3-O-[N-(biphenyl)-p-carbamoyl]oleanolic acid | 1520096-22-3

• 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: 3-O-[N-(biphenyl)-p-carbamoyl]oleanolic acid
• 英文别名: 3-O-[N-(p-biphenyl)carbamoyl]oleanolic acid；(4aS,6aR,6aS,6bR,8aR,10S,12aR,14bS)-2,2,6a,6b,9,9,12a-heptamethyl-10-[(4-phenylphenyl)carbamoyloxy]-1,3,4,5,6,6a,7,8,8a,10,11,12,13,14b-tetradecahydropicene-4a-carboxylic acid
• CAS: 1520096-22-3
• 化学式: C₄₃H₅₇NO₄
• 分子量: 651.93
• InChiKey: FKOAYZWYPHGRBN-ZVAGFZNZSA-N

物化性质

• 沸点：
  703.7±60.0 °C(predicted)
• 密度：
  1.16±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  11.1
• 重原子数：
  48
• 可旋转键数：
  5
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.63
• 拓扑面积：
  75.6
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  齐墩果酸 、 4-联苯异氰酸盐 在 三乙胺 作用下， 以 甲苯 为溶剂， 反应 2.0h， 以29%的产率得到3-O-[N-(biphenyl)-p-carbamoyl]oleanolic acid
  参考文献：
  名称：

  通过靶向Brk / Paxillin / Rac1轴发现齐墩果酸及其类似物作为乳腺癌细胞迁移和侵袭抑制剂的类似物的发现，优化和药理学建模

  摘要：

  生物测定指导的Terminalia bentzoe L.的叶分离甲醇提取物确定了已知的三萜齐墩果酸（1）是其主要的乳腺癌细胞迁移抑制剂。进一步的化学优化，得到了五个新（9 - 12和15）和七个已知的（4 - 8，13，和14）的半合成类似物。测试所有化合物抑制人乳腺癌MDA-MB-231细胞迁移，增殖和侵袭的能力。结果显示3‐ O‐ [ N‐（3′‐氯苯磺酰基）‐氨基甲酰基】‐油酸（11）和3‐O‐ö - [ ñ - （5'-氟苯磺酰基） -氨基甲酰基] -oleanolic酸（12）是在低温的最活跃的命中μ米浓度。Western blot分析表明活性1，11，和12可能至少部分与抑制Brk / Paxillin / Rac1信号通路有关。进行了药理学建模研究，以更好地了解对于抗迁移活性重要的常见结构结合表位。具有最佳体积的缺电子苯环的磺酰基氨基甲酰基部分与改善的活性有关。这项研究是第一个通过靶向Brk

  DOI：

  10.1111/cbdd.12380

文献信息

• Rational design and synthesis of topoisomerase I and II inhibitors based on oleanolic acid moiety for new anti-cancer drugs
  作者：Ahmed Ashour、Saleh El-Sharkawy、Mohamed Amer、Fatma Abdel Bar、Yoshinori Katakura、Tomofumi Miyamoto、Nozomi Toyota、Tran Hai Bang、Ryuichiro Kondo、Kuniyoshi Shimizu

  DOI：10.1016/j.bmc.2013.11.034

  日期：2014.1

  Semisynthetic reactions were conducted on oleanolic acid, a common plant-derived oleanane-type triterpene. Ten rationally designed derivatives of oleanolic acid were synthesized based on docking studies and tested for their topoisomerase I and IIa inhibitory activity. Semisynthetic reactions targeted C-3, C-12, C-13, and C-17. Nine of the synthesized compounds were identified as new compounds. The structures of these compounds were confirmed by spectroscopic methods (1D, 2D NMR and MS). Five oleanolic acid analogues (S2, S3, S5, S7 and S9) showed higher activity than camptothecin (CPT) in the topoisomerase I DNA relaxation assay. Four oleanolic acid analogues (S2, S3, S5 and S6) showed higher activity than etoposide in a topoisomerase II assay. The results indicated that the C12-C13 double bond of the oleanolic acid skeleton is important for the inhibitory activity against both types of topoisomerases, while insertion of a longer chain at either position 3 or 17 increases the activity against topoisomerases by various degrees. Some of the synthesized compounds act as dual inhibitors for both topoisomerase I and IIa. (C) 2013 Elsevier Ltd. All rights reserved.
• Discovery, Optimization, and Pharmacophore Modeling of Oleanolic Acid and Analogues as Breast Cancer Cell Migration and Invasion Inhibitors Through Targeting Brk/Paxillin/Rac1 Axis
  作者：Heba E. Elsayed、Mohamed R. Akl、Hassan Y. Ebrahim、Asmaa A. Sallam、Eman G. Haggag、Amel M. Kamal、Khalid A. El Sayed

  DOI：10.1111/cbdd.12380

  日期：2015.2

  indicated the activity of 1, 11, and 12 might be related, at least in part, to the suppression of Brk/Paxillin/Rac1 signaling pathway. Pharmacophore modeling study was conducted to better understand the common structural binding epitopes important for the antimigratory activity. The sulfonyl carbamoyl moiety with an optimal bulkiness electron‐deficient phenyl ring is associated with improved activity. This

  生物测定指导的Terminalia bentzoe L.的叶分离甲醇提取物确定了已知的三萜齐墩果酸（1）是其主要的乳腺癌细胞迁移抑制剂。进一步的化学优化，得到了五个新（9 - 12和15）和七个已知的（4 - 8，13，和14）的半合成类似物。测试所有化合物抑制人乳腺癌MDA-MB-231细胞迁移，增殖和侵袭的能力。结果显示3‐ O‐ [ N‐（3′‐氯苯磺酰基）‐氨基甲酰基】‐油酸（11）和3‐O‐ö - [ ñ - （5'-氟苯磺酰基） -氨基甲酰基] -oleanolic酸（12）是在低温的最活跃的命中μ米浓度。Western blot分析表明活性1，11，和12可能至少部分与抑制Brk / Paxillin / Rac1信号通路有关。进行了药理学建模研究，以更好地了解对于抗迁移活性重要的常见结构结合表位。具有最佳体积的缺电子苯环的磺酰基氨基甲酰基部分与改善的活性有关。这项研究是第一个通过靶向Brk