3β-hydroxypregn-4,16-diene-6,20-dione | 851591-91-8

• 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-hydroxypregn-4,16-diene-6,20-dione
• 英文别名: 3beta-Hydroxypregna-4,16-diene-6,20-dione；(3S,8R,9S,10R,13S,14S)-17-acetyl-3-hydroxy-10,13-dimethyl-1,2,3,7,8,9,11,12,14,15-decahydrocyclopenta[a]phenanthren-6-one
• CAS: 851591-91-8
• 化学式: C₂₁H₂₈O₃
• 分子量: 328.452
• InChiKey: NRKNAJASAODYII-QLDKISDLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  24
• 可旋转键数：
  1
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.71
• 拓扑面积：
  54.4
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3β-hydroxypregn-4,16-diene-6,20-dione 在 chromium(VI) oxide 作用下， 以 水 、 丙酮 为溶剂， 以80%的产率得到pregna-4,16-diene-3,6,20-trione
  参考文献：
  名称：

  New 5?-reductase inhibitors: In vitro and in vivo effects

  摘要：

  The enzyme 5 alpha-reductase is responsible for the conversion of testosterone (T) to its more potent androgen dihydrotestosterone (DHT). This steroid had been implicated in androgen-dependent diseases such as: benign prostatic hyperplasia. prostate cancer, acne and androgenic alopecia. The inhibition of 5 alpha-reductase enzyme offers a potentially useful treatment for these diseases.In this study, we report the synthesis and pharmacological evaluation of several new 3-substituted pregna-4, 16-diene-6, 20-dione derivatives. These compounds were prepared from the commercially available 16-dehydropregnenolone acetate. The biological activity of the new steroidal derivatives was determined in vivo as well as in vitro experiments.In vivo experiments, the anti-androgenic effect of the steroids was demonstrated by the decrease of the weight of the prostate gland of gonadectomized hamster treated with T plus finasteride or the new steroids. The IC50 value of these steroids was determined by measuring the conversion of radio labeled T to DHT.The results of this study carried out with 5 alpha-reductase enzyme from hamster and human prostate showed that four of the six steroidal derivatives (5, 7, 9, 10) exhibited much higher 5 alpha-reductase inhibitory activity, as indicated by the IC50 values than the presently used Proscar 3 (finasteride).The comparison of the weight of the hamster's prostate gland indicated that compound 5 had a comparable weight decrease as finasteride. The overall data of this study showed very clearly those compounds 5, 7, 9, 10 are good inhibitors for the 5 alpha-reductase enzyme. (c) 2005 Elsevier Inc. All rights reserved.

  DOI：

  10.1016/j.steroids.2004.11.008
• 作为产物：
  描述：

  3β-acetoxy-5,6-epoxy-16-pregnen-20-one 在 吡啶 、 chromium(VI) oxide 、 氯化亚砜 、 水 、 sodium hydroxide 作用下， 以 甲醇 、 二氯甲烷 、 水 、 丙酮 为溶剂， 反应 1.75h， 生成 3β-hydroxypregn-4,16-diene-6,20-dione
  参考文献：
  名称：

  3β-肉桂酰氧基取代的 pregna-4,16-diene-6,20-diones 衍生物的合成、计算机和体内抗炎评价

  摘要：

  摘要 主要研究孕烷衍生物的 5α-还原酶活性。然而，此类化合物的抗炎活性仍未得到充分探索。在寻找新的抗炎药的过程中，制备了七种新的孕烷衍生物6a - g，在 C-3 位带有肉桂酸酯，并对其进行了全面表征。在 TPA 诱导的小鼠耳模型中评估化合物的抗炎活性。其中，化合物6b对减轻水肿最有效，ED 50为 0.017 毫克/耳。此外，还进行了分子对接和分子动力学研究，以确定与炎症过程相关的潜在分子靶点。体内结果表明6 b可能是一种有效的抗炎化合物，而计算机研究表明它与炎症反应中的一些关键酶相互作用。

  DOI：

  10.1080/07391102.2021.1969279

文献信息

• Synthesis and cytotoxic effect of pregnenolone derivatives with one or two α,β-unsaturated carbonyls and an ester moiety at C-21 or C-3
  作者：Alejandra Chávez-Riveros、Abigail Cruz Noriega、María Teresa Ramírez Apan、Luis D. Miranda、Eugene Bratoeff

  DOI：10.1016/j.steroids.2018.01.004

  日期：2018.3

  cell lines).Determination of the cytotoxic effect of the steroids with one or two &agr;,&bgr;‐unsaturated carbonyls.The steroids with 4‐fluorinated benzoic acid ester at C‐21 were cytotoxic against SKLU‐1 cell line. ABSTRACT Four series of pregnenolone derivatives having one or two &agr;,&bgr;‐unsaturated carbonyls and an ester moiety at C‐21 or C‐3 were synthetized to compare their cytotoxicity effect

  图形抽象图。没有可用的字幕。亮点合成四个系列的孕烯醇酮衍生物。C-21 或 C-3 上具有酯基的类固醇的细胞毒性比较研究（在四种细胞系中）。具有一种或两种 &agr;,&bgr 的类固醇的细胞毒性作用的测定;-不饱和羰基。在 C-21 处具有 4-氟化苯甲酸酯的类固醇对 SKLU-1 细胞系具有细胞毒性。摘要合成了四个系列的孕烯醇酮衍生物，它们具有一个或两个 &agr;,&bgr;-不饱和羰基和一个 C-21 或 C-3 的酯部分，以比较它们的细胞毒性作用。在三种人类癌细胞系上评估了最终化合物：PC-3（前列腺癌）、MCF-7（乳腺癌）、SKLU-1（肺癌）和非癌细胞系 HGF（人牙龈成纤维细胞）。
• Biological activity of novel progesterone derivatives having a bulky ester side chains at C-3
  作者：Marisa Cabeza、Eugene Bratoeff、Elena Ramírez、Ivonne Heuze、Sergio Recillas、Hilda Berrios、Angel Cruz、Olmo Cabrera、Victor Perez

  DOI：10.1016/j.steroids.2008.03.006

  日期：2008.9

  castrated hamsters treated with dihydrotestosterone. The four compounds bind to the androgen receptor with different relative binding affinity (RBA). Compound 9d having a logP of 4.17 showed the highest RBA>100% as compared to compound 9a having a logP of 2.92 which exhibited a RBA of only 2.85%. These data show a very good correlation between the lipophilicity of these compounds represented by logP and

  抗雄激素作为雄激素受体 (AR) 作用的抑制剂被广泛用于治疗雄激素依赖性疾病。虽然抗雄激素作用的确切机制尚未阐明，但最近的研究表明配体的结构与核共阻遏物有关。在本研究中，我们研究了四种孕烷衍生物 9a-9d 的 logP（分配系数）与其生物活性之间的关系。为此，我们使用标记的米勃龙 (MIB) 作为配体，测定了类固醇 9a-9d 与从大鼠前列腺细胞质中获得的雄激素受体 (AR) 的相对结合亲和力 (RBA)。根据浓度与结合百分比的关系图计算每种化合物的 IC(50) 值。9a-9d 的体内作用是根据用二氢睾酮处理的去势仓鼠的前列腺和精囊的重量确定的。这四种化合物以不同的相对结合亲和力 (RBA) 与雄激素受体结合。与具有仅2.85%的RBA的具有2.92的logP的化合物9a相比，具有4.17的logP的化合物9d显示出最高的RBA>100%。这些数据显示由 logP 表示的这些化合物的亲脂性与
• Synthesis and cytotoxic effect on cancer cell lines and macrophages of novel progesterone derivatives having an ester or a carbamate function at C-3 and C-17
  作者：Alejandra Chávez-Riveros、Mariana Garrido、María Teresa Ramírez Apan、Armando Zambrano、Mario Díaz、Eugene Bratoeff

  DOI：10.1016/j.ejmech.2014.06.008

  日期：2014.7

  In this study we report the cytotoxic effect on human cancer cells of two series of novel progesterone derivatives; the first containing an aromatic ester (8a-e) or a carbamate functions both linked to C-3 (9a -e) on the pregn-4,16-diene-6,20-dione skeleton. In the second series, both functional groups (ester and carbamate) are bound to C-17 on the pregn-4,6-diene-3,20-dione scaffold (13a-e and 14a-e). The panel cancer cell lines used in this study were the following: PC-3 (human prostate cancer cell line), MCF-7 (human breast cancer cell line), HCT-15 (human colon cancer cell line) and J774 (noncancerous murine macrophages) for comparison.The results from this study showed that steroid 14a, having a carbamate function at C-17, was the most potent against PC-3 cell line (96.6%) while 8c and 8e showed much higher cytotoxic activity (100%) for MCF-7 cell line. Finally, compounds 8c and 14a displayed selective properties towards tumor cell lines than noncancerous murine macrophages. (C) 2014 Elsevier Masson SAS. All rights reserved.
• Effect of new hybrids based on 5,16-pregnadiene scaffold linked to an anti-inflammatory drug on the growth of a human astrocytoma cell line (U373)
  作者：Mariana Garrido、Aliesha González-Arenas、Ignacio Camacho-Arroyo、Marisa Cabeza、Belén Alcaraz、Eugene Bratoeff

  DOI：10.1016/j.ejmech.2015.01.048

  日期：2015.3

  In spite of the fact that anaplastic astrocytoma is an uncommon disease, very often the pathology of this disease is associated with lethal effects due to the late diagnosis and unspecific treatments. This paper reports the synthesis and the biological effect on the growth of U373 cell line (human anaplastic astrocytoma) of new hybrid compounds based on 5,16-pregnadiene scaffold linked to an anti-inflammatory drug (6a-e). Moreover, we also determined the cell growth effect of five non-steroidal anti-inflammatory drugs (naproxen, ibuprofen, ketoprofen, indomethacin and sulindac) as well as the free steroidal alcohol 5. The results from this study indicated that sulindac as well as compound 5 decreased the number of U373 cells at different concentrations. However, when an anti-inflammatory drug was bound to the steroidal structure (5), the resulting compounds (6a-e) showed an enhanced biological effect with exception of hybrid 6c. Furthermore, derivative 6e (sulindac hybrid) did not allow cell growth during six days of experiment at a concentration of 10 mu M. The overall data indicated that these molecules showed an anti-proliferative activity on anaplastic astrocytoma cell line. (C) 2015 Elsevier Masson SAS. All rights reserved.
• Synthesis, <i>in silico</i>, and <i>in vivo</i> anti-inflammatory evaluation of 3β-cinnamoyloxy substituted pregna-4,16-diene-6,20-diones derivatives
  作者：Elkin Sanabria-Chanaga、Dulce María Meneses-Ruiz、Erick Francisco Puertas-Santamaría、Fernando Manuel Mancha-Meléndez、Eugene Bratoeff、Marco A. Loza-Mejía、Juan Rodrigo Salazar

  DOI：10.1080/07391102.2021.1969279

  日期：2022.12.12

  Abstract Pregnane derivatives have been studied mainly for their 5α-reductase activity. However, the anti-inflammatory activities of such compounds are still poorly explored. In the search for new anti-inflammatory agents, seven new pregnane derivatives 6a-g, with cinnamic acid esters at C-3 were prepared and fully characterized. The anti-inflammatory activity of compounds was assessed in TPA induced

  摘要 主要研究孕烷衍生物的 5α-还原酶活性。然而，此类化合物的抗炎活性仍未得到充分探索。在寻找新的抗炎药的过程中，制备了七种新的孕烷衍生物6a - g，在 C-3 位带有肉桂酸酯，并对其进行了全面表征。在 TPA 诱导的小鼠耳模型中评估化合物的抗炎活性。其中，化合物6b对减轻水肿最有效，ED 50为 0.017 毫克/耳。此外，还进行了分子对接和分子动力学研究，以确定与炎症过程相关的潜在分子靶点。体内结果表明6 b可能是一种有效的抗炎化合物，而计算机研究表明它与炎症反应中的一些关键酶相互作用。