24-piperazine-3α,7β-dihydroxy-5β-cholanamide | 1260542-91-3

• 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: 24-piperazine-3α,7β-dihydroxy-5β-cholanamide
• 英文别名: 24-Piperazine-3alpha,7beta-dihydroxy-5beta-cholanamide；(4R)-4-[(3R,5S,7S,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]-1-piperazin-1-ylpentan-1-one
• CAS: 1260542-91-3
• 化学式: C₂₈H₄₈N₂O₃
• 分子量: 460.701
• InChiKey: VCLJBBKXNZUFGM-QUKDRKDGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  33
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.96
• 拓扑面积：
  72.8
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  24-piperazine-3α,7β-dihydroxy-5β-cholanamide 在 N,N-二异丙基乙胺 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 作用下， 以 二氯甲烷 为溶剂， 反应 11.0h， 生成 (4R)-4-((3R,5S,7S,10S,13R)-3,7-dihydroxy-10,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthren-17-yl)-1-(4-((Z)-3-(4-hydroxy-3-methoxyphenyl)acryloyl)piperazin-1-yl)pentan-1-one
  参考文献：
  名称：

  通过抑制 Akt/NF-κB 和 MAPK 信号通路来设计、合成和评估熊去氧胆酸-肉桂酸杂化物作为潜在抗炎剂的作用

  摘要：

  设计并合成了一系列熊去氧胆酸（UDCA）-肉桂酸杂化物。通过评估这些衍生物对LPS诱导的RAW264.7巨噬细胞中一氧化氮产生的抑制作用来筛选这些衍生物的抗炎活性。初步得出构效关系。其中2m对NO的抑制活性最好（IC 50  = 7.70 μM），且无明显毒性。进一步研究发现，2m显着降低TNF-α、IL-1β、IL-6和PGE2的水平，下调iNOS和COX-2的表达。初步机制研究表明2m的抗炎活性与抑制Akt/NF-κB和MAPK信号通路有关。此外， 2m还可以减少 LPS 诱导的体内炎症性疾病小鼠模型的炎症。简而言之，我们的研究结果表明2m可能作为进一步开发抗炎药物的新先导化合物。

  DOI：

  10.1016/j.ejmech.2023.115785
• 作为产物：
  描述：

  熊去氧胆酸 在 氯化亚砜 、 高氯酸 、 sodium methylate 、 三乙胺 、 三氟乙酸 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 7.0h， 生成 24-piperazine-3α,7β-dihydroxy-5β-cholanamide
  参考文献：
  名称：

  Ursodeoxycholic Acid Amides As Novel Glucocorticoid Receptor Modulators

  摘要：

  Ursodeoxycholic acid (UDCA) is used for the treatment of hepatic inflammatory diseases Recent studies have shown that UDCA's biological effects are partly glucocorticoid receptor (GR) mediated UDCA derivatives were synthesized and screened for ability to induce GR translocation in a high content analysis assay using the esophageal cancel SKGT-4 cell line UDCA derivatives induced GR translocation in a time dependent manner with equal efficacy to that of dexamethasone (Dex) and with greatly increased potency relative to UDCA The cyclopropylamide la suppressed TNF-alpha Induced NF-kappa B activity and it induced GRE transactivation la was unable to displace Dex from the GR ligand binding domain (LBD) in a competition experiment but was capable of coactivator recruitment in a time-resolved fluorescence energy transfer assay (TR-FRET) This represents a novel mechanism of action for a GR modulator These derivatives could result in a new class of GR modulators

  DOI：

  10.1021/jm100860s

文献信息

• 熊去氧胆酸类化合物及其制法、药物组合物和应用
  申请人：中国医学科学院药用植物研究所

  公开号：CN116854762A

  公开（公告）日：2023-10-10

  本发明公开了一种熊去氧胆酸类化合物及制法、药物组合物和应用。该化合物结构如式1，还包含其异立体异构体、几何异构体、互变异构体、氘代化合物、药学上可接受的盐或它们的混合物。该类化合物对炎症细胞具有高效的抑制作用并显著抑制炎症介质生成，同时对正常细胞的活力无明显影响，具有较低的细胞毒性，适于制备为抗炎药物；并且该类化合物制备方法通用性强，利于结构拓展。#imgabs0#
• Ursodeoxycholic Acid Amides As Novel Glucocorticoid Receptor Modulators
  作者：Ruchika Sharma、David Prichard、Ferenc Majer、Anne-Marie Byrne、Dermot Kelleher、Aideen Long、John F. Gilmer

  DOI：10.1021/jm100860s

  日期：2011.1.13

  Ursodeoxycholic acid (UDCA) is used for the treatment of hepatic inflammatory diseases Recent studies have shown that UDCA's biological effects are partly glucocorticoid receptor (GR) mediated UDCA derivatives were synthesized and screened for ability to induce GR translocation in a high content analysis assay using the esophageal cancel SKGT-4 cell line UDCA derivatives induced GR translocation in a time dependent manner with equal efficacy to that of dexamethasone (Dex) and with greatly increased potency relative to UDCA The cyclopropylamide la suppressed TNF-alpha Induced NF-kappa B activity and it induced GRE transactivation la was unable to displace Dex from the GR ligand binding domain (LBD) in a competition experiment but was capable of coactivator recruitment in a time-resolved fluorescence energy transfer assay (TR-FRET) This represents a novel mechanism of action for a GR modulator These derivatives could result in a new class of GR modulators
• Design, synthesis and evaluation of ursodeoxycholic acid-cinnamic acid hybrids as potential anti-inflammatory agents by inhibiting Akt/NF-κB and MAPK signaling pathways
  作者：Xiaoxue Li、Yue Hu、Bingxin He、Lingyu Li、Yu Tian、Yingjie Xiao、Hai Shang、Zhongmei Zou

  DOI：10.1016/j.ejmech.2023.115785

  日期：2023.11

  acid hybrids were designed and synthesized. The anti-inflammatory activity of these derivatives was screened through evaluating their inhibitory effects of LPS-induced nitric oxide production in RAW264.7 macrophages. The preliminary structure-activity relationship was concluded. Among them, 2m showed the best inhibitory activity against NO (IC50 = 7.70 μM) with no significant toxicity. Further study revealed

  设计并合成了一系列熊去氧胆酸（UDCA）-肉桂酸杂化物。通过评估这些衍生物对LPS诱导的RAW264.7巨噬细胞中一氧化氮产生的抑制作用来筛选这些衍生物的抗炎活性。初步得出构效关系。其中2m对NO的抑制活性最好（IC 50  = 7.70 μM），且无明显毒性。进一步研究发现，2m显着降低TNF-α、IL-1β、IL-6和PGE2的水平，下调iNOS和COX-2的表达。初步机制研究表明2m的抗炎活性与抑制Akt/NF-κB和MAPK信号通路有关。此外， 2m还可以减少 LPS 诱导的体内炎症性疾病小鼠模型的炎症。简而言之，我们的研究结果表明2m可能作为进一步开发抗炎药物的新先导化合物。