4-(chloromethyl)-2-(4-(trifluoromethyl)phenyl)oxazole | 22091-40-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 4-(chloromethyl)-2-(4-(trifluoromethyl)phenyl)oxazole
• 英文别名: 4-(Chloromethyl)-2-[4-(trifluoromethyl)phenyl]-1,3-oxazole
• CAS: 22091-40-3
• 化学式: C₁₁H₇ClF₃NO
• mdl: MFCD11845043
• 分子量: 261.631
• InChiKey: UWXGEXVAIMRWRL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  17
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.181
• 拓扑面积：
  26
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  4-(chloromethyl)-2-(4-(trifluoromethyl)phenyl)oxazole 在 sodium hydride 、 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 59.0h， 生成 (E)-3-{3-[2-(4-Trifluoromethyl-phenyl)-oxazol-4-ylmethoxy]-phenyl}-but-2-enoic acid ethyl ester
  参考文献：
  名称：

  New Azolidinediones as Inhibitors of Protein Tyrosine Phosphatase 1B with Antihyperglycemic Properties

  摘要：

  Insulin resistance in the liver and peripheral tissues together with a pancreatic cell defect are the common causes of type 2 diabetes. It is now appreciated that insulin resistance can result from a defect in the insulin receptor signaling system, at a site post binding of insulin to its receptor. Protein tyrosine phosphatases (PTPases) have been shown to be negative regulators of the insulin receptor. Inhibiton of PTPase may be an effective method in the treatment of type 2 diabetes. A series of azolidinediones has been prepared as protein tyrosine phosphatase 1B (PTP1B) inhibitors. Several compounds were potent inhibitors against the recombinant rat and human PTP1B enzymes with submicromolar IC50 values. Elongated spacers between the azolidinedione moiety and the central aromatic portion of the molecule as well as hydrophobic groups at the vicinity of this aromatic region were very important to the inhibitory activity. Oxadiazolidinediones 87 and 88 and the corresponding acetic acid analogues 119 and 120 were the best h-PTP1B inhibitors with IC50 values in the range of 0.12-0.3 mu M. Several compounds normalized plasma glucose and insulin levels in the ob/ob and db/db diabetic mouse models.

  DOI：

  10.1021/jm990476x
• 作为产物：
  描述：

  methyl 2-(4-trifluoromethylphenyl)oxazole-4-carboxylate 在 lithium aluminium tetrahydride 、 氯化亚砜 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 2.0h， 生成 4-(chloromethyl)-2-(4-(trifluoromethyl)phenyl)oxazole
  参考文献：
  名称：

  Discovery of the disubstituted oxazole analogues as a novel class anti-tuberculotic agents against MDR- and XDR-MTB

  摘要：

  A high-throughput screening effort on 45,000 compounds resulted in the discovery of a disubstituted oxazole as a new structural class inhibitor of Mycobacterium tuberculosis (Mtb). In order to improve the activity and investigate the SAR of this scaffold, a series of disubstituted azole analogues have been designed and synthesized. The newly synthesized compounds 1a-y were evaluated for their in vitro anti-TB activity versus replicating, multi-and extensive drug resistant Mtb strains. All the compounds, except 1o, 1p and 1q, showed potent anti-TB activity with MIC of 1-64 mg/L. The test of broad spectrum panel revealed that this series are specific to Mtb. The cytotoxicity assessment indicated that the compounds were not cytotoxic against HEK 293 cells. The compounds could have a novel mechanism to anti-Mtb as they can inhibit drug sensitive and drug resistant Mtb. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2015.09.072

文献信息

• Design, synthesis, and insecticidal/acaricidal evaluation of novel pyrimidinamine derivatives containing phenyloxazole moiety
  作者：Ning Zhang、Ming-Zhi Huang、Ai-Ping Liu、Min-Hua Liu、Li-Zhong Li、Chun-Ge Zhou、Ye-Guo Ren、Xiao-Ming Ou、Chu-Yun Long、Jiong Sun、Ming-Ming Dang、Zhi-Li Lan

  DOI：10.1007/s11696-019-00932-5

  日期：2020.3

  A series of novel pyrimidinamine derivatives containing phenyloxazole moiety were designed and synthesized, and their structures were characterized by 1H NMR, MS, and elemental analyses. The bioassay results displayed that some compounds exhibited remarkable insecticidal activities against Aphis fabae and Tetranychus cinnabarinus. Especially, 5-chloro-6-ethyl-2-methyl-N-((2-(p-tolyl)oxazol-4-yl)me

  设计并合成了一系列含有苯基恶唑部分的新型嘧啶胺衍生物，并通过1 H NMR，MS和元素分析对其结构进行了表征。生物分析结果表明，某些化合物对蚜虫和朱砂叶螨具有显着的杀虫活性。特别是，5-氯-6-乙基-2-甲基- ñ - （（2-（p -甲苯基）恶唑-4-基）甲基）嘧啶-4-胺（90）显示针对有效的活性A.蚜，优异的与商业杀虫剂吡虫啉相比。另外，5-氯-6-乙基-2-甲基-N-（（（2-（4-（三氟甲基）苯基）恶唑-4-基）甲基）嘧啶-4-胺（9r）显示出对朱砂毛虫的强效活性，其效果不如市售杀虫剂螺旋螺。还讨论了目标化合物的构效关系研究。
• Substituted naphthylenes for the treatment of non-insulin dependent diabetes mellitus
  申请人：Wyeth

  公开号：US20030216442A1

  公开（公告）日：2003-11-20

  This invention provides compounds of formula I, having the structure 1 wherein R 1 , R 4 , A, and Z are as defined in the specification, or a pharmaceutically acceptable salt thereof, that are useful in treating metabolic disorders mediated by insulin resistance or hyperglycemia.

  这项发明提供了具有结构的I式化合物，其结构如下： 其中R 1 ，R 4 ，A和Z如规范中定义，或其药学上可接受的盐，可用于治疗由胰岛素抵抗或高血糖介导的代谢紊乱。
• [EN] HETEROCYCLIC MITOCHONDRIAL ACTIVITY INHIBITORS AND USES THEREOF<br/>[FR] INHIBITEURS HÉTÉROCYCLIQUES DE L'ACTIVITÉ MITOCHONDRIALE ET UTILISATIONS ASSOCIÉES
  申请人：UNIV MONTREAL

  公开号：WO2019084662A1

  公开（公告）日：2019-05-09

  Heterocyclic compounds of Formula (I) and pharmaceutically acceptable salt thereof are disclosed. The use of such heterocyclic compounds and pharmaceutically acceptable salt thereof for the treatment of cancers, and more particularly cancers sensitive to mitochondrial activity inhibition and increased reactive oxygen species (ROS) levels, is also disclosed. Such cancers include acute myeloid leukemia (AML), preferably AML characterized by certain features, such as high level of expression of one or more Homeobox (HOX)-network genes, high and/or low expression of specific genes, the presence of one or more cytogenetic or molecular risk factors such as intermediate cytogenetic risk, Normal Karyotype (A/K), mutated NPM1, mutated CEBPA, mutated FLT3, mutated DNMT3A, mutated TET2, mutated IDH1, mutated IDH2, mutated RUNX1, mutated WT1, mutated SRSF2, intermediate cytogenetic risk with abnormal karyotype (intern(abnK)), trisomy 8 (+8) and/or abnormal chromosome (5/7), and/or a high leukemic stem cell (LSC) frequency.

  化合物的分子式（I）的杂环化合物及其药用盐已被披露。还披露了这种杂环化合物及其药用盐用于治疗癌症，尤其是对于对线粒体活性抑制和增加活性氧化物（ROS）水平敏感的癌症。这些癌症包括急性髓样白血病（AML），最好是具有某些特征的AML，例如高水平表达一个或多个Homeobox（HOX）网络基因，特定基因的高和/或低表达，存在一个或多个细胞遗传学或分子风险因素，如中等细胞遗传学风险，正常核型（A/K），突变NPM1，突变CEBPA，突变FLT3，突变DNMT3A，突变TET2，突变IDH1，突变IDH2，突变RUNX1，突变WT1，突变SRSF2，具有异常核型的中等细胞遗传学风险（intern(abnK)），三体8（+8）和/或异常染色体（5/7），和/或高白血病干细胞（LSC）频率。
• Azole Phenoxy Hydroxyureas as Selective and Orally Active Inhibitors of 5-Lipoxygenase
  作者：Michael S. Malamas、Richard P. Carlson、David Grimes、Ralph Howell、Keith Glaser、Iwan Gunawan、James A. Nelson、Mira Kanzelberger、Uresh Shah、David A. Hartman

  DOI：10.1021/jm950363n

  日期：1996.1.1

  demonstrated high and selective 5-LO inhibitory activity in the in vitro assays, with IC50 values ranging from 0.08 microM in mouse macrophages to 0.8 microM in human peripheral monocytes to 1.2 microM in human whole blood. This activity was selective for 5-LO, as concentrations up to 15 microM in mouse macrophages did not affect prostaglandin formation. Oxazole 59 was the most active inhibitor in the human

  唑类苯氧基羟基脲是一类新的5-脂氧合酶（5-LO）抑制剂。结构-活性关系研究表明，恶唑尾巴的2-苯基部分的负电取代基增加了这些抑制剂的离体效能。噻唑类似物上的类似取代对离体活性仅有很小的贡献。三氟甲基取代的恶唑24是离体（6 h预处理大鼠）和体内（3 h预处理大鼠）RPAR测定中最佳恶唑系列化合物，ED50值分别约为1和3.6 mg / kg，但在过敏性豚鼠试验中的活性较弱。恶唑50在RPAR和豚鼠体内模型中均具有同等活性，与齐留通相似。未取代的噻唑52是噻唑系列中最好的化合物，在口服剂量为10 mg / kg的情况下，通过抑制RPAR分析（预处理3小时的大鼠）中白三烯B4的生物合成为99％，而在静脉注射剂量为10 mg / kg的情况下，对变应性豚鼠的支气管收缩作用抑制了50％公斤。在体外测定中，恶唑24表现出高选择性的5-LO抑制活性，IC50值范围从小鼠巨噬细胞中的0.08 microM到人外周单核细胞中的0
• Design, Synthesis and Biological Evaluation of <i>N</i>-((2-phenyloxazol-4-yl)methyl) Pyrimidine Carboxamide Derivatives as Potential Fungicidal Agents
  作者：Danling Huang、Shumin Zheng、Yong-Xian Cheng

  DOI：10.1515/hc-2020-0117

  日期：2020.1.31

  derivatives were designed, synthesized, and characterized by 1H NMR, 13C NMR, and HRMS. The fungicidal activities of these new compounds against Sclerotinia sclerotiorum, Botrytis cinereal, and Colletotrichum fragariae were evaluated. The results indicated that compounds 5b, 5f, and 5g displayed potential fungicidal activities against tested fungi, especially 5f exhibited IC50 value of 28.9 mg/L against

  设计、合成了 12 种 N-((2-phenyloxazol-4-yl)methyl) 嘧啶甲酰胺衍生物，并通过以下方法表征1核磁共振氢谱，13C 核磁共振和 HRMS。这些新化合物的杀菌活性菌核病菌,​​ Botrytis cinereal， 和草莓炭疽病菌进行了评估。结果表明，化合物 5b、5f 和 5g 对受试真菌具有潜在的杀菌活性，特别是 5f 表现出 IC50值 28.9 毫克/升对核盘菌. 此外，化合物 5f 和 5g 显示出 IC5054.8 毫克/升和 62.2 毫克/升对C. fragariae分别表明它们比商业杀菌剂恶霉灵更有效。讨论了表面的构效关系，可能有利于杀菌剂的开发和新型杀菌剂的发现。