16-formyl-17-chloroandrost-5,16-diene-3β-yl cyclopropanoate | 1470067-57-2

• 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: 16-formyl-17-chloroandrost-5,16-diene-3β-yl cyclopropanoate
• 英文别名: 16-formyl-17-chloroandrosta-5,16-diene-3β-ylcyclopropanecarboxylate；17-chloro-16-formyl-androsta-5,16-dien-3β-yl cyclopropanoate；[(3S,8R,9S,10R,13S,14S)-17-chloro-16-formyl-10,13-dimethyl-2,3,4,7,8,9,11,12,14,15-decahydro-1H-cyclopenta[a]phenanthren-3-yl] cyclopropanecarboxylate
• CAS: 1470067-57-2
• 化学式: C₂₄H₃₁ClO₃
• 分子量: 402.961
• InChiKey: KMCUFWGSXBXDEX-MMJASOHGSA-N

物化性质

• 沸点：
  500.7±50.0 °C(Predicted)
• 密度：
  1.22±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  28
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.75
• 拓扑面积：
  43.4
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1H-1,2,4-三唑 、 16-formyl-17-chloroandrost-5,16-diene-3β-yl cyclopropanoate 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 3.0h， 以93%的产率得到16-formyl-17-(1H-1,2,4-triazole-1-yl)androsta-5,16-diene-3β-yl cyclopropanoate
  参考文献：
  名称：

  Cytotoxic effect of novel dehydroepiandrosterone derivatives on different cancer cell lines

  摘要：

  The aim of this study was to determine the cytotoxic effect of human cancer cells on three series of novel dehydroepiandrosterone derivatives containing triazole or pyrazole rings at C-17 and an ester moiety at C-3 of the androstane skeleton. The panel cancer cells used in this study were the following: PC-3, MCF-7 and SKLU-1.The results from this study indicated that the steroidal derivatives 4a-4e and 4f-4k showed the highest cytotoxic potency. This difference in this activity could be attributed to the ability of the triazole (three nitrogen atoms) to form stronger hydrogen bonds with the active site of the cell as compared to the pyrazole group having two nitrogen atoms.Compounds 4f-4k having an aromatic ester at C-3 showed an enhanced cytotoxic activity as compared to their aliphatic counterparts 4a-4e. Apparently the electronegative phenyl ring increased the polarity of the molecule, thus increasing the dipole dipole association of the steroidal molecule with the reactive site of the cell. (C) 2013 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2013.02.031
• 作为产物：
  描述：

  醋酸去氢表雄酮 在 4-二甲氨基吡啶 、 N,N'-二环己基碳二亚胺 、 sodium hydroxide 、 三氯氧磷 作用下， 以 甲醇 、 氯仿 为溶剂， 反应 5.0h， 生成 16-formyl-17-chloroandrost-5,16-diene-3β-yl cyclopropanoate
  参考文献：
  名称：

  新型脱氢表雄酮苯并咪唑基衍生物作为5α-还原酶同工酶抑制剂。

  摘要：

  5α-R同工酶（1型和2型）在前列腺发育中起重要作用，因为当生理性血清睾丸激素（T）浓度低时，它们负责前列腺内二氢睾丸激素（DHT）的水平。在这项研究中，我们合成了7个在C-17上具有苯并咪唑部分的新型脱氢表雄酮衍生物，并确定了它们对1α和2型5α-还原酶活性的影响。抑制5α-R1活性，而那些在C-3上带有脂环族酯（环丙基，环丁基或环戊基环）或醇基的化合物抑制两种同工酶的活性。在C-3处具有环己基或环庚基酯的衍生物没有抑制活性。在药理实验中 具有C 3-3的具有醇或脂族基团的酯或三个较小的脂环族环之一的酯的衍生物降低了雄性仓鼠胁腹器官的直径，其中环丁酯和环戊基酯显示出更高的作用。除环丁酯和环戊酯外，这些化合物可减轻前列腺和精囊的重量。

  DOI：

  10.3109/14756366.2015.1070843

文献信息

• Effect of dehydroepiandrosterone derivatives on the activity of 5α-reductase isoenzymes and on cancer cell line PC-3
  作者：Eugene Bratoeff、Mariana Garrido、Teresa Ramírez-Apan、Yvonne Heuze、Araceli Sánchez、Juan Soriano、Marisa Cabeza

  DOI：10.1016/j.bmc.2014.08.019

  日期：2014.11

  It is well known that testosterone (T) under the influence of 5 alpha-reductase enzyme is converted to dihydrotestosterone (DHT), which causes androgen-dependent diseases. The aim of this study was to synthesize new dehydroepiandrosterone derivatives (3a-e, 4a-i, 6 and 7) having potential inhibitory activity against the 5 alpha-reductase enzyme. This paper also reports the in vivo pharmacological effect of these steroidal molecules. The results from this study showed that all compounds exhibited low inhibitory activity for 5 alpha-reductase type 1 and 2 enzymes and they failed to bind to the androgen receptor. Furthermore, in the in vivo experiment, steroids 3b, 4f, and 4g showed comparable antiandrogenic activity to that of finasteride; only derivatives 4d and 7 produced a considerable decrease in the weight of the prostate gland of gonadectomized hamsters treated with (T). On the other hand, compounds 4a, f and h showed 100% inhibition of the growth of prostate cancer cell line PC-3, with compound 4g having a 98.2% antiproliferative effect at 50 mu M. The overall data indicated that these steroidal molecules, having an aromatic ester moiety at C-3 (4f-h), could have anticancer properties. (C) 2014 Elsevier Ltd. All rights reserved.
• Biological activity of pyrazole and imidazole-dehydroepiandrosterone derivatives on the activity of 17<b>β</b>-hydroxysteroid dehydrogenase
  作者：Marisa Cabeza、Alejandro Posada、Araceli Sánchez-Márquez、Yvonne Heuze、Isabel Moreno、Juan Soriano、Mariana Garrido、Francisco Cortés、Eugene Bratoeff

  DOI：10.3109/14756366.2014.1003926

  日期：2016.1.2

  The enzyme type 5 17 beta-hydroxysteroid dehydrogenase 5 (17 beta-HSD5) catalyzes the transformation of androstenedione (4-dione) to testosterone (T) in the prostate. This metabolic pathway remains active in cancer patients receiving androgen deprivation therapy. Since physicians seek to develop advantageous and better new treatments to increase the average survival of these patients, we synthesized several different dehydroepiandrosterone derivatives. These compounds have a pyrazole or imidazole function at C-17 and an ester moiety at C-3 and were studied as inhibitors of 17 beta-HSD5. The kinetic parameters of this enzyme were determined for use in inhibition assays. Their pharmacological effect was also determined on gonadectomized hamsters treated with Delta(4)-androstenedione (4-dione) or testosterone (T) and/or the novel compounds. The results indicated that the incorporation of a heterocycle at C-17 induced strong 17 beta-HSD5 inhibition. These derivatives decreased flank organ diameter and prostate weight in castrated hamsters treated with T or 4-dione. Inhibition of 17 beta-HSD5 by these compounds could have therapeutic potential for the treatment of prostate cancer and benign prostatic hyperplasia.
• Cytotoxic effect of novel dehydroepiandrosterone derivatives on different cancer cell lines
  作者：Mariana Garrido、Marisa Cabeza、Francisco Cortés、José Gutiérrez、Eugene Bratoeff

  DOI：10.1016/j.ejmech.2013.02.031

  日期：2013.10

  The aim of this study was to determine the cytotoxic effect of human cancer cells on three series of novel dehydroepiandrosterone derivatives containing triazole or pyrazole rings at C-17 and an ester moiety at C-3 of the androstane skeleton. The panel cancer cells used in this study were the following: PC-3, MCF-7 and SKLU-1.The results from this study indicated that the steroidal derivatives 4a-4e and 4f-4k showed the highest cytotoxic potency. This difference in this activity could be attributed to the ability of the triazole (three nitrogen atoms) to form stronger hydrogen bonds with the active site of the cell as compared to the pyrazole group having two nitrogen atoms.Compounds 4f-4k having an aromatic ester at C-3 showed an enhanced cytotoxic activity as compared to their aliphatic counterparts 4a-4e. Apparently the electronegative phenyl ring increased the polarity of the molecule, thus increasing the dipole dipole association of the steroidal molecule with the reactive site of the cell. (C) 2013 Elsevier Masson SAS. All rights reserved.
• Novel dehydroepiandrosterone benzimidazolyl derivatives as 5<b>α</b>-reductase isozymes inhibitors
  作者：Yazmín Arellano、Eugene Bratoeff、Tania Segura、Maria Eugenia Mendoza、Araceli Sánchez-Márquez、Yesica Medina、Yvonne Heuze、Juan Soriano、Marisa Cabeza

  DOI：10.3109/14756366.2015.1070843

  日期：2016.11.1

  5α-reductase types 1 and 2. The derivatives with an aliphatic ester at C-3 of the dehydroepiandrosterone scaffold induced specific inhibition of 5α-R1 activity, whereas those with a cycloaliphatic ester (cyclopropyl, cyclobutyl, or cyclopentyl ring) or an alcohol group at C-3 inhibited the activity of both isozymes. Derivatives with a cyclohexyl or cycloheptyl ester at C-3 showed no inhibitory activity. In pharmacological

  5α-R同工酶（1型和2型）在前列腺发育中起重要作用，因为当生理性血清睾丸激素（T）浓度低时，它们负责前列腺内二氢睾丸激素（DHT）的水平。在这项研究中，我们合成了7个在C-17上具有苯并咪唑部分的新型脱氢表雄酮衍生物，并确定了它们对1α和2型5α-还原酶活性的影响。抑制5α-R1活性，而那些在C-3上带有脂环族酯（环丙基，环丁基或环戊基环）或醇基的化合物抑制两种同工酶的活性。在C-3处具有环己基或环庚基酯的衍生物没有抑制活性。在药理实验中 具有C 3-3的具有醇或脂族基团的酯或三个较小的脂环族环之一的酯的衍生物降低了雄性仓鼠胁腹器官的直径，其中环丁酯和环戊基酯显示出更高的作用。除环丁酯和环戊酯外，这些化合物可减轻前列腺和精囊的重量。