3α,7α-dihydroxy-5β-cholan-24-oic acid 2,5-dioxopyrrolidin-1-yl ester | 174069-12-6

• 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: 3α,7α-dihydroxy-5β-cholan-24-oic acid 2,5-dioxopyrrolidin-1-yl ester
• 英文别名: chenodeoxycholic acid succinimidyl ester；(2,5-dioxopyrrolidin-1-yl) (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]pentanoate
• CAS: 174069-12-6
• 化学式: C₂₈H₄₃NO₆
• 分子量: 489.653
• InChiKey: ZPYAYMINPDNAPT-YJOWQZBFSA-N

物化性质

• 沸点：
  608.0±61.0 °C(Predicted)
• 密度：
  1.23±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  35
• 可旋转键数：
  6
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.89
• 拓扑面积：
  104
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  3α,7α-dihydroxy-5β-cholan-24-oic acid 2,5-dioxopyrrolidin-1-yl ester 在 potassium carbonate 、 三乙胺 、 聚甘氨酸 作用下， 以 二甲基亚砜 、 N,N-二甲基甲酰胺 为溶剂， 反应 8.0h， 生成
  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 、 O-(N-succinimidyl)-N,N,N',N'-tetramethyluronium tetrafluoroborate 在 N,N-二异丙基乙胺 作用下， 以 1,4-二氧六环 、 水 、 N,N-二甲基甲酰胺 为溶剂， 生成 3α,7α-dihydroxy-5β-cholan-24-oic acid 2,5-dioxopyrrolidin-1-yl ester
  参考文献：
  名称：

  Design of novel synthetic MTS conjugates of bile acids for site-directed sulfhydryl labeling of cysteine residues in bile acid binding and transporting proteins

  摘要：

  The purpose of this study was to design bile acid-containing methanethiosulfonate (MTS) agents with appropriate physical attributes to effectively modify the cysteine residues present in the human apical sodium-dependent bile acid transporter. Four physical properties including surface area, molecular volume, Clog P, and dipole moment were calculated for each semiempirically optimized structure of NITS compounds. The specificity of the synthesized bile acid-MTS conjugate toward native cysteines and putative bile acid interacting domains of hASBT was supported by the effect of 1 mM cholyl-MTS, cholylglycyl-MTS, and 3-amino-cholyl-MTS on uptake activity, that displayed a significant decrease in TCA affinity (K-T = 69.9 +/- 4.5, 69.01 +/- 6.2, and 63.24 +/- 0.26 mu M and J(max) = 35.8 +/- 0.3, 24.03 +/- 1.22, 46.49 +/- 5.01 pmol mg protein min(-1), respectively). These compounds prove to be effective tools in probing the structural and functional effects of cysteine residues in bile acid binding and transporting proteins. (C) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2005.12.050

文献信息

• Synthesis and Biological Activity of Some Bile Acid-Based Camptothecin Analogues
  作者：Xingnuo Li、Tengfei Zhao、Dongping Cheng、Chu Chu、Shengqiang Tong、Jizong Yan、Qing-Yong Li

  DOI：10.3390/molecules19033761

  日期：——

  In an effort to decrease the toxicity of camptothecin (CPT) and improve selectivity for hepatoma and colon cancer cells, bile acid groups were introduced into the CPT 20 or 10 positions, resulting in the preparation of sixteen novel CPT-bile acid analogues. The compounds in which a bile acid group was introduced at the 20-hydroxyl group of CPT showed better cytotoxic selectivity for human hepatoma and colon cancer cells than for human breast cancer cells. Fluorescence microscopy analysis demonstrated that one compound (E2) entered human hepatoma cells more effectively than it did human breast cancer cells. Compound G4 exhibited the best anti-tumour activity in vivo. These results suggested that introduction of a bile acid group at the 20-position of CPT could decrease toxicity in vivo and improve selectivity for hepatoma cells.

  为了降低喜树碱（CPT）的毒性并提高其对肝癌和结肠癌细胞的选择性，将胆酸基团引入到CPT的20位或10位，合成了十六种新颖的CPT-胆酸类似物。在CPT的20-羟基位置引入胆酸基团的化合物显示出比人乳腺癌细胞更好的对人肝癌和结肠癌细胞的细胞毒选择性。荧光显微镜分析表明，一种化合物（E2）对人肝癌细胞的进入效果比对人乳腺癌细胞更有效。化合物G4在体内显示出最佳的抗肿瘤活性。这些结果表明，在CPT的20位引入胆酸基团可以降低体内的毒性并提高对肝癌细胞的选择性。
• [EN] IMMUNOMODULATORS<br/>[FR] IMMUNOMODULATEURS
  申请人：BRISTOL MYERS SQUIBB CO

  公开号：WO2021188480A1

  公开（公告）日：2021-09-23

  In accordance with the present disclosure, compounds have been discovered that bind to PD-L1 and are capable of inhibiting the interaction of PD-L1 with PD-1 and CD80. These macrocyclic compounds exhibit in vitro immunomodulatory efficacy thus making them therapeutic candidates for the treatment of various diseases including cancer and infectious diseases.

  根据本公开，已经发现了一些能够结合PD-L1并能够抑制PD-L1与PD-1和CD80相互作用的化合物。这些大环化合物在体外表现出免疫调节疗效，因此成为治疗各种疾病，包括癌症和传染病的治疗候选物。
• Synthesis, Characterization, and Saccharide Binding Studies of Bile Acid − Porphyrin Conjugates
  作者：Juha Koivukorpi、Elina Sievänen、Erkki Kolehmainen、Vladimír Král

  DOI：10.3390/12010013

  日期：——

  Synthesis and characterization of bile acid-porphyrin conjugates (BAPs) are reported. Binding of saccharides with BAPs in aqueous methanol was studied by monitoring changes in the visible absorption spectral of the porphyrin-moieties. Although these studies clearly showed absorbance changes, suggesting quite high if non-selective binding, the mass spectral studies do not unambiguously support these results.

  报告了胆汁酸-卟啉缀合物 (BAP) 的合成和表征。通过监测卟啉部分可见吸收光谱的变化，研究了甲醇水溶液中糖类与 BAP 的结合。尽管这些研究清楚地显示吸光度变化，表明如果非选择性结合则相当高，但质谱研究并没有明确支持这些结果。
• Li; Gao; Qiu, Letters in drug design and discovery, 2011, vol. 8, # 9, p. 698 - 703
  作者：Li、Gao、Qiu、Zu、Su、He、Deng

  DOI：——

  日期：——
• Syntheses and structural study of bile acid amidoalcohols
  作者：Arto Valkonen、Manu Lahtinen、Erkki Kolehmainen

  DOI：10.1016/j.steroids.2008.06.006

  日期：2008.11

  Preparation, structural and thermoanalytical characterization of fourteen N-hydroxyalkyl 5 beta-cholan-24-amides have been performed in this study. The utilized techniques include liquid state and CP-MAS C-13 NMR spectroscopy, thermogravimetry, differential scanning calorimetry, and also powder and single crystal X-ray crystallography. The results were discussed and compared to each other and also to previous findings on similar compounds. One pure hydrate form was obtained. Six new single crystal structures were determined, including one hydrated chloroform solvate. Decomposition temperatures were found to correlate with the side chain length, and the number of the hydroxyl groups. The spatial direction of the groups in the steroid skeleton was also found to be relevant in predicting the thermal properties of bile acid amidoalcohols studied. (C) 2008 Elsevier Inc. All rights reserved.