3,6-bis(4-methoxyphenyl)-7H-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazine

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 3,6-bis(4-methoxyphenyl)-7H-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazine
• 英文别名: 3-(4-methoxyphenyl)-6-(4-methoxyphenyl)-7H-[1,2,4]-triazolo-[3,4-b]-[1,3,4]-thiadiazine；3-(4-methoxyphenyl)-6-(4-methoxyphenyl)-7H-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazine
• 化学式: C₁₈H₁₆N₄O₂S
• mdl: MFCD03460362
• 分子量: 352.417
• InChiKey: NCMKRJBGQAIBBB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  25
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  86.8
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  1-(4-methoxybenzoyl)-imidazole 在 一水合肼 、 potassium hydroxide 作用下， 以 乙醇 为溶剂， 反应 15.5h， 生成 3,6-bis(4-methoxyphenyl)-7H-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazine
  参考文献：
  名称：

  Preliminary SAR and biological evaluation of antitubercular triazolothiadiazine derivatives against drug-susceptible and drug-resistant Mtb strains

  摘要：

  Following up the SAR study of triazolothiadiazoles for their antitubercular activities targeting Mt SD in our previous study, on the principle of scaffold hopping, the C3 and C6 positions of triazolothiadiazine were examined systematically to define a preliminary structure-activity relationship (SAR) with respect to biological activity. This study herein highlights the potential of two highly potent advanced leads 6c-3, 6g-3 and several other compounds with comparable potencies as promising new candidates for the treatment of TB (6c-3, MIC-H37Rv = 0.25 mu g/mL; MIC-MDRTB = 2.0 mu g/mL; MIC-RDRTB = 0.25 mu g/mL; Mt SD-IC50 = 86.39 mu g/mL; and 6g-3, MIC-H37Rv = 1.0 mu g/mL; MIC-MDRTB = 4.0 mu g/mL; MICRDRTB = 2.0 mu g/mL; Mt SD-IC50 = 73.57 mu g/mL). Compounds 6c-3 and 6g-3 possessed a para-nitro phenyl at the 6 position showed low Vero and HepG2 cells toxicity, turning out to be two excellent lead candidates for preclinical trials. In addition, in vitro Mt SD inhibitory assay indicates that Mt SD is at least one of the targets for their antitubercular activity. Thus, they may turn out to be promising multidrug-resistance- reversing agents. (C) 2016 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2016.10.027

文献信息

• Potential Broad Spectrum Anthelmintics IV: Design, Synthesis, and Antiparasitic Screening of Certain 3,6-Disubstituted- (7H) -s -triazolo- [3,4-b][1,3,4]thiadiazine Derivatives
  作者：M.A. El-Dawy、A.-Mohsen M.E. Omar、Abla M. Ismail、A.A.B. Hazzaa

  DOI：10.1002/jps.2600720111

  日期：1983.1

  Abstract A series of 3,6-disubstituted-(7H)-s-triazolo[3,4-b][l,3,4]- thiadiazine derivatives were prepared. The compounds were designed to obtain structural similarities and/or bear isosteric relation with certain fused systems encountered in some well-known antiparasitic drugs. The substituents in all products were selected according to the Topliss scheme. Preliminary screening for antiparasitic

  摘要制备了一系列3,6-二取代-（7H）-s-三唑并[3,4-b] [1,3,4]-噻二嗪衍生物。设计这些化合物以获得与某些众所周知的抗寄生虫药物中遇到的某些融合系统的结构相似性和/或具有等位关系。根据Topliss方案选择所有产物中的取代基。使用A虫（Ascaris vitulorum）初步筛选抗寄生虫活性表明，6取代的衍生物通常比3取代的衍生物更具活性，并且π效应比σ效应更为明显。
• Exploration of a library of triazolothiadiazole and triazolothiadiazine compounds as a highly potent and selective family of cholinesterase and monoamine oxidase inhibitors: design, synthesis, X-ray diffraction analysis and molecular docking studies
  作者：Imtiaz Khan、Syeda Mahwish Bakht、Aliya Ibrar、Saba Abbas、Shahid Hameed、Jonathan M. White、Usman Ali Rana、Sumera Zaib、Mohammad Shahid、Jamshed Iqbal

  DOI：10.1039/c5ra00906e

  日期：——

  There is a high demand for the collection of small organic molecules (especially N-heterocycles) with diversity and complexity in the process of drug discovery.

  在药物发现过程中，对收集具有多样性和复杂性的小有机分子（特别是N-杂环化合物）有很高的需求。
• Identification of a potent new chemotype for the selective inhibition of PDE4
  作者：Amanda P. Skoumbourdis、Ruili Huang、Noel Southall、William Leister、Vicky Guo、Ming-Hsuang Cho、James Inglese、Marshall Nirenberg、Christopher P. Austin、Menghang Xia、Craig J. Thomas

  DOI：10.1016/j.bmcl.2008.01.028

  日期：2008.2

  A series of substituted 3,6-diphenyl-7H-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazines were prepared and analyzed as inhibitors of phosphodiesterase 4 (PDE4). Synthesis, structure-activity relationships, and the selectivity of a highly potent analogue against related phosphodiesterase isoforms are presented.

  制备并分析了一系列取代的 3,6-二苯基-7H-[1,2,4] 三唑并 [3,4-b][1,3,4] 噻二嗪作为磷酸二酯酶 4 (PDE4) 的抑制剂。介绍了合成、构效关系以及针对相关磷酸二酯酶同种型的高效类似物的选择性。
• 3-Aryl-6-aryl-7H-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazines and analogs as activators of caspases and inducers of apoptosis and the use thereof
  申请人：Cai Xiong Sui

  公开号：US20080045514A1

  公开（公告）日：2008-02-21

  Disclosed are 3-aryl-6-aryl-7H-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazines and analogs thereof, represented by the Formula I: wherein Ar 1 , Q 2 , R 1 , R 2 , dashed line and X are defined herein. The present invention relates to the discovery that compounds having Formula I are activators of caspases and inducers of apoptosis. Therefore, the activators of caspases and inducers of apoptosis of this invention may be used to induce cell death in a variety of clinical conditions in which uncontrolled growth and spread of abnormal cells occurs.

  本发明涉及一种由公式I表示的3-芳基-6-芳基-7H-[1,2,4]三唑并[3,4-b][1,3,4]噻二嗪及其类似物，其中Ar1，Q2，R1，R2，虚线和X的定义如下。本发明发现具有公式I的化合物是caspases的激活剂和凋亡诱导剂。因此，本发明的caspases激活剂和凋亡诱导剂可用于诱导在各种临床病况中出现的异常细胞的无控制增长和扩散的细胞死亡。
• Ibrar, Aliya; Nawazish, Shamyla; Khan, Imtiaz, Acta poloniae pharmaceutica, 2017, vol. 74, # 5, p. 1405 - 1411
  作者：Ibrar, Aliya、Nawazish, Shamyla、Khan, Imtiaz、Noor, Tayyaba、Uzair, Bushra、Bukhari, Syed Majid、Khan, Farhan A.、Zaidi, Asma

  DOI：——

  日期：——