3α-acetoxy-4β-amino-11-oxo-24-norurs-12-ene | 872090-58-9

• 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: 3α-acetoxy-4β-amino-11-oxo-24-norurs-12-ene
• 英文别名: [(3R,4R,4aR,6aR,6bS,8aR,11R,12S,12aR,14aR,14bS)-4-amino-4,6a,6b,8a,11,12,14b-heptamethyl-14-oxo-1,2,3,4a,5,6,7,8,9,10,11,12,12a,14a-tetradecahydropicen-3-yl] acetate
• CAS: 872090-58-9
• 化学式: C₃₁H₄₉NO₃
• 分子量: 483.735
• InChiKey: SKGLXMIAUFVHTH-JKUONKRSSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.5
• 重原子数：
  35
• 可旋转键数：
  2
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.87
• 拓扑面积：
  69.4
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3α-acetoxy-4β-amino-11-oxo-24-norurs-12-ene 在 盐酸羟胺 、 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 、 potassium hydroxide 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 22.5h， 生成 N¹-hydroxy-N⁶-(3-α-hydroxy-11-oxo-24-norurs-12-en-4-yl)adipamide
  参考文献：
  名称：

  Design, synthesis and biological evaluation of β-boswellic acid based HDAC inhibitors as inducers of cancer cell death

  摘要：

  The synthesis and bio-evaluation of naturally occurring boswellic acids (BAs) as an alternate CAP for the design of new HDAC inhibitors is described. All the compounds were screened against a panel of human cancer cell lines to identify leads, which were subsequently examined for their potential to inhibit HDACs. The identified lead compound showed IC50 value of 6μm for HDACs, found to induce G1 cell cycle arrest at significantly low concentration (1μM) and caused significant loss in mitochondrial membrane potential at 5 and 10μM. Furthermore, specific interactions of the lead molecule inside the catalytic domain were also studied through in silico molecular modeling.

  DOI：

  10.1016/j.bmcl.2014.08.007
• 作为产物：
  描述：

  乙酰基-11-酮基-beta-乳香酸 在 氯化亚砜 、 sodium azide 、 三氟乙酸 作用下， 以 水 、 丙酮 、 甲苯 为溶剂， 反应 5.0h， 生成 3α-acetoxy-4β-amino-11-oxo-24-norurs-12-ene
  参考文献：
  名称：

  Design, synthesis and biological evaluation of β-boswellic acid based HDAC inhibitors as inducers of cancer cell death

  摘要：

  The synthesis and bio-evaluation of naturally occurring boswellic acids (BAs) as an alternate CAP for the design of new HDAC inhibitors is described. All the compounds were screened against a panel of human cancer cell lines to identify leads, which were subsequently examined for their potential to inhibit HDACs. The identified lead compound showed IC50 value of 6μm for HDACs, found to induce G1 cell cycle arrest at significantly low concentration (1μM) and caused significant loss in mitochondrial membrane potential at 5 and 10μM. Furthermore, specific interactions of the lead molecule inside the catalytic domain were also studied through in silico molecular modeling.

  DOI：

  10.1016/j.bmcl.2014.08.007

文献信息

• Novel analogs of 3-o-acetyl-11-keto-ß-boswellic acid
  申请人：Gokaraju Raju Ganga

  公开号：US20060089409A1

  公开（公告）日：2006-04-27

  This invention relates to novel AKBA analogs of the formula I given below: Where in R 1 , R 2 , R 3 , R 4 and R 5 in each of the said analogs are:— 1. R 1 ═OCHO, R 2 ═H, R 3 ═COOH, R 4 & R 5 ═O 2. R 1 ═OCOCH 2 Cl, R 2 ═H, R 3 ═COOH, R 4 & R 5 ═O 3. R 1 =5′-O-methylgalloyloxy, R 2 ═H, R 3 ═COOH, R 4 & R 5 ═O 4. R 1 ═OCOCH 2 CH 2 COOH, R 2 ═H, R 3 ═COOH, R 4 & R 5 ═O 5. R 1 =8′,9′-Dihydro-4′-hydroxycinnamoyloxy, R 2 ═H, R 3 ═COOH, R 4 & R 5 ═O 6. R 1 =4′-Hydroxycinnamoyloxy, R 2 ═H, R 3 ═COOH, R 4 & R 5 ═O 7. R 1 =3′,4′-Dimethoxycinnamoyloxy, R 2 ═H, R 3 ═COOH, R 4 & R 5 ═O 8. R 1 =3′,4′-Dihydroxy-5′-methoxycinnamoyloxy, R 2 ═H, R 3 COOH, R 4 & R 5 ═O 9. R 1 ═OCOCH 2 NH(tert-BOC), R 2 ═H, R 3 ═COOCH 3 , R 4 & R 5 ═O 10. R 1 ═OCOCH 2 NH 2 HCl, R 2 ═H, R 3 —COOH, R 4 & R 5 ═O 11. R 1 ═OCOCH(CH 3 )NH 2 HCl, R 2 ═H, R 3 ═COOH, R 4 & R 5 ═O 12. R 1 ═H, R 2 ═OH, R 3 ═COOCH 3 , R 4 & R 5 ═O 13. R 1 ═H, R 2 ═Br, R 3 COOCH 3 , R 4 & R 5 ═O 14. R 1 ═CN, R 2 ═H, R 3 ═COOCH 3 , R 4 & R 5 ═O 15. R 1 ═SH, R 2 ═H, R 3 ═COOCH 3 , R 4 & R 5 ═O 16. R 1 & R 2 ═N(OH), R 3 ═COOCH 3 , R 4 & R 5 ═O 17. R 1 & R 2 ═H & OCOCH 3 R 3 ═H, R 4 & R 5 ═O 18. R 1 ═OCOCH 3 , R 2 ═H R 3 ═COOCH 2 CH 2 N(CH 3 ) 2 , R 4 & R 5 ═O 19. R 1 ═OCOCH 3 , R 2 ═H R 3 ═CONH 2 , R 4 & R 5 ═O 20. R 1 ═OCOCH 3 , R 2 ═H, R 3 ═CONHNH 2 , R 4 & R 5 ═O 21. R 1 ═OCOCH 3 , R 2 ═H, R 3 ═CONHCH 2 CH 2 NH 2 , R 4 & R 5 ═O 22. R 1 ═OCOCH 3 , R 2 ═H, R 3 ═CONHCH 2 CH 2 OH, R 4 & R 5 ═O 23. R 1 ═OCOCH 3 , R 2 ═H, R 3 ═CON(CH 2 CH 2 ) 2 NH, R 4 & R 5 ═O 24. R 1 ═OCOCH 3 , R 2 ═H R 3 ═NCO, R 4 & R 5 ═O 25. R 1 ═OCOCH 3 , R 2 ═H R 3 ═NH 2 , R 4 & R 5 ═O 26. R 1 ═OCOCH 3 , R 2 ═H R 3 ═CN, R 4 & R 5 ═O 27. R 1 ═OH, R 2 ═H R 3 ═COOH, R 4 & R 5 ═OH & H These compounds exhibited 5 -Lipoxigenase inhibitory properties and these compounds may be used in pharmaceutical compositions for therapeutic applications against a variety of inflammations and hypersensitivity-based human diseases including asthma, arthritis, bowel diseases such as ulcerative colitis and circulatory disorders such as shock and ischaemia. These compounds also inhibited the growth of Brine Shrimp in cultures, which may be considered as a positive indication for cytotoxicity and antitumor activity.

  本发明涉及下式 I 的新型 AKBA 类似物： 其中 R 1 , R 2 , R 3 , R 4 和 R 5 在上述每种类似物中为 1.R 1 ═OCHO, R 2 H, R 3 ═COOH, R 4 & R 5 ═O 2.R 1 ═OCOCH 2 Cl, R 2 H, R 3 ═COOH, R 4 & R 5 ═O 3.R 1 =5′-O-甲基甲酰氧基，R 2 ═H，R 3 ═COOH，R 4 & R 5 ═O 4.R 1 ═OCOCH 2 CH 2 COOH, R 2 ═H, R 3 ═COOH, R 4 & R 5 ═O 5.R 1 =8′,9′-二氢-4′-羟基肉桂酰氧基，R 2 ═H，R 3 ═COOH，R 4 & R 5 ═O 6.R 1 =4′-羟基肉桂酰氧基，R 2 ═H，R 3 ═COOH，R 4 & R 5 ═O 7.R 1 =3′,4′-二甲氧基肉桂酰氧基，R 2 ═H，R 3 ═COOH，R 4 & R 5 ═O 8.R 1 =3′,4′-二羟基-5′-甲氧基肉桂酰氧基，R 2 ═H，R 3 COOH，R 4 & R 5 ═O 9.R 1 OCOCH 2 NH(叔丁氧羰基)，R 2 H, R 3 ═COOCH 3 , R 4 & R 5 ═O 10.R 1 OCOCH 2 NH 2 HCl, R 2 ═H, R 3 -COOH、R 4 & R 5 ═O 11.R 1 OCOCH(CH 3 )NH 2 HCl, R 2 ═H，R 3 ═COOH, R 4 & R 5 ═O 12.R 1 ═H，R 2 ═OH, R 3 ═COOCH 3 , R 4 & R 5 ═O 13.R 1 ═H, R 2 ═Br，R 3 COOCH 3 , R 4 & R 5 ═O 14.R 1 ═CN，R 2 H, R 3 ═COOCH 3 , R 4 & R 5 ═O 15.R 1 ═SH，R 2 ═H, R 3 ═COOCH 3 , R 4 & R 5 ═O 16.R 1 & R 2 ═N（OH），R 3 ═COOCH 3 , R 4 & R 5 ═O 17.R 1 & R 2 ═H & OCOCH 3 R 3 ═H, R 4 & R 5 ═O 18.R 1 OCOCH 3 , R 2 ═H R 3 ═COOCH 2 CH 2 N(CH 3 ) 2 , R 4 & R 5 ═O 19.R 1 OCOCH 3 , R 2 ═H R 3 ═CONH 2 , R 4 & R 5 ═O 20.R 1 OCOCH 3 , R 2 H, R 3 ═CONHNH 2 , R 4 & R 5 ═O 21.R 1 OCOCH 3 , R 2 H, R 3 ═CONHCH 2 CH 2 NH 2 , R 4 & R 5 ═O 22.R 1 OCOCH 3 , R 2 H, R 3 ═CONHCH 2 CH 2 OH，R 4 & R 5 ═O 23.R 1 OCOCH 3 , R 2 H, R 3 ═CON(CH 2 CH 2 ) 2 NH, R 4 & R 5 ═O 24.R 1 OCOCH 3 , R 2 ═H R 3 ═NCO, R 4 & R 5 ═O 25.R 1 OCOCH 3 , R 2 ═H R 3 ═NH 2 , R 4 & R 5 ═O 26.R 1 OCOCH 3 , R 2 ═H R 3 ═CN，R 4 & R 5 ═O 27.R 1 ═OH, R 2 ═H R 3 ═COOH, R 4 & R 5 ═OH & H 这些化合物表现出 5 -脂氧化酶抑制特性，这些化合物可用于药物组合物，以治疗各种炎症和超敏性人类疾病，包括哮喘、关节炎、肠道疾病（如溃疡性结肠炎）以及循环系统疾病（如休克和缺血）。这些化合物还能抑制盐水虾在培养物中的生长，可视为细胞毒性和抗肿瘤活性的积极迹象。
• Analogues of boswellic acids as inhibitors of pro-inflammatory cytokines TNF-α and IL-6
  作者：Simmi Sharma、Shilpa Gupta、Vidushi Khajuria、Asha Bhagat、Zabeer Ahmed、Bhahwal Ali Shah

  DOI：10.1016/j.bmcl.2015.11.035

  日期：2016.1

  A library of boswellic acid analogues were synthesized and tested for their anti-inflammatory potential on key inflammatory mediators, TNF-alpha and IL-6. The study led to the identification of lead compounds showing significant inhibition of the cytokines, TNF-alpha and IL-6 both in vitro and in vivo. (C) 2015 Elsevier Ltd. All rights reserved.
• Cytotoxic and apoptotic activities of novel amino analogues of boswellic acids
  作者：Bhahwal A. Shah、Ajay Kumar、Pankaj Gupta、Madhunika Sharma、Vijay K. Sethi、Ajit K. Saxena、Jaswant Singh、Ghulam N. Qazi、Subhash C. Taneja

  DOI：10.1016/j.bmcl.2007.10.011

  日期：2007.12

  4-Amino analogues prepared from beta-boswellic acid and 11-keto-beta-boswellic acid, wherein the carboxyl group in ursane nucleus was replaced by an amino function via Curtius reaction, displayed improved cytotoxicity than the parent molecules. The same molecules also exhibited apoptotic activity by inducing DNA fragmentation. (c) 2007 Elsevier Ltd. All rights reserved.
• NOVEL ANALOGS OF 3-O-ACETYL-11-KETO-BETA-BOSWELLIC ACID
  申请人：LAILA NUTRACEUTICALS

  公开号：EP1765761B1

  公开（公告）日：2013-04-03
• USES OF ANALOGS OF 3-O-ACETYL-11-KETO-BETA-BOSWELLIC ACID
  申请人：Gokaraju Ganga Raju

  公开号：US20090318551A1

  公开（公告）日：2009-12-24

  This invention relates to novel AKBA analogs of the formula I given below: Where in R 1 , R 2 , R 3 , R 4 and R 5 in each of the said analogs are: 1. R 1 ═OCHO, R 2 ═H, R 3 ═COOH, R 4 & R 5 ═O 2. R 1 ═OCOCH 2 Cl, R 2 ═H, R 3 ═COOH, R 4 & R 5 ═O 3. R 1 =5′-O-methylgalloyloxy, R 2 ═H, R 3 ═COOH, R 4 & R 5 ═O 4. R 1 ═OCOCH 2 CH 2 COOH, R 2 ═H, R 3 ═COOH, R 4 & R 5 ═O 5. R 1 =8′,9′-Dihydro-4′-hydroxycinnamoyloxy, R 2 ═H, R 3 ═COOH, R 4 & R 5 ═O 6. R 1 =4′-Hydroxycinnamoyloxy, R 2 ═H, R 3 ═COOH, R 4 & R 5 ═O 7. R 1 =3′,4′-Dimethoxycinnamoyloxy, R 2 ═H, R 3 ═COOH, R 4 & R 5 ′O 8. R 1 =3′,4′-Dihydroxy-5′-methoxycinnamoyloxy, R 2 ═H, R 3 ═COOH, R 4 & R 5 ═O 9. R 1 ═OCOCH 2 NH(tert-BOC), R 2 ═H, R 3 ═COOCH 3 , R 4 & R 5 ═O 10. R 1 ═OCOCH 2 NH 2 HCl, R 2 ═H, R 3 ═COOH, R 4 & R 5 ═O 11. R 1 ═OCOCH(CH 3 )NH 2 HCl, R 2 ═H, R 3 ═COOH, R 4 & R 5 ═O 12. R 1 ═H, R 2 ═OH, R 3 ═COOCH 3 , R 4 & R 5 ═O 13. R 1 ═H, R 2 ═Br, R 3 ═COOCH 3 , R 4 & R 5 ═O 14. R 1 ═CN, R 2 ═H, R 3 ═COOCH 3 , R 4 & R 5 ═O 15. R 1 ═SH, R 2 ═H, R 3 ═COOCH 3 , R 4 & R 5 ═O 16. R 1 & R 2 ═N(OH), R 3 ═COOCH 3 , R 4 & R 5 ═O 17. R 1 & R 2 ═H & OCOCH 3 R 3 ═H, R 4 & R 5 ═O 18. R 1 ═OCOCH 3 , R 2 ═H, R 3 ═COOCH 2 CH 2 N(CH 3 ) 2 , R 4 & R 5 ═O 19. R 1 ═OCOCH 3 , R 2 ═H R 3 ═CONH 2 , R 4 & R 5 ═O 20. R 1 ═OCOCH 3 , R 2 ═H, R 3 ═CONHNH 2 , R 4 & R 5 50 O 21. R 1 ═OCOCH 3 , R 2 ═H, R 3 ═CONHCH 2 CH 2 NH 2 , R 4 & R 5 ═O 22. R 1 ═OCOCH 3 , R 2 ═H, R 3 ═CONHCH 2 CH 2 OH, R 4 & R 5 ═O 23. R 1 ═OCOCH 3 , R 2 ═H, R 3 ═CON(CH 2 CH 2 ) 2 NH, R 4 & R 5 ═O 24. R 1 ═OCOCH 3 , R 2 ═H R 3 ═NCO, R 4 & R 5 ═O 25. R 1 ═OCOCH 3 , R 2 ═H R 3 ═NH 2 , R 4 & R 5 ═O 26. R 1 ═OCOCH 3 , R 2 ═H R 3 ═CN, R 4 & R 5 ═O 27. R 1 ═OH, R 2 ═H R 3 ═COOH, R 4 & R 5 ═OH & H These compounds exhibited 5-Lipoxigenase inhibitory properties and these compounds may be used in pharmaceutical compositions for therapeutic applications against a variety of inflammations and hypersensitivity-based human diseases including asthma, arthritis, bowel diseases such as ulcerative colitis and circulatory disorders such as shock and ischaemia. These compounds also inhibited the growth of Brine Shrimp in cultures, which may be considered as a positive indication for cytotoxicity and antitumor activity.