(4R)-4-[(8R,9S,10R,12S,13R,14S,17R)-12-羟基-10,13-二甲基-3-氧代-1,2,8,9,11,12,14,15,16,17-十氢环戊烯并[a]菲-17-基]戊酸 | 13535-96-1

• 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
• 中文名称: (4R)-4-[(8R,9S,10R,12S,13R,14S,17R)-12-羟基-10,13-二甲基-3-氧代-1,2,8,9,11,12,14,15,16,17-十氢环戊烯并[a]菲-17-基]戊酸
• 英文名称: 3-oxo-12α-hydroxy-4,6-choladien-24-oic acid
• 英文别名: 12α-hydroxy-3-oxochola-4,6-dien-24-oic acid；12α-hydroxy-3-oxo-5β-chola-4,6-dien-24-oic acid；12α-Hydroxy-3-oxo-chola-4,6-dien-24-saeure；12α-Hydroxy-3-oxo-choladien-(4,6)-saeure-(24)；12alpha-Hydroxy-3-oxochola-4,6-dien-24-oic Acid；(4R)-4-[(8R,9S,10R,12S,13R,14S,17R)-12-hydroxy-10,13-dimethyl-3-oxo-1,2,8,9,11,12,14,15,16,17-decahydrocyclopenta[a]phenanthren-17-yl]pentanoic acid
• CAS: 13535-96-1
• 化学式: C₂₄H₃₄O₄
• 分子量: 386.532
• InChiKey: DJVAMCYXFUWMLS-QUPGBHKMSA-N

物化性质

• 熔点：
  252-254 °C(Solv: ethanol (64-17-5))
• 沸点：
  580.4±50.0 °C(Predicted)
• 密度：
  1.18±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  28
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.75
• 拓扑面积：
  74.6
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (4R)-4-[(8R,9S,10R,12S,13R,14S,17R)-12-羟基-10,13-二甲基-3-氧代-1,2,8,9,11,12,14,15,16,17-十氢环戊烯并[a]菲-17-基]戊酸 在 chromium(VI) oxide 作用下， 生成 3,12-dioxo-chola-4,6-dien-24-oic acid methyl ester
  参考文献：
  名称：

  Adenocarcinoma of the nonpigmented ciliary epithelium: report of two cases with immunohistochemical findings

  摘要：

  Background: Acquired neoplasms arising from the nonpigmented ciliary epithelium (NPCE) are much less common than uveal melanocytic proliferations. We report two cases of acquired neoplasms arising from the NPCE with immunohistochemical findings. Methods: Case reports. Results and conclusions: Patient 1 was a 39-year-old man who presented with a pigmented mass behind the iris and secondary exudative retinal detachment. The eye also developed neovascular glaucoma. Patient 2 was a 44-year-old woman with a ciliary body mass but without symptoms. Both of these tumors were classified histologically as low-grade adenocarcinomas of the NPCE from specimens successfully removed by iridocyclectomy. Immunohistochemical findings confirmed the origin of the tumor cells. however. some changes in the immunoreactivity to cytokeratin AE1 and epithelial membrane antigen were found.

  DOI：

  10.1007/s004170100353
• 作为产物：
  描述：

  7-酮基-3alpha,12alpha-二羟基胆烷酸 在 aspergillus cinnamomeus 、 cultures of aspergillus cinnamomeus 作用下， 生成 (4R)-4-[(8R,9S,10R,12S,13R,14S,17R)-12-羟基-10,13-二甲基-3-氧代-1,2,8,9,11,12,14,15,16,17-十氢环戊烯并[a]菲-17-基]戊酸
  参考文献：
  名称：

  Hasegawa, Hiroshima Journal of Medical Sciences, 1959, vol. 8, p. 271,272

  摘要：

  DOI：

文献信息

• Screening the binding affinity of bile acid derivatives for the glucocorticoid receptor ligand-binding domain
  作者：Srdjan Bjedov、Sofija Bekic、Maja Marinovic、Dusan Skoric、Ksenija Pavlovic、Andjelka Celic、Edward Petri、Marija Sakac

  DOI：10.2298/jsc220912078b

  日期：——

  The necessity of anti-inflammatory drugs such as glucocorticoids has been evident during the COVID-19 pandemic. Glucocorticoids, are the standard therapy for the treatment of moderate and severe COVID-19 patients. However, serious side effects limit the use of these drugs, and anti-inflammatory drugs with better pharmacological properties are urgently required. Bile acids are of interest, because of their anti-inflammatory and immunomodulatory properties, facilitated through an unclear mechanism involving transmembrane and nuclear receptors. In this work, we screened the binding activity of a number of bile acid derivatives, for the ligand-binding domain of glucocorticoid receptor (GR-LBD), the most important receptor for anti-inflammatory processes. Tested compounds include oximes, lactones, lactams, tetrazoles, dienones, C-24 alcohols and cholic acid amides. Cholic acid oxime, deoxycholic acid dienone, 3-keto-24-cholic alcohol and cholic acid amide showed best binding affinities for GR-LBD among tested compounds. The in silico molecular docking explanation is provided. SAR analysis showed that expansion of B and C steroid rings or attachment of heterocycle to C ring is not beneficial for binding; side chain should contain hydrogen donor group; the GR-LBD tolerate well different functionalities on C-3 position. These results provide valuable information toward synthesis of the new glucocorticoids based on bile acids.

  在 COVID-19 大流行期间，糖皮质激素等抗炎药物的必要性显而易见。糖皮质激素是治疗中度和重度 COVID-19 患者的标准疗法。然而，严重的副作用限制了这些药物的使用，因此迫切需要药理特性更好的抗炎药物。胆汁酸具有抗炎和免疫调节特性，其机制尚不明确，涉及跨膜受体和核受体，因此备受关注。在这项工作中，我们筛选了一些胆汁酸衍生物与糖皮质激素受体（GR-LBD）配体结合域的结合活性，糖皮质激素受体是抗炎过程中最重要的受体。受测化合物包括肟类、内酯类、内酰胺类、四唑类、二烯酮类、C-24 醇类和胆酸酰胺类。在测试的化合物中，胆酸肟、脱氧胆酸二烯酮、3-酮基-24-胆酸醇和胆酸酰胺与 GR-LBD 的结合亲和力最佳。本研究提供了硅学分子对接解释。SAR 分析表明，类固醇 B 环和 C 环的扩展或杂环与 C 环的连接不利于结合；侧链应包含氢供体基团；GR-LBD 能很好地耐受 C-3 位置上的不同官能团。这些结果为基于胆汁酸合成新的糖皮质激素提供了有价值的信息。
• Improved synthesis of 3-keto, 4-ene-3-keto, and 4,6-diene-3-keto bile acids
  作者：Raymond A. Leppik

  DOI：10.1016/0039-128x(83)90087-9

  日期：1983.4

  Cholic and deoxycholic acids can be converted into 3-keto derivatives in 75-80% yield, by a four-step synthesis consisting of formylation, selective deformylation of the 3-formoxyl group, oxidation, then deformylation of the remaining formoxyl groups. The intermediate 3-keto formoxyl acids in this sequence were shown to be suitable starting compounds for the synthesis of 4-ene-3-keto acids, in 55-60% yield, via bromination, dehydrobromination, and deformylation. By extending the dehydrobromination reaction, the 7 alpha-formoxyl group of the intermediate 4-ene-3-keto-7 alpha,12 alpha-diformoxyl acid is also lost, hence providing a useful synthetic route to 4,6-diene-3-keto bile acids.
• Matsumoto, Journal of Biochemistry, 1944, vol. 36, p. 183,189
  作者：Matsumoto

  DOI：——

  日期：——
• MICROBIOLOGICAL DEGRADATION OF BILE ACIDS
  作者：SHOHEI HAYAKAWA、YASUO SABURI、HIDEYUKI HOSHIJIMA

  DOI：10.1093/oxfordjournals.jbchem.a126889

  日期：1958.7
• Tamaki, Journal of Biochemistry, 1958, vol. 45, p. 299,301
  作者：Tamaki

  DOI：——

  日期：——