3β-cyclopentylcarbonyloxy-5-androsten-17-one | 1345406-90-7

• 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: 3β-cyclopentylcarbonyloxy-5-androsten-17-one
• 英文别名: 17-oxaandrost-5-ene-3β-yl cyclopentanoate
• CAS: 1345406-90-7
• 化学式: C₂₅H₃₆O₃
• 分子量: 384.559
• InChiKey: XENLWDSXJTYBCK-FYVXYBBASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.62
• 重原子数：
  28.0
• 可旋转键数：
  2.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.84
• 拓扑面积：
  43.37
• 氢给体数：
  0.0
• 氢受体数：
  3.0

反应信息

• 作为反应物：
  描述：

  3β-cyclopentylcarbonyloxy-5-androsten-17-one 在 caesium carbonate 、 三氯氧磷 作用下， 以 氯仿 、 N,N-二甲基甲酰胺 为溶剂， 反应 8.5h， 生成 16-formyl-17-(1H-pyrazole-1-yl)androsta-5,16-dien-3β-yl cyclopentanoate
  参考文献：
  名称：

  Biological activity of pyrazole and imidazole-dehydroepiandrosterone derivatives on the activity of 17β-hydroxysteroid dehydrogenase

  摘要：

  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.

  DOI：

  10.3109/14756366.2014.1003926
• 作为产物：
  描述：

  环戊酸 、 去氢表雄酮 在 4-二甲氨基吡啶 、 N,N'-二环己基碳二亚胺 作用下， 以 二氯甲烷 为溶剂， 反应 2.0h， 以86.4%的产率得到3β-cyclopentylcarbonyloxy-5-androsten-17-one
  参考文献：
  名称：

  Crystal Structure and Synthesis of Three New Steroidal Derivatives as Antiandrogens

  摘要：

  通过光谱和 X 射线衍射研究，确定了化合物 1-3β-环丁基碳酰氧基-5-雄烯-17-酮（C24H34O3）、化合物 2-3β-环戊基碳酰氧基-5-雄烯-17-酮（C25H36O3）和化合物 3-3β-环己基碳酰氧基-5-雄烯-17-酮（C26H38O3）的结构。类固醇衍生物 1-3 具有很强的抗雄激素作用，可作为治疗前列腺癌的潜在药物。化合物 1 结晶于正交空间群 P212121，单胞参数 a = 6.618(2), β = 14.167(3), c = 22.化合物 2 在正交空间群 P212121 中结晶，其单胞参数为 a = 6.631(2)，b = 13.865(4)，c = 23.化合物 3 在正交空间群 P212121 中结晶，单胞参数 a = 6.6100(9), b = 13.这三种结构（1-3）均采用直接法求解，并分别精制为 R = 0.0708、0.0750 和 0.0496。化合物 2 的 C3 侧链存在位置紊乱。两个类固醇骨架的所有环均为反式连接。对于结构 1-3，六元环 A、B 和 C 具有变形椅状、半椅状和变形椅状构象。五元环 D 采用中间包络和半椅构象。在结构 2 中，五元环 E 和 EA 分别具有变形包络、中间包络和半椅构象。对于结构 3，六元环 E 采用变形椅构象。晶体的内聚力可归因于范德华和微弱的 C-H⋯O 相互作用。通过 X 射线衍射技术从合适的单晶体中获得了作为抗雄激素的三种新甾体衍生物的晶体结构及其构象。甾体衍生物 1-3 具有很强的抗雄激素作用，可作为治疗前列腺癌的潜在药物。

  DOI：

  10.1007/s10870-010-9806-7

文献信息

• 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.
• 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.