N-(olean-3β-hydroxy-11-oxo-12-en-30-oyl)-L-leucine | 912271-66-0

• 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-(olean-3β-hydroxy-11-oxo-12-en-30-oyl)-L-leucine
• 英文别名: N-(L-leucine)-3β-hydroxy-11-oxo-olean-12-en-18β-H-30-amide；(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]-4-methylpentanoic acid
• CAS: 912271-66-0
• 化学式: C₃₆H₅₇NO₅
• 分子量: 583.852
• InChiKey: PWLRUJLKLDQEQC-YCUVPHTGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.5
• 重原子数：
  42
• 可旋转键数：
  5
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.86
• 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-(olean-3β-hydroxy-11-oxo-12-en-30-oyl)-L-leucine 、 2,2-二甲基琥珀酸酐 在 吡啶 、 4-二甲氨基吡啶 作用下， 反应 12.0h， 以65%的产率得到2,2-Dimethyl-succinic acid 4-[(3S,4aR,6aR,6bS,8aS,11S,12aR,14aR,14bS)-11-((S)-1-carboxy-3-methyl-butylcarbamoyl)-4,4,6a,6b,8a,11,14b-heptamethyl-14-oxo-1,2,3,4,4a,5,6,6a,6b,7,8,8a,9,10,11,12,12a,14,14a,14b-icosahydro-picen-3-yl] ester
  参考文献：
  名称：

  Anti-AIDS Agents 69. Moronic Acid and Other Triterpene Derivatives as Novel Potent Anti-HIV Agents

  摘要：

  In a continuing structure-activity relationship study of potent anti-HIV agents, seven new triterpene derivatives were designed, synthesized, and evaluated for in vitro antiviral activity. Among them, moronic acid derivatives 19, 20, and 21 showed significant activity in HIV-1 infected H9 lymphocytes. Compounds 19 and 20 were also evaluated against HIV-1 NL4-3 and drug resistant strains in the MT-4 cell line. Compounds 19 and 20 showed better antiviral profiles than the betulinic acid analogue 8 (PA-457), which has successfully completed a Phase IIa clinical trial. Compound 20 showed potent anti-HIV activity with EC50 values of 0.0085 mu M against NL4-3, 0.021 mu M against PI-R (a multiple protease inhibitor resistant strain), and 0.13 mu M against FHR-2 (an HIV strain resistant to 8). Promising compound 20 has become a new lead for modification, and further development of 20-related compounds as clinical trial candidates is warranted.

  DOI：

  10.1021/jm0601912
• 作为产物：
  描述：

  甘草次酸 在 吡啶 、 氯化亚砜 、 三乙胺 、 三氟乙酸 、 sodium hydroxide 作用下， 以 1,4-二氧六环 、 二氯甲烷 、 水 、 苯 为溶剂， 反应 33.0h， 生成 N-(olean-3β-hydroxy-11-oxo-12-en-30-oyl)-L-leucine
  参考文献：
  名称：

  Synthesis and Antiviral Activity of Amino-Acid Conjugates of Glycyrrhetic Acid

  摘要：

  甘草次酸（GLA）与氨基酸（L-异亮氨酸、-亮氨酸、-缬氨酸和-苯丙氨酸）的共轭物通过酸氯化物法合成，使用酸的甲酯或叔丁酯作为原料。在MDCK细胞培养实验中，GLA与苯丙氨酸的共轭物显示出对甲型流感H1N1/pdm09病毒的高抗病毒活性（ED50 = 4.4 μg/mL，SI = 161）。

  DOI：

  10.1007/s10600-014-0990-0

文献信息

• 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.