2,5-二甲氧基-4-甲基苯胺 | 34238-59-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 2,5-二甲氧基-4-甲基苯胺
• 英文名称: 4-methyl-2,5-dimethoxyaniline
• 英文别名: 2,5-Dimethoxy-4-methylaniline
• CAS: 34238-59-0
• 化学式: C₉H₁₃NO₂
• 分子量: 167.208
• InChiKey: CWIBPAGDXLMLNI-UHFFFAOYSA-N

物化性质

• 熔点：
  112-113 °C(Solv: water (7732-18-5); ethanol (64-17-5))
• 沸点：
  287.1±35.0 °C(Predicted)
• 密度：
  1.071±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  12
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  44.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2,5-二甲氧基-4-甲基苯胺 在 三氯氧磷 作用下， 以 苯 为溶剂， 反应 2.0h， 生成 (Z) N-(4'methyl-2',5'-dimethoxyphenyl)formamidine
  参考文献：
  名称：

  New findings on the Vilsmeier-Haack approach to quinoline derivatives

  摘要：

  The presence of electron-releasing substituents on the aromatic ring of anilides. although necessary for the Vilsmeier-Haack cyclization to quinolines to proceed efficiently, can cause failure of the expected cyclization. leading to (Z) N,N-dimethylformamidines through an alternative course. A similar behaviour is observed when pi-donor groups are introduced on the alpha position of the anilide, although in this case some cyclization to quinoline derivatives generally occurs.

  DOI：

  10.1016/s0040-4020(01)80253-2
• 作为产物：
  描述：

  甲基氢醌 在 盐酸 、 sodium hydroxide 、 4-偶氮基苯磺酸酯 、 potassium carbonate 、 溶剂黄146 、 丙酮 作用下， 生成 2,5-二甲氧基-4-甲基苯胺
  参考文献：
  名称：

  Mamalis et al., Journal of the Chemical Society, 1959, p. 3350,3356

  摘要：

  DOI：

文献信息

• Synthesis and evaluation of phenyl- and benzoylpiperazines as potential serotonergic agents
  作者：Robert A. Lyon、Milt Titeler、J. D. McKenney、Philip S. Magee、Richard A. Glennon

  DOI：10.1021/jm00155a008

  日期：1986.5

  The binding of a series of phenylpiperazines (3) and benzoylpiperazines (4) to central serotonin (5-HT) sites was investigated. Several derivatives of 3 displayed nanomolar affinities for 5-HT1 sites, whereas derivatives of 4 were essentially inactive both at 5-HT1 and 5-HT2 sites. 1-(2-Methoxyphenyl)piperazine (2-MPP, 3a) was found to possess an affinity (Ki = 35 nM) for 5-HT1 sites comparable to

  研究了一系列苯基哌嗪（3）和苯甲酰基哌嗪（4）与5-羟色胺中心部位的结合。3的几种衍生物显示出对5-HT1位点的纳摩尔亲和力，而4的衍生物在5-HT1和5-HT2位点上基本上没有活性。发现1-（2-甲氧基苯基）哌嗪（2-MPP，3a）对5-HT1位点具有亲和力（Ki = 35 nM）与公认的5-HT激动剂1- [3-（三氟甲基）苯基]哌嗪（TFMPP）（Ki = 20 nM）；图3a还显示了对5-HT1位点的100倍选择性（相比于TFMPP的8倍）。在使用训练以从盐水中区分TFMPP（ED50 = 0.17 mg / kg）的大鼠进行的刺激泛化测试中，发现3a与训练药物几乎等效（ED50 = 0.22 mg / kg）。
• A Novel Redox Modulator Induces a GPX4-Mediated Cell Death That Is Dependent on Iron and Reactive Oxygen Species
  作者：Shuai Hu、Mario Sechi、Pankaj Kumar Singh、Lipeng Dai、Sean McCann、Duxin Sun、Mats Ljungman、Nouri Neamati

  DOI：10.1021/acs.jmedchem.0c01016

  日期：2020.9.10

  modulators have been developed as an attractive approach to treat cancer. Herein, we report the synthesis, identification, and biological evaluation of a quinazolinedione reactive oxygen species (ROS) inducer, QD394, with significant cytotoxicity in pancreatic cancer cells. QD394 shows a transcriptomic profile remarkably similar to napabucasin, a cancer stemness inhibitor. Both small molecules inhibit

  氧化还原调节剂已被开发为治疗癌症的有吸引力的方法。在此，我们报告了喹唑啉二酮活性氧 (ROS) 诱导剂 QD394 的合成、鉴定和生物学评估，该诱导剂在胰腺癌细胞中具有显着的细胞毒性。QD394 显示出与癌症干性抑制剂 napabucasin 非常相似的转录组学特征。这两种小分子都抑制 STAT3 磷酸化，增加细胞 ROS，并降低 GSH/GSSG 比率。此外，QD394 导致铁和 ROS 依赖性、GPX4 介导的细胞死亡，表明铁死亡是主要机制。重要的是，QD394 降低了 LRPPRC 和 PNPT1 的表达，这两种蛋白质参与线粒体 RNA 分解代谢过程，并且都与胰腺癌患者的总生存期呈负相关。药代动力学指导的先导优化产生了衍生物 QD394-Me，与 QD394 相比，它在小鼠中显示出改善的血浆稳定性和降低的毒性。总体而言，QD394 和 QD394-Me 代表了新型 ROS 诱导药物样化合物，值得进一步开发用于治疗胰腺癌。
• PYRIMIDINE DERIVATIVES AS ZAP-70 INHIBITORS
  申请人：Ramsden Nigel

  公开号：US20120142667A1

  公开（公告）日：2012-06-07

  The invention relates to compounds of formula (I) wherein R 1 to R 5 , X and X 1 to X 3 have the meaning as cited in the description and the claims. Said compounds are useful as inhibitors of ZAP-70 for the treatment or prophylaxis of immunological, inflammatory, autoimmune, allergic disorders, and immunologically-mediated diseases. The invention also relates to pharmaceutical compositions including said compounds, the preparation of such compounds as well as the use as medicaments.

  本发明涉及式（I）的化合物，其中R1至R5、X和X1至X3的含义如描述和权利要求中所述。所述化合物可用作ZAP-70的抑制剂，用于治疗或预防免疫、炎症、自身免疫、过敏性疾病和免疫介导的疾病。本发明还涉及包括上述化合物的制药组合物，以及作为药物的用途和制备这种化合物的方法。
• Dérivés de glycinamide comme agonistes des récepteurs de la cholecystokinine
  申请人：SANOFI

  公开号：EP0697403A1

  公开（公告）日：1996-02-21

  La présente invention concerne des composés de formule : qui sont des agonistes des récepteurs de la cholecystokinine et compositions pharmaceutiques les contenant.

  本发明涉及作为胆囊收缩素受体激动剂的式 ： 是胆囊收缩素受体激动剂，本发明涉及含有它们的药物组合物。
• 2-(Quinazolin-4-ylamino)-[1,4]benzoquinones as Covalent-Binding, Irreversible Inhibitors of the Kinase Domain of Vascular Endothelial Growth Factor Receptor-2
  作者：Allan Wissner、M. Brawner Floyd、Bernard D. Johnson、Heidi Fraser、Charles Ingalls、Thomas Nittoli、Russell G. Dushin、Carolyn Discafani、Ramaswamy Nilakantan、Joseph Marini、Malini Ravi、Kinwang Cheung、Xingzhi Tan、Sylvia Musto、Tami Annable、Marshall M. Siegel、Frank Loganzo

  DOI：10.1021/jm050559f

  日期：2005.12.1

  A series of 2-(quinazolin-4-ylamino)-[1,4] benzoquinone derivatives that function as potent covalent-binding, irreversible inhibitors of the kinase domain of vascular endothelial growth factor receptor-2 (VEGFR-2) has been prepared by ceric ammonium nitrate oxidation of substituted (2,5-dimethoxyphenyl)(6,7-disubstituted-quinazolin-4-yl)amines and by displacement of the chlorine atom of substituted 2-chloro-5-(6,7-disubstituted-quinazolin-4-ylamino)-[1,41benzoquinones with various amines, anilines, phenols, and alcohols. Enzyme studies were conducted in the absence and presence of glutathione and plasma. Several of the compounds inhibit VEGF-stimulated autophosphorylation in intact cells. Kinetic experiments were performed to study the reactivity of selected inhibitors toward glutathione. Reactivities correlated with LUMO energies calculated as averages of those of individual conformers weighted by the Boltzmann distribution. These results and molecular modeling were used to rationalize the biological observations. The compounds behave as non-ATP-competitive inhibitors. Unequivocal evidence, from mass spectral studies, indicates that these inhibitors form a covalent interaction with Cys-1045. One member of this series displays antitumor activity in an in vivo model.

表征谱图