norhyodeoxycholic acid | 77518-23-1

• 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
• 英文名称: norhyodeoxycholic acid
• 英文别名: 3α,6α-dihydroxy-24-nor-5β-cholan-24-oic acid；24-norhyodeoxycholic acid；3α,6α-dihydroxy-24-nor-5β-cholan-23-oic acid；3α,6α-dihydroxy-24-nor-5β-cholanoic acid-(23)；3α,6α-Dihydroxy-24-nor-5β-cholansaeure-(23)；(3R)-3-[(3R,5R,6S,8S,9S,10R,13R,14S,17R)-3,6-dihydroxy-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-17-yl]butanoic acid
• CAS: 77518-23-1
• 化学式: C₂₃H₃₈O₄
• 分子量: 378.552
• InChiKey: ZBAVIUQLFUYWMT-NNUWNQTCSA-N

物化性质

• 熔点：
  197-198 °C(Solv: ethyl acetate (141-78-6); hexane (110-54-3))
• 沸点：
  536.7±25.0 °C(Predicted)
• 密度：
  1.142±0.06 g/cm3(Predicted)
• 溶解度：
  DMF：30mg/mL； DMF:PBS (pH 7.2) (1:1)：0.5mg/mL；二甲基亚砜：20mg/mL；乙醇：20mg/mL

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  27
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.96
• 拓扑面积：
  77.8
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  norhyodeoxycholic acid 在 乙醚 、 硫酸 、 乙酸酐 作用下， 生成 3α,6α-diacetoxy-23,23-diphenyl-24-nor-5β-cholene-(22)
  参考文献：
  名称：

  猪去氧胆酸的降解。

  摘要：

  DOI：

  10.1021/ja01213a052
• 作为产物：
  描述：

  猪去氧胆酸 在 高氯酸 、 三氟乙酸 、 三氟乙酸酐 、 potassium hydroxide 、 sodium nitrite 作用下， 以 乙醇 、 水 为溶剂， 反应 52.33h， 生成 norhyodeoxycholic acid
  参考文献：
  名称：

  海洋孕烷 X 受体激动剂 Solomonsterol B 的首次全合成

  摘要：

  已从市售猪脱氧胆酸开始开发了一种获得孕烷 X 受体 (PXR) 激动剂 solomonsterol B（一种从海洋海绵 Theonella swinhoei 中分离的天然产物）的简明途径。该合成的特点是单碳侧链降解和 A 环和 B 环的再官能化，以安装所需的反式连接和 C2 和 C3 上的两个羟基，形成反式关系。该方案取得了良好的产率（13 个步骤中的 10%），还允许制备侧链修饰的衍生物，可用于 PXR 的初步构效关系。solomonsterol B 的药理学特性表明，该化合物在反式激活试验中是 PXR 激动剂，当它与肝细胞一起孵育时，它增加了 PXR 调节基因的表达。

  DOI：

  10.1002/ejoc.201200619

文献信息

• Synthesis and Quantitative Structure-Property Relationships of Side Chain-Modified Hyodeoxycholic Acid Derivatives
  作者：Paola Sabbatini、Paolo Filipponi、Roccaldo Sardella、Benedetto Natalini、Roberto Nuti、Antonio Macchiarulo、Roberto Pellicciari、Antimo Gioiello

  DOI：10.3390/molecules180910497

  日期：——

  Bile acids have emerged as versatile signalling compounds of a complex network of nuclear and membrane receptors regulating various endocrine and paracrine functions. The elucidation of the interconnection between the biological pathways under the bile acid control and manifestations of hepatic and metabolic diseases have extended the scope of this class of steroids for in vivo investigations. In this framework, the design and synthesis of novel biliary derivatives able to modulate a specific receptor requires a deep understanding of both structure-activity and structure-property relationships of bile acids. In this paper, we report the preparation and the critical micellization concentration evaluation of a series of hyodeoxycholic acid derivatives characterized by a diverse side chain length and by the presence of a methyl group at the alpha position with respect to the terminal carboxylic acid moiety. The data collected are instrumental to extend on a quantitative basis, the knowledge of the current structure-property relationships of bile acids and will be fruitful, in combination with models of receptor activity, to design and prioritize the synthesis of novel pharmacokinetically suitable ligands useful in the validation of bile acid-responsive receptors as therapeutic targets.

  胆汁酸已成为一种多功能信号化合物，参与复杂的核内和膜受体网络，调节多种内分泌和旁分泌功能。阐明胆汁酸控制下的生物通路与肝脏及代谢疾病表现之间的相互联系，拓宽了这一类类固醇在体内研究中的应用范围。在此框架下，设计和合成能够调节特定受体的新型胆汁衍生物，需要深入理解胆汁酸的结构-活性关系和结构-性质关系。在本文中，我们报道了一系列氢脱氧胆酸衍生物的制备及其临界胶束化浓度的评估，这些衍生物的侧链长度多样，并在α位相对于末端羧酸基团的位置上具有一个甲基。收集的数据对于基于定量的扩展胆汁酸当前结构-性质关系的知识具有重要意义，并将与受体活性模型结合，为设计和优先合成在药物动力学上适用的新型配体提供有益支持，这些配体可用于验证胆汁酸响应受体作为治疗靶点的可行性。
• [EN] HYODEOXYCHOLIC ACID DERIVATIVES AND USE THEREOF<br/>[FR] DÉRIVÉS D'ACIDE HYODEOXYCHOLIQUE ET LEURS UTILISATIONS
  申请人：BAR PHARMACEUTICALS SOCIETA' A RESPONSABILITA' LIMITATA

  公开号：WO2018002897A1

  公开（公告）日：2018-01-04

  The present invention concerns compounds having formula (I) and compositions thereof with a pharmacologically acceptable excipient and uses thereof as a medicament, in particular for the treatment and/or prevention of a disorder selected from the group consisting of: gastrointestinal disorders, liver diseases, cardiovascular and vascular diseases, pulmonary and metabolic diseases, infectious diseases, cancer, renal disorders, inflammatory disorders comprising immune mediated disorders, and neurological disorders.

  本发明涉及具有式（I）的化合物及其与药用可接受的赋形剂的组合物，以及其作为药物的用途，特别是用于治疗和/或预防来自以下组中选择的紊乱：胃肠道疾病、肝脏疾病、心血管和血管疾病、肺部和代谢性疾病、传染病、癌症、肾脏疾病、包括免疫介导紊乱的炎症性疾病以及神经疾病。
• [EN] COMPOUND HAVING ANTISPORULANT ACTIVITY AND PHARMACEUTICAL COMPOSITION THEREOF<br/>[FR] COMPOSÉ PRÉSENTANT UNE ACTIVITÉ D'ANTISPORULANT ET COMPOSITION PHARMACEUTIQUE DE CELUI-CI<br/>[ZH] 一种具有抗芽孢活性的化合物及其药用组合物
  申请人：CHENGDU BIOBEL COMPANY LTD

  公开号：WO2021147123A1

  公开（公告）日：2021-07-29

  本发明提供了一种具有抗芽孢活性的化合物及其药用组合物，具体提供了式（I）所示的化合物、或其盐、或其立体异构体。该化合物能够有效抑制艰难梭菌芽孢的萌发，具有显著的抑菌活性，在制备预防和/或治疗艰难梭菌感染性疾病、艰难梭菌感染性疾病的复发、或艰难梭菌感染性疾病并发症的药物中具有非常好的应用前景。
• Chemical synthesis of 3β-sulfooxy-7β-hydroxy-24-nor-5-cholenoic acid: An internal standard for mass spectrometric analysis of the abnormal Δ5-bile acids occurring in Niemann-Pick disease
  作者：Genta Kakiyama、Akina Muto、Miki Shimada、Nariyasu Mano、Junichi Goto、Alan F. Hofmann、Takashi Iida

  DOI：10.1016/j.steroids.2009.04.007

  日期：2009.9

  In Niemann-Pick disease, type C1, increased amounts of 3 beta,7 beta-dihydroxy-5-cholenoic acid are reported to be present in urinary bile acids. The compound occurs as a tri-conjugate, sulfated at C-3, N-acetylglucosamidated at C-7, and N-acylamidated with taurine or glycine at C-24. For sensitive LC-MS/MS analysis of this bile acid, a suitable internal standard is needed. We report here the synthesis of a satisfactory internal standard, 3 beta-sulfooxy-7 beta-hydroxy-24-nor-5-cholenoic acid (as the disodium salt). The key reactions involved were (1) the so-called "second order" Beckmann rearrangement (one-carbon degradation at C-24) of hyodeoxycholic acid (HDCA) 3,6-diformate with sodium nitrite in a mixture of trifluoroacetic anhydride and trifluoroacetic acid, (2) simultaneous inversion at C-3 and elimination at C-6 of the ditosylate derivatives of the resulting 3 alpha,6 alpha-dihydroxy-24-nor-5 beta-cholanoic acid with potassium acetate in aqueous N,N-dimethylformamide, and (3) regioselective sulfation at C-3 of an intermediary 3 beta,7 beta-dihydroxy-24-nor-Delta(5) derivative using sulfur trioxide-trimethylamine complex. Overall yield of the desired compound was 1.8% in 12 steps from HDCA. (C) 2009 Elsevier Inc. All rights reserved.
• Synthesis of sulfonate analogs of bile acids
  作者：Kihira Kenji、Mikami Takahiro、Ikawa Seiichiro、Okamoto Akira、Yoshii Michiko、Miki Shigeo、Erwin H. Mosbach、Hoshita Takahiko

  DOI：10.1016/0039-128x(92)90008-w

  日期：1992.4

  Sulfonate analogs of C23 and C24 bile acids were synthesized from norcholic, norchenodeoxycholic, norursodeoxycholic, nordeoxycholic, norhyodeoxycholic, cholic, deoxycholic, hyodeoxycholic, and lithocholic acids. The principal reactions used were (1) reduction of the bile acids with NaBH4 to the corresponding bile alcohols, (2) selective tosylation of the terminal hydroxyl group, (3) iodination of the tosyl esters with NaI, and (4) treatment of the iodides with Na2SO3 to form the sulfonate analogs of the bile acids. The sulfonate analogs showed polarity similar to that of taurine-conjugated bile acids on thin-layer chromatography. The carbon 13 nuclear magnetic resonance spectral data for the sulfonate analogs were tabulated.