

  日期：——
• Synthesis of Androst-5-en-7-ones and Androsta-3,5-dien-7-ones and Their Related 7-Deoxy Analogs as Conformational and Catalytic Probes for the Active Site of Aromatase
  作者：Mitsuteru Numazawa、Ayako Mutsumi、Mii Tachibana、Kumiko Hoshi

  DOI：10.1021/jm00040a012

  日期：1994.7

  A series of androst-5-en-7-ones and androsta-3,5-dien-7-ones and their 7-deoxy derivatives, respectively, were synthesized and tested for their abilities to inhibit aromatase in human placental microsomes. All the steroids inhibited the enzyme in a competitive manner with K-i's ranging from 0.058 to 45 mu M. The inhibitory activities of 17-oxo compounds were much more potent than those of the corresponding 17 beta-alcohols in each series. Steroids having an oxygen function (hydroxy or carbonyl) at C-19 were less potent inhibitors than the corresponding parent compounds having a 19-methyl group. 3,5-Dien-7-one 24 and its 19-hydroxy and 19-oxo derivatives (12 and 13) as well as 19-oxo-5-en-7-one 3 caused a time-dependent inactivation of aromatase only in the presence of NADPH in which the k(inact) values of 19-als 3 and 13 (0.143 and 0.189 min(-1), respectively) were larger than those of the corresponding 19-methyl (23 and 24) and 19-hydroxy (1 and 12) steroids, respectively. 19-Nor-5-en-7-one 4 but not its 3,5-diene derivative 14 also inactivated the enzyme in a time-dependent manner. In contrast, 7-deoxy steroids 21 and 27, having a 19-methyl group, did not cause it. The inactivations were prevented by the substrate androstenedione, and no significant effects of L-cysteine on the inactivations were observed in each case. The results suggest that oxygenation at C-19 would be at least in part involved in the inactivations caused by the inhibitors 23 and 24. The conjugated enone structures should play a critical role in the inactivation sequences.