1-(3,4-dimethoxyphenyl)-1H-1,2,3-triazole-4-carboxylic acid

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 1-(3,4-dimethoxyphenyl)-1H-1,2,3-triazole-4-carboxylic acid
• 英文别名: 1-(3,4-dimethoxyphenyl)triazole-4-carboxylic acid
• 化学式: C₁₁H₁₁N₃O₄
• mdl: MFCD19269334
• 分子量: 249.226
• InChiKey: IPQYYIKJFQEKNN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  18
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  86.5
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  冬凌草甲素 、 1-(3,4-dimethoxyphenyl)-1H-1,2,3-triazole-4-carboxylic acid 在 4-二甲氨基吡啶 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 二氯甲烷 为溶剂， 以75%的产率得到(1S,4aR,5S,6S,6aR,9S,11aS)-1,5,6-trihydroxy-4,4-dimethyl-8-methylene-7-oxododecahydro-1H-6,11b-(epoxymethano)-6a,9-methanocyclohepta[a]naphthalen-14-yl 1-(3,4-dimethoxyphenyl)-1H-1,2,3-triazole-4-carboxylate
  参考文献：
  名称：

  Synthesis, and evaluation of in vitro and in vivo anticancer activity of 14-substituted oridonin analogs: A novel and potent cell cycle arrest and apoptosis inducer through the p53-MDM2 pathway

  摘要：

  A series of novel oridonin derivatives bearing various substituents on the 14-OH position were designed and synthesised. Their antitumour activity was evaluated in vitro against three human cancer cell lines (HCT116, BEL7402, and MCF7). Most tested derivatives showed improved anti-proliferative activity compared to the lead compound oridonin and the positive control drug 5-fluorouracil (5-Fu). Among them, compound C7 (IC50 = 0.16 mu M) exhibited the most potent anti-proliferative activity against HCT116 cells; it was about 43- and 155-fold more efficacious than that of oridonin (IC50 = 6.84 mu M) and 5-Fu (IC50 = 24.80 mu M) in HCT116 cancer cells. Interestingly, the IC50 value of compound C7 in L02 normal cells was 23.6-fold higher than that in HCT116 cells; it exhibited better selective anti-proliferative activity and specificity than oridonin and 5-Fu. Furthermore, compound C7 possibly induced cell cycle arrest and apoptosis by regulating the p53-MDM2 signalling pathway. Notably, C7 displayed more significant suppression of tumour growth than oridonin in colon tumour xenograft models where the tumour growth inhibition rate was 85.82%. Therefore, compound C7 could be a potential lead compound for the development of a novel antitumour agent. (C) 2019 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2019.04.005
• 作为产物：
  描述：

  4-叠氮基-1,2-二甲氧基苯 在 copper(ll) sulfate pentahydrate 、 lithium hydroxide monohydrate 、 维生素 C 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 4.0h， 生成 1-(3,4-dimethoxyphenyl)-1H-1,2,3-triazole-4-carboxylic acid
  参考文献：
  名称：

  作为阿尔茨海默病多靶点定向配体的氟化三唑的设计、合成和体外评价

  摘要：

  阿尔茨海默病是多因素的，炎症在疾病进展和严重程度中起主要作用。金属和活性氧 (ROS) 是阿尔茨海默病相关炎症的关键介质。由于多因素性质，开发新药的主要挑战是分子穿越血脑屏障 (BBB) 的能力。我们设计并合成了多靶点定向的含三唑的六氟甲醇，以抑制淀粉样蛋白 β 聚集，同时螯合细胞外空间中存在的过量金属并清除 ROS，从而减轻炎症状况。从筛选的化合物库中，发现化合物1c有效且安全。它已证明抑制淀粉样蛋白 β 聚集 (IC 504.6 μM）通过在成核位点与淀粉样蛋白 β 选择性结合（从分子对接中得到证明）。它还螯合金属（Cu +2、Zn +2和Fe +3）并显着清除ROS。由于分子中存在六氟甲醇部分，它可能有助于渗透 BBB 并改善药代动力学特性。在体外化合物的结果1C指示用于六氟甲醇的含发展滥交三唑酰胺骨架作为针对阿尔茨海默病的多目标导向治疗。

  DOI：

  10.1016/j.bmcl.2021.127999

文献信息

• 4 β -amidotriazole linked podophyllotoxin congeners: DNA topoisomerase-IIα inhibition and potential anticancer agents for prostate cancer
  作者：V. Ganga Reddy、Srinivasa Reddy Bonam、T. Srinivasa Reddy、Ravikumar Akunuri、V.G.M. Naidu、V. Lakshma Nayak、Suresh K. Bhargava、H.M. Sampath Kumar、P. Srihari、Ahmed Kamal

  DOI：10.1016/j.ejmech.2017.12.050

  日期：2018.1

  and topo-II) have occupied a significant role in DNA replication, transcription, and are a promising set of antitumor targets. In the present approach, a series of new 4β-amidotriazole linked podophyllotoxin derivatives (10a-i and 11a-k) were designed, synthesized by employing the click chemistry and their biological activities were evaluated. The majority of derivatives showed promising antiproliferative

  拓扑异构酶（topo-I和topo-II）在DNA复制，转录中起着重要作用，并且是一组有希望的抗肿瘤靶标。在本方法中，一系列新的4个β -amidotriazole联鬼臼毒素衍生物（10A-I和图11A-K ）被设计，通过采用点击化学和它们的生物活性进行了评价合成。大多数衍生物在六种人类癌细胞系上显示出令人鼓舞的抗增殖活性，IC 50值范围为1至10μM。宫颈（HeLa），乳腺（MCF-7），前列腺（DU-145），肺（A549），肝（HepG2）和结肠（HT-29）。其中一些同类物10b，10g和10i已显示出显着的细胞毒性，对测试的癌细胞系的IC 50值<1μM，并且比依托泊苷具有更高的活性。拓扑异构酶介导的DNA弛豫试验结果表明，该衍生物能有效抑制拓扑异构酶II的活性。此外，对DU-145细胞的流式细胞仪分析表明，这些化合物可阻止细胞周期的G2 / M期。还对这些DU-145细胞进行
• 4β-amidotriazole linked podophyllotoxin derivatives as potential anticancer agents
  申请人：COUNCIL OF SCIENTIFIC & INDUSTRIAL RESEARCH

  公开号：US10947248B2

  公开（公告）日：2021-03-16

  The present invention relates to a compound of general formula (A). The invention provides asynthesis of new 4β-amidotriazole linked podophyllotoxin derivatives of general formulae 8a-z to 9a-z useful as potential anticancer agents against human cancer cell lines and process for the preparation thereof. Wherein n=0, 1 and R1-R5═[H, CI, F, CH3, OCH3, 3,4(-OCH2O—), CF3, OCF3, m-OC6H5, OH]

  本发明涉及通式(A)的化合物。本发明提供了通式8a-z至9a-z的新的4β-氨基三唑连接的荚叶肿毒素衍生物的合成及其制备过程，该衍生物可作为潜在的抗癌剂用于人类癌细胞系。其中 n=0、1 和 R1-R5═[H、CI、F、CH3、OCH3、3,4(-OCH2O-)、CF3、OCF3、m-OC6H5、OH]。
• EP3426661A1
  申请人：——

  公开号：EP3426661A1

  公开（公告）日：2019-01-16
• 4BETA-AMIDOTRIAZOLE LINKED PODOPHYLLOTOXIN DERIVATIVES AS POTENTIAL ANTICANCER AGENTS
  申请人：Council of Scientific & Industrial Research

  公开号：EP3426661B1

  公开（公告）日：2021-10-27
• 4Beta-Amidotriazole Linked Podophyllotoxin Derivatives as Potential Anticancer Agents
  申请人：COUNCIL OF SCIENTIFIC & INDUSTRIAL RESEARCH

  公开号：US20200123171A1

  公开（公告）日：2020-04-23

  The present invention relates to a compound of general formula (A). The invention provides asynthesis of new 4β-amidotriazole linked podophyllotoxin derivatives of general formulae 8a-z to 9a-z useful as potential anticancer agents against human cancer cell lines and process for the preparation thereof. Wherein n=0, 1 and R 1 -R 5 ═[H, CI, F, CH 3 , OCH 3 , 3,4(-OCH 2 O—), CF 3 , OCF 3 , m-OC 6 H 5 , OH]