17-oxaandrost-5-ene-3β-yl p-chlorobenzoate | 913722-75-5

• 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: 17-oxaandrost-5-ene-3β-yl p-chlorobenzoate
• 英文别名: 17-Oxo-5-androsten-3beta-yl 4-chlorobenzoate；[(3S,8R,9S,10R,13S,14S)-10,13-dimethyl-17-oxo-1,2,3,4,7,8,9,11,12,14,15,16-dodecahydrocyclopenta[a]phenanthren-3-yl] 4-chlorobenzoate
• CAS: 913722-75-5
• 化学式: C₂₆H₃₁ClO₃
• 分子量: 426.983
• InChiKey: NODJIUHYSGXDLK-BNCSLUSBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.1
• 重原子数：
  30
• 可旋转键数：
  3
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.62
• 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：

  17-oxaandrost-5-ene-3β-yl p-chlorobenzoate 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 7.0h， 生成 16-formyl-17-(1H-pyrazole-1-yl)androsta-5,16-diene-3β-yl p-chlorobenzoate
  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 吡啶 、 potassium hydroxide 作用下， 以 甲醇 为溶剂， 反应 12.0h， 生成 17-oxaandrost-5-ene-3β-yl p-chlorobenzoate
  参考文献：
  名称：

  Synthesis, antiproliferative activity, acute toxicity and assessment of the antiandrogenic activities of new androstane derivatives

  摘要：

  以市售的(25R)-5-螺烯-3β-醇（薯蓣皂苷）（4）为起始原料，合成了一些 17-氧代-5-雄烯-3β-基酯（9a-9f）和 3β-烷氧基-5-雄烯-17-酮（11a-11e）。评估了合成化合物对前列腺癌细胞株 DU-145 的抗增殖活性、急性毒性和对血清雄激素水平的影响，并与作为阳性对照的非那雄胺进行了比较。其中一些化合物的细胞毒性和抗雄激素活性优于阳性对照。报告了合成化合物的详细合成、光谱数据和生物活性。

  DOI：

  10.1007/s12272-011-0702-2

文献信息

• Activity of steroid 4 and derivatives 4a–4f as inhibitors of the enzyme 5α-reductase 1
  作者：Yazmín Arellano、Eugene Bratoeff、Yvonne Heuze、Marisol Bravo、Juan Soriano、Marisa Cabeza

  DOI：10.1016/j.bmc.2018.06.030

  日期：2018.8

  produced in that organ. These cells exhibit grater type 1 5α-reductase (5α-R1) activity than type 2 5α-reductase. Noteworthy, both isozymes convert testosterone (T) to the more active androgen dihydrotestosterone (DHT) in the target tissues. Thus, in order to potentially improve the prognosis of this disease, in this work, seven derivatives of 17-(1H-benzimidazol-1-yl)-16-formillandrosta-5,16-dien-3β-yl

  已知前列腺转移性骨肿瘤的生长取决于雄激素，并且肿瘤形成可以从该器官中产生的迁移性恶性细胞开始。这些细胞比2型5α还原酶具有1型5α还原酶（5α-R1）活性。值得注意的是，两种同工酶都在靶组织中将睾丸激素（T）转化为活性更高的雄激素二氢睾丸激素（DHT）。 因此，为了潜在地改善该疾病的预后，在这项工作中，使用了17-（1 H-苯并咪唑-1-基）-16-甲腈-5,16-二烯-3β-苯甲酸酯的7种衍生物（4a–合成了f）和17-（1 H-苯并咪唑-1-基）-3-羟基-16-甲酰二茂基-5,16-二烯（4），并将其鉴定为1型5α-还原酶（5αR1）的抑制剂。这些衍生物具有改善的血浆半衰期的优点。 向5α-R1同工酶的化合物的抑制活性是通过转化的T到DHT中的存在或不存在化合物的确定4，图4a-f的。此外，在体内实验也在进行，治疗与T和/或去势仓鼠4，图4a-f的和仓鼠的直径评价其效果侧翼器官和在前
• <i>In vivo</i>and<i>in vitro</i>effect of androstene derivatives as 5α-reductase type 1 enzyme inhibitors
  作者：Eugene Bratoeff、Araceli Sánchez、Yazmín Arellano、Yvonne Heuze、Juan Soriano、Marisa Cabeza

  DOI：10.3109/14756366.2012.729827

  日期：2013.12.1

  prostate cytosol. Steroids 1-12 containing different substituents in the phenyl group of the ester moiety in C-3 reduced the flank organs and inhibited the activity of 5α-R type 1; however only steroids 1 and 2 inhibited 5α-R type 2. 1-12 did not bind to the AR. The modification of one atom of the substituents in the phenyl group of the ester moiety in C-3 changed their biological potency (IC50).

  这些研究的目的是合成具有治疗潜力的十二种脱氢表雄酮的酯衍生物。在用睾丸激素和合成的类固醇治疗的性腺切除的仓鼠的胁腹器官中证明了1-12的作用。进行了体外研究，确定了抑制1α和2型5α-还原酶活性的IC50值，它们分别存在于大鼠肝脏和人前列腺中。使用大鼠的前列腺细胞溶质确定1-12与雄激素受体（AR）的结合。在C-3的酯部分的苯基中含有不同取代基的类固醇1-12减少了侧翼器官并抑制了5α-R1型的活性。然而，仅类固醇1和2抑制2型5α-R。1-12不与AR结合。
• 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.
• 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.
• Synthesis, antiproliferative activity, acute toxicity and assessment of the antiandrogenic activities of new androstane derivatives
  作者：Neelima Dhingra、T. R. Bhardwaj、Neeraj Mehta、Tapas Mukhopadhyay、Ashok Kumar、Manoj Kumar

  DOI：10.1007/s12272-011-0702-2

  日期：2011.7

  A number of 17-oxo-5-androsten-3β-yl esters (9a–9f) and 3β-alkoxy-5-androsten-17-ones (11a–11e) were synthesized from commercially available (25R)-5-spirosten-3β-ol (Diosgenin) (4) as starting material. The synthesized compounds were evaluated for their antiproliferative activity against the prostate-specific cancer cell line DU-145, acute toxicity and effect on serum androgen levels, and compared with finasteride as positive control. Some of the compounds exhibited better cytotoxicity and antiandrogenic activity than the reference control. The detailed synthesis, spectroscopic data and biological activity of the synthesized compounds are reported.

  以市售的(25R)-5-螺烯-3β-醇（薯蓣皂苷）（4）为起始原料，合成了一些 17-氧代-5-雄烯-3β-基酯（9a-9f）和 3β-烷氧基-5-雄烯-17-酮（11a-11e）。评估了合成化合物对前列腺癌细胞株 DU-145 的抗增殖活性、急性毒性和对血清雄激素水平的影响，并与作为阳性对照的非那雄胺进行了比较。其中一些化合物的细胞毒性和抗雄激素活性优于阳性对照。报告了合成化合物的详细合成、光谱数据和生物活性。