N-(3β-hydroxy-11,30-dioxo-18β-olean-12-en-30-yl)-L-alanine

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 异戊烯醇脂质
• 英文名称: N-(3β-hydroxy-11,30-dioxo-18β-olean-12-en-30-yl)-L-alanine
• 英文别名: (2S)-2-[[(2S,4aS,6aR,6aS,6bR,8aR,10S,12aS,14bR)-10-hydroxy-2,4a,6a,6b,9,9,12a-heptamethyl-13-oxo-3,4,5,6,6a,7,8,8a,10,11,12,14b-dodecahydro-1H-picene-2-carbonyl]amino]propanoic acid
• 化学式: C₃₃H₅₁NO₅
• 分子量: 541.772
• InChiKey: CFQZRHIRZLFMGZ-UMBQQECESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.2
• 重原子数：
  39
• 可旋转键数：
  3
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.85
• 拓扑面积：
  104
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  N-(3β-hydroxy-11,30-dioxo-18β-olean-12-en-30-yl)-L-alanine 、 3-氨基-2,2,5,5-四甲基-1-吡咯烷酮 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以72%的产率得到
  参考文献：
  名称：

  Synthesis and biological evaluation of novel spin labeled 18β-glycyrrhetinic acid derivatives

  摘要：

  Eighteen novel spin-labeled 18 beta-glycyrrhetinic acid (GA) derivatives were designed, synthesized, and evaluated for cytotoxicity against four human tumor cell lines (A-549, DU-145, KB and KBvin). Most of the derivatives showed more significant cytotoxicity than that of the parent compound GA. The best compound, 6j, with a tryptophan amino moiety and piperidine nitroxyl radical showed GI(50) values of 13.7-15.0 mu M, and was fivefold more potent than GA. In a mechanism of action study, compound 7a was confirmed as a 20S proteasome inhibitor in both in vitro and cell-based assays. These findings support further optimization efforts based on 18 beta-GA as a lead compound to develop potential anticancer drug candidates. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.10.041
• 作为产物：
  描述：

  甘草次酸 在 三乙胺 4-二甲氨基吡啶 、 sodium hydroxide 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 为溶剂， 反应 2.0h， 生成 N-(3β-hydroxy-11,30-dioxo-18β-olean-12-en-30-yl)-L-alanine
  参考文献：
  名称：

  Novel 18β-glycyrrhetinic acid analogues as potent and selective inhibitors of 11β-hydroxysteroid dehydrogenases

  摘要：

  Extensive structural modifications to the 18beta-glycyrrhetinic acid template are described and their effects on the SAR of the 11beta-hydroxysteroid dehydrogenase isozymes type 1 and 2 from the rat are investigated. Isoform selective inhibitors have been discovered and compound 7 N-(2-hydroxyethyl)-3beta-hydroxy-11-oxo-18beta-olean-12-en-30-oic acid amide is highlighted as a very potent selective inhibitor of 11beta-hydroxysteroid dehydrogenase 2 with an IC50 = 4 pM. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2004.06.008

文献信息

• Novel 18β-glycyrrhetinic acid analogues as potent and selective inhibitors of 11β-hydroxysteroid dehydrogenases
  作者：Xiangdong Su、Harshani Lawrence、Dharshini Ganeshapillai、Adrian Cruttenden、Atul Purohit、Michael J Reed、Nigel Vicker、Barry V.L Potter

  DOI：10.1016/j.bmc.2004.06.008

  日期：2004.8

  Extensive structural modifications to the 18beta-glycyrrhetinic acid template are described and their effects on the SAR of the 11beta-hydroxysteroid dehydrogenase isozymes type 1 and 2 from the rat are investigated. Isoform selective inhibitors have been discovered and compound 7 N-(2-hydroxyethyl)-3beta-hydroxy-11-oxo-18beta-olean-12-en-30-oic acid amide is highlighted as a very potent selective inhibitor of 11beta-hydroxysteroid dehydrogenase 2 with an IC50 = 4 pM. (C) 2004 Elsevier Ltd. All rights reserved.
• Synthesis and biological evaluation of novel spin labeled 18β-glycyrrhetinic acid derivatives
  作者：Yingqian Liu、Keduo Qian、Chih-Ya Wang、Chin-Ho Chen、Xiaoming Yang、Kuo-Hsiung Lee

  DOI：10.1016/j.bmcl.2012.10.041

  日期：2012.12

  Eighteen novel spin-labeled 18 beta-glycyrrhetinic acid (GA) derivatives were designed, synthesized, and evaluated for cytotoxicity against four human tumor cell lines (A-549, DU-145, KB and KBvin). Most of the derivatives showed more significant cytotoxicity than that of the parent compound GA. The best compound, 6j, with a tryptophan amino moiety and piperidine nitroxyl radical showed GI(50) values of 13.7-15.0 mu M, and was fivefold more potent than GA. In a mechanism of action study, compound 7a was confirmed as a 20S proteasome inhibitor in both in vitro and cell-based assays. These findings support further optimization efforts based on 18 beta-GA as a lead compound to develop potential anticancer drug candidates. (C) 2012 Elsevier Ltd. All rights reserved.