14-methyl-5,7,8,13,13b,14-hexahydroindolo[2',3':3,4]pyrido[2,1-b]quinazoline | 1394329-02-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: 14-methyl-5,7,8,13,13b,14-hexahydroindolo[2',3':3,4]pyrido[2,1-b]quinazoline
• 英文别名: 5 - methyleneevodiamine；14-methyl-5,7,8,13,13b,14-hexahydroindolo[2′,3′:3,4]-pyrido[2,1-b]quinazoline；5-hydroevodiamine；5-deoxoevodiamine；5-(Methylene)Evodiamine；21-methyl-3,13,21-triazapentacyclo[11.8.0.02,10.04,9.015,20]henicosa-2(10),4,6,8,15,17,19-heptaene
• CAS: 1394329-02-2
• 化学式: C₁₉H₁₉N₃
• 分子量: 289.38
• InChiKey: NRPJNCRKRUUPEY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  22
• 可旋转键数：
  0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  22.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  14-methyl-5,7,8,13,13b,14-hexahydroindolo[2',3':3,4]pyrido[2,1-b]quinazoline 、 4-氯苯甲酰氯 在 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 12.5h， 以56.9%的产率得到(4-Chlorophenyl)-(21-methyl-3,13,21-triazapentacyclo[11.8.0.02,10.04,9.015,20]henicosa-2(10),4,6,8,15,17,19-heptaen-3-yl)methanone
  参考文献：
  名称：

  New Tricks for an Old Natural Product: Discovery of Highly Potent Evodiamine Derivatives as Novel Antitumor Agents by Systemic Structure–Activity Relationship Analysis and Biological Evaluations

  摘要：

  Evodiamine is a quinazolinocarboline alkaloid isolated from the fruits of traditional Chinese herb Evodiae fructus. Previously, we identified N13-substituted evodiamine derivatives as potent topoisomerase I inhibitors by structure-based virtual screening and lead optimization. Herein, a library of novel evodiamine derivatives bearing various substitutions or modified scaffold were synthesized. Among them, a number of evodiamine derivatives showed substantial increase of the antitumor activity, with GI(50) values lower than 3 nM. Moreover, these highly potent compounds can effectively induce the apoptosis of A549 cells. Interestingly, further computational target prediction calculations in combination with biological assays confirmed that the evodiamine derivatives acted by dual inhibition of topoisomerases I and II. Moreover, several hydroxyl derivatives, such as 10-hydroxyl evodiamine (10j) and 3-amino-10-hydroxyl evodiamine (18g), also showed good in vivo antitumor efficacy and low toxicity at the dose of 1 mg/kg or 2 mg/kg. They represent promising candidates for the development of novel antitumor agents.

  DOI：

  10.1021/jm300605m
• 作为产物：
  描述：

  吴茱萸碱 在 苯硅烷 、 四乙基溴化铵 作用下， 以 乙腈 为溶剂， 以32%的产率得到14-methyl-5,7,8,13,13b,14-hexahydroindolo[2',3':3,4]pyrido[2,1-b]quinazoline
  参考文献：
  名称：

  氢硅烷介导的酰胺电化学还原

  摘要：

  通过使用不含任何有毒或昂贵金属的氢硅烷实现了酰胺的电化学还原。关键的反应性酮基自由基中间体是通过阴极还原生成的。与阳极产生的甲硅烷基自由基或溴化锌的连续反应导致化学选择性脱氧，得到相应的胺。

  DOI：

  10.1021/acs.joc.1c00931

文献信息

• 一类吴茱萸碱类化合物及其制备方法与应用
  申请人：中山大学

  公开号：CN107141288B

  公开（公告）日：2019-12-27

  本发明公开了一类吴茱萸碱类化合物及其制备方法与应用。所述吴茱萸碱类化合物具有通式（I）的结构，包括其消旋体、d‑型或l‑型异构体，及其药学上可接受的盐。这类吴茱萸碱类化合物经药理试验证明具有明显的磷酸二酯酶PDE5抑制活性，部分化合物对PDE5的抑制活性与西地那非相当，且对磷酸二酯酶PDE6具有更强的选择性。该类化合物在临床上可以用来改善或治疗心脑血管系统、泌尿系统症状或疾病，尤其可以用来改善或治疗包括勃起功能障碍及肺动脉高压在内的症状或疾病。。
• Design, synthesis and biological evaluation of novel evodiamine and rutaecarpine derivatives against phytopathogenic fungi
  作者：Cheng-Jie Yang、Hai-xin Li、Jing-Ru Wang、Zhi-Jun Zhang、Tian-Lin Wu、Ying-Qian Liu、Chen Tang、Qing-Ru Chu、Sha-Sha Du、Ying-Hui He

  DOI：10.1016/j.ejmech.2021.113937

  日期：2022.1

  medicine Evodia rutaecarpa, which have been reported to have various biological activities in past decades. To explore the potential applications for evodiamine and rutaecarpine alkaloids and their derivatives, various kinds of evodiamine and rutaecarpine derivatives were designed and synthesized. Their antifungal profile against six phytopathogenic fungi Rhizoctonia solani, Botrytis cinerea, Fusarium

  吴茱萸碱和吴茱萸碱是从传统中草药吴茱萸中分离得到的两种生物碱，在过去的几十年中被报道具有多种生物活性。为探索吴茱萸碱生物碱及其衍生物的潜在应用，设计合成了多种吴茱萸碱衍生物。它们对六种植物病原真菌立枯丝核菌、灰霉病菌、禾谷镰刀菌、尖孢镰刀菌、核盘菌和稻瘟病菌的抗真菌谱第一次被评估。此外，合成了一系列rutaecarpine的修饰咪唑衍生物，以研究构效关系。体外抗真菌活性结果表明，芸香芸香碱A1咪唑衍生物对R. solani、B. cinerea、F. oxysporum、S. sclerotiorum、M. oryzae和F. graminearum具有广谱抑制活性，EC 50值分别为 1.97、5.97、12.72、2.87 和 16.58 μg/mL。初步机理研究表明，化合物A1可能引起核盘菌菌丝体异常，线粒体变形和肿胀，抑制菌核形成和萌发。此外，化合物A1在400、200、100、50
• Identification of a neuroprotective and selective butyrylcholinesterase inhibitor derived from the natural alkaloid evodiamine
  作者：Guozheng Huang、Beata Kling、Fouad H. Darras、Jörg Heilmann、Michael Decker

  DOI：10.1016/j.ejmech.2014.05.002

  日期：2014.6

  Two sets of carbamates based on the natural alkaloid evodiamine were designed, synthesized and evaluated as potential butyrylcholinesterase inhibitors. Although a set of carbamates of 3-hydroxyevodiamine (10a-f) is inactive both at AChE and BChE, carbamates of 5-deoxo-3-hydroxyevodiamine (11a-f) exhibit much better potency with selectivity toward BChE. The heptyl carbamate of 5-deoxo-3-hydroxyevodiamine (11c) shows the best potency with an IC50 value of 77 nM and very good selectivity over AChE. ORAC and cell-based assays indicate 11c owns pronounced antioxidant properties with 1.75 Trolox equivalents and strong neuroprotection even from 1 mu M onwards. These combined activities might enable compound 11c to be a potential candidate for treatment of Alzheimer's disease. (C) 2014 Elsevier Masson SAS. All rights reserved.
• ANTI-CANCER PHARMACEUTICAL COMPOSITION FOR TARGETING HEAT SHOCK PROTEIN 70, CONTAINING INDOLOQUINAZOLIDINE ALKALOID
  申请人：SEOUL NATIONAL UNIVERSITY R & DB FOUNDATION

  公开号：US20240140949A1

  公开（公告）日：2024-05-02

  The present invention relates to: an anti-cancer pharmaceutical composition for targeting heat shock protein 70, containing an indoloquinazolidine alkaloid; and the like. The indoloquinazolidine alkaloid of the present invention inhibits the growth of tumors and inhibits the expression of HSP70 protein and the colony formation activity of cancer cells, and inhibits the growth of tumors in mouse models with xenografts of a cancer cell line and xenografts of patient-derived cancer, and inhibits the growth of cancer cells resistant to drugs such as pemetrexed, cisplatin, and paclitaxel, and thus is expected to be widely usable in the prevention and treatment of various types of cancer.
• Hydrosilane-Mediated Electrochemical Reduction of Amides
  作者：Kazuhiro Okamoto、Shingo Nagahara、Yasushi Imada、Risako Narita、Yoshikazu Kitano、Kazuhiro Chiba

  DOI：10.1021/acs.joc.1c00931

  日期：2021.11.19

  Electrochemical reduction of amides was achieved by using a hydrosilane without any toxic or expensive metals. The key reactive ketyl radical intermediate was generated by cathodic reduction. Continuous reaction with anodically generated silyl radicals or zinc bromide resulted in chemoselective deoxygenation to give the corresponding amines.

  通过使用不含任何有毒或昂贵金属的氢硅烷实现了酰胺的电化学还原。关键的反应性酮基自由基中间体是通过阴极还原生成的。与阳极产生的甲硅烷基自由基或溴化锌的连续反应导致化学选择性脱氧，得到相应的胺。