1-methyl-9-(3-phenyl-propyl)-β-carboline-7-ol | 1015792-02-5

• 分子结构分类: 有机化合物 - 生物碱及其衍生物 - 哈马拉生物碱
• 英文名称: 1-methyl-9-(3-phenyl-propyl)-β-carboline-7-ol
• 英文别名: 1-methyl-9-(3-phenylpropyl)-β-carbolin-7-ol
• CAS: 1015792-02-5
• 化学式: C₂₁H₂₀N₂O
• 分子量: 316.403
• InChiKey: ZVOSDQGCCUGOLR-UHFFFAOYSA-N

物化性质

• 熔点：
  258-259 °C(Solv: ethanol (64-17-5))
• 沸点：
  545.8±50.0 °C(Predicted)
• 密度：
  1.17±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.84
• 重原子数：
  24.0
• 可旋转键数：
  4.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  38.05
• 氢给体数：
  1.0
• 氢受体数：
  3.0

反应信息

• 作为反应物：
  描述：

  1-methyl-9-(3-phenyl-propyl)-β-carboline-7-ol 在 盐酸 、 sodium hydride 、 sodium iodide 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 2.0h， 生成 1-methyl-9-phenylpropyl-7-(4-(1-(3-pyridyl)-β-carboline-9-yl)butoxy)-β-carboline hydrochloride
  参考文献：
  名称：

  不对称二聚β-咔啉衍生物作为潜在抗肿瘤药的合成及其构效关系

  摘要：

  合成了一系列新的不对称的二聚β-咔啉，它们在吲哚氮和氨苄基氧之间具有一个4-6个亚甲基单元的间隔。通过光谱和分析研究证实了所有新型合成化合物的结构。筛选所有合成的化合物对九种癌细胞系的体外细胞毒活性。结果表明，化合物7c，7o和7s对测试的肿瘤细胞系表现出最高的细胞毒活性，IC 50值小于20μM。还评估了所选化合物在小鼠中的急性毒性和抗肿瘤功效，并且化合物7o表现出有效的抗肿瘤活性，肿瘤抑制率超过40％。伤口愈合试验显示了HT-29细胞运动性的特定损伤，这提示了化合物7o的抗转移潜力。此外，化合物7o在鸡绒膜尿囊膜（CAM）分析中具有明显的血管生成抑制作用。初步的结构-活性关系（SAR）分析表明：（1）吲哚环N 9位的3-苯基丙基取代基是最合适的产生有效细胞毒性剂的基团；（2）间隔物长度影响抗肿瘤能力，并且四个亚甲基单元是更有利的。

  DOI：

  10.1016/j.ejmech.2018.02.003
• 作为产物：
  描述：

  肉叶云香碱 在 氢溴酸 、 sodium hydride 、 溶剂黄146 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 1-methyl-9-(3-phenyl-propyl)-β-carboline-7-ol
  参考文献：
  名称：

  不对称二聚β-咔啉衍生物作为潜在抗肿瘤药的合成及其构效关系

  摘要：

  合成了一系列新的不对称的二聚β-咔啉，它们在吲哚氮和氨苄基氧之间具有一个4-6个亚甲基单元的间隔。通过光谱和分析研究证实了所有新型合成化合物的结构。筛选所有合成的化合物对九种癌细胞系的体外细胞毒活性。结果表明，化合物7c，7o和7s对测试的肿瘤细胞系表现出最高的细胞毒活性，IC 50值小于20μM。还评估了所选化合物在小鼠中的急性毒性和抗肿瘤功效，并且化合物7o表现出有效的抗肿瘤活性，肿瘤抑制率超过40％。伤口愈合试验显示了HT-29细胞运动性的特定损伤，这提示了化合物7o的抗转移潜力。此外，化合物7o在鸡绒膜尿囊膜（CAM）分析中具有明显的血管生成抑制作用。初步的结构-活性关系（SAR）分析表明：（1）吲哚环N 9位的3-苯基丙基取代基是最合适的产生有效细胞毒性剂的基团；（2）间隔物长度影响抗肿瘤能力，并且四个亚甲基单元是更有利的。

  DOI：

  10.1016/j.ejmech.2018.02.003

文献信息

• Synthesis of harmine-nitric oxide donor derivatives as potential antitumor agents
  作者：Zhezhe Li、Yipaerguli Apizi、Chengzhong Zhang、Zhaozhi Wang、Hongji He、Xiaoya Li、Yina Zhu、Jishun Yang、Liang Xiao、Mei Wang

  DOI：10.1016/j.bmcl.2022.128698

  日期：2022.6

  To further improve the anti-tumor activity of Harmine (HM), we took the hybridization approach and synthesized harmine derivatives-furoxan hybrids containing nitric oxide (NO) releasing parts by connecting NO donors with anti-tumor active fragments to harmine. Then, the synthesized compounds were evaluated for their in vitro cytotoxicity against five human cancer cell lines. Among them, compound 10

  为了进一步提高Harmine（HM）的抗肿瘤活性，我们采用杂交的方法，通过将NO供体与抗肿瘤活性片段连接到harmine，合成了含有一氧化氮（NO）释放部分的harmine衍生物-呋喃杂化物。然后，评估合成的化合物对五种人类癌细胞系的体外细胞毒性。其中，化合物10对HepG2的抗增殖活性最强（IC 50  = 1.79 µM）。此外，化合物10在体外产生高水平的NO ，证实NO的释放与抗增殖活性密切相关。此外，化合物10还表现出良好的等离子体稳定性。最后，我们还初步研究了化合物10对小鼠的急性毒性，并通过Caco-2细胞通透性测定评估了化合物10的吸收。简而言之，新的harmine衍生物-呋喃杂化物的显着生物学特性可能使它们成为人类癌症干预的有希望的候选者。
• 一种去氢骆驼蓬碱衍生物及其制备方法和应用
  申请人：新疆医科大学

  公开号：CN114133390A

  公开（公告）日：2022-03-04

  本发明公开了一种去氢骆驼蓬碱衍生物及其制备方法和应用，属于药物化学领域。本发明通过对去氢骆驼蓬碱(HM)进行结构修饰后与NO供体结合形成新的NO供体‑去氢骆驼蓬碱衍生物。NO供体‑去氢骆驼蓬碱衍生物能够在肿瘤细胞内释放大量NO，随着NO释放的增多，选择性地在肿瘤细胞中的抗增殖活性明显增强，而对正常细胞影响较小。相比较原料药HM和NO供体，新化合物NO供体‑去氢骆驼蓬碱衍生物的抗癌细胞增殖作用明显增强。
• Synthesis and structure–activity relationships of harmine derivatives as potential antitumor agents
  作者：Rihui Cao、Wenxi Fan、Liang Guo、Qin Ma、Guoxian Zhang、Jianru Li、Xuemei Chen、Zhenghua Ren、Liqin Qiu

  DOI：10.1016/j.ejmech.2012.11.045

  日期：2013.2

  Harmine, a naturally occurring beta-carboline alkaloid, showed good antitumor activities together with remarkable neurotoxic effects in animal models. In order to search for novel leading compounds endowed with better antitumor activities and less neurotoxicities, a series of harmine derivatives were designed and synthesized by modification of position-2, 7 and 9 of beta-carboline nucleus, and their cytotoxic activities against human tumor cell lines were investigated. Acute toxicities and antitumor activities of the selected compounds in mice were also evaluated. Structure activity relationships studies confirmed that (1) the 7-methoxy structural moiety was the pharmacophore responsible for the neurotoxic effects of this class of compounds; (2) the substituents in position-2 and 9 played a vital role in modulation of their antitumor activities. (C) 2012 Elsevier Masson SAS. All rights reserved.
• Design, synthesis and 3D-QSAR of β-carboline derivatives as potent antitumor agents
  作者：Rihui Cao、Xiangdong Guan、Buxi Shi、Zhiyong Chen、Zhenhua Ren、Wenlie Peng、Huacan Song

  DOI：10.1016/j.ejmech.2010.02.036

  日期：2010.6

  In a continuing effort to develop novel beta-carbolines endowed with better pharmacological profiles, a series of beta-carboline derivatives were designed and synthesized based on the previously developed SARs. Cytotoxicities in vitro of these compounds against a panel of human tumor cell lines were also investigated. The results demonstrated that the N(2)-benzylated beta-carbolinium bromides 56-60 represented the most potent compounds with IC(50) values lower than 10 mu M. The application of 3D-QSAR to these compounds explored the structural basis for their biological activities. CoMFA (q(2) = 0.513, r(2) = 0.862) and CoMSIA (q(2) = 0.503, r(2) = 0.831) models were developed for a set of 47 beta-carbolines. The results indicated that the antitumor pharmacophore of these molecules were marked at position-1, -2, -3, -7 and -9 of beta-carboline ring.
• Synthesis and cytotoxic activities of 1-benzylidine substituted β-carboline derivatives
  作者：Rihui Cao、Wei Yi、Qifeng Wu、Xiangdong Guan、Manxiu Feng、Chunming Ma、Zhiyong Chen、Huacan Song、Wenlie Peng

  DOI：10.1016/j.bmcl.2008.10.043

  日期：2008.12

  A series of new beta-carboline derivatives, bearing a benzylidine substituent at position-1, has been prepared and evaluated in vitro against a panel of human cell lines. The N-2-benzylated beta-carbolinium bromates represented the most interesting cytotoxic activities. In particular, compounds 19 were found to be the most potent compounds with IC50 values lower than 5 mu M against 10 strains human tumor cell lines. These results confirmed that the N-2-benzyl substituent on the beta-carboline ring played an important role in the modulation of the cytotoxic activities and suggested that further development of such compounds may be interest. (C) 2008 Elsevier Ltd. All rights reserved.