甘氨鹅脱氧胆酸-[D9] | 640-79-9

• 物质功能分类: 生物化工 - 生化试剂 - 激动剂抑制剂
• 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: 甘氨鹅脱氧胆酸-[D9]
• 中文别名: 甘氨鹅脱氧胆酸；甘氨鹅去氧胆酸
• 英文名称: glycochenodeoxycholate
• 英文别名: Glycylchenodeoxycholic acid；(3α,7α-dihydroxy-24-oxo-5β-cholan-24-oic acid N-(carboxymethyl)amide)；N-[(3α,5β,7α)-3,7-dihydroxy-24-oxocholan-24-yl]glycine；chenodeoxycholic acid glycine conjugate；chenodeoxycholic acid glycine-conjugate；glycochenodeoxycholic acid；2-[[(4R)-4-[(3R,5S,7R,8R,9S,10S,13R,14S,17R)-3,7-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]pentanoyl]amino]acetic acid
• CAS: 640-79-9
• 化学式: C₂₆H₄₃NO₅
• 分子量: 449.631
• InChiKey: GHCZAUBVMUEKKP-GYPHWSFCSA-N

物化性质

• 沸点：
  655.6±40.0 °C(Predicted)
• 密度：
  1.162±0.06 g/cm3(Predicted)
• 溶解度：
  二甲基亚砜：≥29mg/mL（64.50mM）
• 物理描述：
  Solid
• 碰撞截面：
  203.3 Ų [M+Na]+ [CCS Type: DT, Method: single field calibrated with Agilent tune mix (Agilent)]

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  32
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.92
• 拓扑面积：
  107
• 氢给体数：
  4
• 氢受体数：
  5

安全信息

• 储存条件：
  -20°C

制备方法与用途

生物活性 Glycochenodeoxycholic acid（甘氧胆酸，胆烷基甘氨酸，甘氨酸鹅去氧胆酸盐）是由肝脏中鹅去氧胆酸盐与甘氨酸结合形成的胆汁盐。它作为一种去垢剂，能够溶解脂肪，从而促进吸收。

靶点 Human Endogenous Metabolite（人类内源性代谢物）

反应信息

• 作为反应物：
  描述：

  甘氨鹅脱氧胆酸-[D9] 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 10.0h， 生成 9-(3-((((R)-4-((3R,5S,7R,8R,9S,10S,13R,14S,17R)-3,7-dihydroxy-10,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthren-17-yl)pentanoyl)glycyl)oxy)propoxy)-10-methoxy-5,6-dihydro-[1,3]dioxolo[4,5-g]isoquinolino[3,2-a]isoquinolin-7-ium chloride
  参考文献：
  名称：

  Synthesis, Anticancer Activities, Antimicrobial Activities and Bioavailability of Berberine-Bile Acid Analogues

  摘要：

  合成了十五种小檗碱–胆酸类似物。与小檗碱（BBR）相比，这些类似物的抗癌活性在体外进行了评估；在这些类似物中，A4、B4 和 B5 的细胞毒性高于 BBR。大多数类似物对金黄色葡萄球菌 ATCC 25923 和白色念珠菌 ATCC 8799 具有较高的抗菌活性，而对枯草芽孢杆菌 AS 1.398 和大肠杆菌 ATCC 31343 则无敏感性。A4 和 B4 在血清稳定性实验中表现出稳定性。B4 在小鼠中显示出良好的口服生物利用度。

  DOI：

  10.2174/157018012800673010
• 作为产物：
  描述：

  鹅去氧胆酸 在 1,4-二氧六环 、 三正丁胺 、 氯甲酸乙酯 作用下， 生成 甘氨鹅脱氧胆酸-[D9]
  参考文献：
  名称：

  Norman, Arkiv foer Kemi, 1956, vol. 8, p. 331,338

  摘要：

  DOI：

文献信息

• [EN] BILE ACID-GCPII INHIBITOR CONJUGATES TO TREAT INFLAMMATORY DISEASES<br/>[FR] CONJUGUÉS INHIBITEURS DE GCPII-ACIDE BILIAIRE POUR TRAITER DES MALADIES INFLAMMATOIRES
  申请人：UNIV JOHNS HOPKINS

  公开号：WO2021155167A1

  公开（公告）日：2021-08-05

  GCPII inhibitors comprising 2-(phosphonomethyl) pentanedioic acid (2-PMPA) conjugated to a bile acid and their use for treating a disease or condition associated with elevated levels of GCPII, including inflammatory bowel disease.

  GCPII抑制剂包括2-(磷酸甲基)戊二酸（2-PMPA）与胆酸结合，并且它们用于治疗与GCPII水平升高相关的疾病或症状，包括炎症性肠病。
• [EN] SOLUBLE COMPLEXES OF DRUG ANALOGS AND ALBUMIN<br/>[FR] COMPLEXES SOLUBLES D'ANALOGUES DE MÉDICAMENT ET D'ALBUMINE
  申请人：FL THERAPEUTICS LLC

  公开号：WO2014121033A1

  公开（公告）日：2014-08-07

  The present invention provides novel, non-covalently bound complexes of serum albumin and analogs of poorly soluble drugs, such as camptothecin. The novel complexes are significantly more water-soluble than the camptothecin analogs and are useful as prodrug forms of the camptothecin analogs for the treatment of mammalian cell proliferative diseases, such as cancer.

  本发明提供了血清白蛋白与溶解度较差药物的类似物（如喜树碱）的新型非共价结合复合物。这些新型复合物比喜树碱类似物更易溶于水，并可用作喜树碱类似物的前药形式，用于治疗哺乳动物细胞增殖性疾病，如癌症。
• [EN] ABIRATERONE DERIVATIVES AND NON-COVALENT COMPLEXES WITH ALBUMIN<br/>[FR] DÉRIVÉS D'ABIRATÉRONE ET COMPLEXES NON COVALENTS AVEC L'ALBUMINE
  申请人：FL THERAPEUTICS LLC

  公开号：WO2015200837A1

  公开（公告）日：2015-12-30

  The present disclosure provides derivatives of abiraterone, non-covalently bound complexes of the abiraterone derivatives with serum albumin, pharmaceutical compositions of the same, and methods of use thereof. The non-covalently bound complexes are significantly more water-soluble than abiraterone and are useful for the treatment of a disease or condition that can benefit from CYP17 inhibition, such as prostate cancer.

  本公开提供了阿比特龙的衍生物，阿比特龙衍生物与血清白蛋白的非共价结合复合物，以及这些药物组合物的制备方法和使用方法。这些非共价结合复合物比阿比特龙具有更高的水溶性，可用于治疗需要CYP17抑制的疾病或病况，如前列腺癌。
• 2,5- OR 2,6-DISUBSTITUTED HYDROQUINONE DERIVATIVES WITH AT LEAST ONE CARBOXY, SULFO OR AMIDO GROUP USEFUL AS MEDICAMENTS
  申请人：OM Pharma SA

  公开号：EP3878837A1

  公开（公告）日：2021-09-15

  The invention provides hydroquinone derivatives of formula (I), processes of preparation, as well as pharmaceutical compositions and methods of treating and/or preventing e.g. autoimmune, immunological, rheumatology, vascular, ophthalmologic, fibrotic, metabolic and gastro-intestinal disorders, neuroinflammatory and neurodegenerative diseases, neoplasms and cancer associated disorders, hormone related diseases and immunological disorders resulting from viral and bacterial infectious diseases and complications thereof. wherein: Ra, Rb = H, acyl or aryl alkyl; R1 = COOR4, (CH2)nCOOR4, SO3H, (CH2)nSO3H or CONH-R10; R2 and R3 = H or R5, with the proviso that when one of R2 and R3 is R5, the other is H; R4 = H, alkyl or aryl alkyl; R5 = R6, R7 or R8; R6 = CONH-R9, CONHCOR9, CONH(CH2)n- R9, CONHCH(COOR4)(CH2)k R9 or heteroaryl-R9; k = 0-4; R7 = optionally substituted benzoheteroaryl ; R8 = (CH 2)mX(CH2)p R9; X = O, S, SO2, NH, NAc or N(CH2)q R9; R9 = optionally substituted aryl, heteroaryl or cycloalkyl ; R10 = optionally substituted aryl or heteroaryl ; n, m, p and q = independently 1-4.

  该发明提供了公式（I）的氢醌衍生物，制备方法，以及治疗和/或预防例如自身免疫、免疫学、风湿学、血管学、眼科学、纤维化、代谢和胃肠道疾病、神经炎症和神经退行性疾病、肿瘤和癌症相关疾病、激素相关疾病以及由病毒和细菌感染疾病及其并发症引起的免疫疾病的药物组合物和治疗方法。其中：Ra、Rb = H、酰基或芳基烷基；R1 = COOR4、（CH2）nCOOR4、SO3H、（CH2）nSO3H或CONH-R10；R2和R3 = H或R5，但当R2和R3中的一个为R5时，另一个为H；R4 = H、烷基或芳基烷基；R5 = R6、R7或R8；R6 = CONH-R9、CONHCOR9、CONH（CH2）n-R9、CONHCH（COOR4）（CH2）kR9或杂环芳基-R9；k = 0-4；R7 = 可选取代的苯杂环芳基；R8 =（CH2）mX（CH2）pR9；X = O、S、SO2、NH、NAc或N（CH2）qR9；R9 = 可选取代的芳基、杂环芳基或环烷基；R10 = 可选取代的芳基或杂环芳基；n、m、p和q = 独立地为1-4。
• Thermodynamics of the interaction of γ-cyclodextrin and tauro- and glyco-conjugated bile salts
  作者：René Holm、Christian Schönbeck、Sune Askjær、Peter Westh

  DOI：10.1007/s10847-012-0165-1

  日期：2013.2

  The structural differences in the interaction between natural γ-cyclodextrin and bile salts common in rat, dog and man was were investigated by 1H-ROESY and 13C NMR and molecular modeling and the thermodynamic parameters of the reaction by isothermal titration calorimetry. The γ-cyclodextrin was selected based upon its frequent use in drug formulation as excipients to facilitate the solubilisation of drug substances with low aqueous solubility upon oral administration. The NMR studies and the molecular modeling demonstrated an interaction with inclusion of the C-ring of the steroid body of the bile salt and partly inclusion of the B and D ring. A large variation was observed in the stability constants among the investigated bile salt. The variations in the enthalpic and entropic contributions to the overall Gibbs free energy and consequently the stability constants revealed structural differences between the bile salts, where bile salts with a hydroxyl group on C12 has a weaker interaction than the bile salts without the hydroxyl group. Based upon the theoretical calculations of the available surface area the differences observed in the entropic contribution seems to be mainly driven by dehydration effects.

  通过 1H-ROESY 和 13C NMR 以及分子建模研究了天然 γ-环糊精与大鼠、狗和人体内常见胆盐之间相互作用的结构差异，并通过等温滴定量热法研究了反应的热力学参数。之所以选择γ-环糊精，是因为γ-环糊精在药物制剂中常被用作赋形剂，以促进水溶性低的药物物质在口服时的溶解。核磁共振研究和分子建模表明，胆盐的类固醇体 C 环和部分 B 环和 D 环之间存在相互作用。所研究的胆盐在稳定性常数方面存在很大差异。对总体吉布斯自由能的焓贡献和熵贡献的变化以及由此产生的稳定性常数揭示了胆汁盐之间的结构差异，其中 C12 上含有羟基的胆汁盐比不含羟基的胆汁盐的相互作用更弱。根据对可用表面积的理论计算，在熵贡献方面观察到的差异似乎主要是由脱水效应引起的。