3-([5-methyl-2-(4-(trifluoromethyl)phenyl)oxazol-4-yl]methoxy)benzaldehyde | 174258-10-7

• 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-([5-methyl-2-(4-(trifluoromethyl)phenyl)oxazol-4-yl]methoxy)benzaldehyde
• 英文别名: 3-[5-methyl-2-(-4-trifluoromethyl-phenyl)-oxazol-4-ylmethoxy)-benzaldehyde；3-[5-Methyl-2-(4-trifluoromethyl-phenyl)-oxazol-4-ylmethoxy]-benzaldehyde；3-[[5-Methyl-2-[4-(trifluoromethyl)phenyl]-1,3-oxazol-4-yl]methoxy]benzaldehyde
• CAS: 174258-10-7
• 化学式: C₁₉H₁₄F₃NO₃
• 分子量: 361.32
• InChiKey: OINXXZCWCXUXHJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  26
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.16
• 拓扑面积：
  52.3
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  3-([5-methyl-2-(4-(trifluoromethyl)phenyl)oxazol-4-yl]methoxy)benzaldehyde 在 potassium tert-butylate 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 为溶剂， 反应 52.0h， 生成 3-[3-[[5-Methyl-2-[4-(trifluoromethyl)phenyl]-1,3-oxazol-4-yl]methoxy]phenyl]prop-2-yn-1-ol
  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：

  对三氟甲基苯甲醛 在 盐酸 、 potassium carbonate 、 三氯氧磷 作用下， 以 氯仿 、 乙酸乙酯 、 N,N-二甲基甲酰胺 为溶剂， 反应 8.0h， 生成 3-([5-methyl-2-(4-(trifluoromethyl)phenyl)oxazol-4-yl]methoxy)benzaldehyde
  参考文献：
  名称：

  偶氮苯氧基羟基脲作为5-脂氧合酶的选择性和口服活性抑制剂。

  摘要：

  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

  DOI：

  10.1021/jm950363n

文献信息

• Azolidinediones as antihyperglycemic agents
  申请人：American Home Products Corporation

  公开号：US05468762A1

  公开（公告）日：1995-11-21

  This invention relates to compounds which have oral antihyperglycemic activity of the formula: ##STR1## wherein: R.sup.1 is C.sub.1 -C.sub.6 alkyl, C.sub.3 -C.sub.8 cycloalkyl, thienyl, furyl, pyridyl, ##STR2## R.sup.2 is hydrogen or C.sub.1 -C.sub.6 alkyl; X os O or S; n is 0, 1, or 2; A is ##STR3## Y is O or S; Z is N or CH when Y is O and Z is CH when Y is S; or a pharmaceutically acceptable salt thereof.

  这项发明涉及具有口服抗高血糖活性的化合物，其化学式为：##STR1## 其中：R.sup.1为C.sub.1 -C.sub.6烷基，C.sub.3 -C.sub.8环烷基，噻吩基，呋喃基，吡啶基，##STR2## R.sup.2为氢或C.sub.1 -C.sub.6烷基；X为O或S；n为0、1或2；A为##STR3## Y为O或S；Z为N或CH，当Y为O时Z为CH，当Y为S时Z为CH；或其药用盐。
• New azolidinediones and thiadiazolidinediones as antihyperglycemic agents
  申请人：American Home Products Corporation

  公开号：US05532256A1

  公开（公告）日：1996-07-02

  This invention relates to novel compounds which have demonstrated oral antihyperglycemic activity in diabetic ob/ob and db/db mice, animal models on non-insulin dependent diabetes mellitus (NIDDM ot Type II diabetes). These compounds have the formula: ##STR1## wherein: R.sup.1 is C.sub.1 -C.sub.6 alkyl, C.sub.3 -C.sub.8 cycloalkyl, thienyl, furyl, pyridyl, ##STR2## where R.sup.10 is hydrogen, C.sub.1 -C.sub.6 alkyl, fluorine, chlorine, bromine, iodine, C.sub.1 -C.sub.6 alkyoxy, trifluoroalkyl or trifluoroalkoxy; R.sup.2 is hydrogen or C.sub.1 -C.sub.6 alkyl; X is O or S; n is 0, 1, or 2; A is ##STR3## where R.sup.3 is hydrogen, C.sub.1 -C.sub.6 alkyl, halogen, C.sub.1 -C.sub.6 alkoxy, trifluoroalkyl or trifluoroalkoxy; B is ##STR4## where R.sup.4 is hydrogen, C.sub.1 -C.sub.6 alkyl, allyl, C.sub.6 -C.sub.10 aryl, C.sub.6 -C.sub.10 aryl-(CH.sub.2).sub.1-6 --, fluorine, chlorine, bromine, iodine, trimethylsilyl or C.sub.3 -C.sub.8 cycloalkyl; R.sup.5 is hydrogen, C.sub.1 -C.sub.6 alkyl, C.sub.6 -C.sub.10 aryl, or C.sub.6 -C.sub.10 aryl-(CH.sub.2).sub.1-6 --; m is 0, 1, or 2; R.sup.6 is hydrogen or C.sub.1 -C.sub.6 alkyl; R.sup.7 is hydrogen or C.sub.1 -C.sub.6 alkyl; R.sup.8 and R.sup.9 are selected independently from hydrogen, C.sub.1 -C.sub.6 alkyl, fluorine, chlorine, bromine, or iodine; Y is S; Z is N or CH; or a pharmaceutically acceptable salt thereof.

  这项发明涉及一种新型化合物，已在糖尿病ob/ob和db/db小鼠中表现出口服抗高血糖活性，这些小鼠是非胰岛素依赖型糖尿病（NIDDM或2型糖尿病）的动物模型。这些化合物的分子式为：其中：R.sup.1为C.sub.1 -C.sub.6烷基，C.sub.3 -C.sub.8环烷基，噻吩基，呋喃基，吡啶基，其中R.sup.10为氢，C.sub.1 -C.sub.6烷基，氟，氯，溴，碘，C.sub.1 -C.sub.6烷氧基，三氟甲基或三氟甲氧基；R.sup.2为氢或C.sub.1 -C.sub.6烷基；X为O或S；n为0, 1或2；A为其中R.sup.3为氢，C.sub.1 -C.sub.6烷基，卤素，C.sub.1 -C.sub.6烷氧基，三氟甲基或三氟甲氧基；B为其中R.sup.4为氢，C.sub.1 -C.sub.6烷基，烯丙基，C.sub.6 -C.sub.10芳基，C.sub.6 -C.sub.10芳基-(CH.sub.2).sub.1-6 --，氟，氯，溴，碘，三甲基硅基或C.sub.3 -C.sub.8环烷基；R.sup.5为氢，C.sub.1 -C.sub.6烷基，C.sub.6 -C.sub.10芳基，或C.sub.6 -C.sub.10芳基-(CH.sub.2).sub.1-6 --；m为0, 1或2；R.sup.6为氢或C.sub.1 -C.sub.6烷基；R.sup.7为氢或C.sub.1 -C.sub.6烷基；R.sup.8和R.sup.9分别选自氢，C.sub.1 -C.sub.6烷基，氟，氯，溴，或碘；Y为S；Z为N或CH；或其药学上可接受的盐。
• Antihyperglycemic activity of new 1,2,4-oxadiazolidine-3,5-diones
  作者：M Malamas

  DOI：10.1016/s0223-5234(00)01191-0

  日期：2001.1

  A series of 1,2,4-oxadiazolidine-3,5-diones was synthesized and evaluated as oral antihyperglycemic agents in the obese insulin resistant db/db and ob/ob mouse - the two models for Type 2 diabetes mellitus. The majority of the prepared methoxy- and ethoxy-linked oxazole 1,2,4-oxadiazolidine-3,5-diones normalized plasma glucose levels at the 100 mg kg(-1) oral dose in the db/db diabetic mouse model, and several amongst them reduced the glucose levels at the 20 mg kg(-1) oral dose. The most potent compounds in the db/db mouse model were also active in the ob/ob mouse model normalizing the plasma glucose levels at the 20 mg kg(-1) oral dose. The trifluoromethoxy analog 32 was the most active compound of the series, reducing significantly the plasma glucose levels at the 5 mg kg(-1) oral dose. Oxadiazole-tailed 1,2,4-oxadiazolidine-3,5-diones were also active in both the db/db and ob/ob diabetic mouse models normalizing plasma glucose levels at the 100 mg kg(-1) oral dose. (C) 2001 Editions scientifiques et medicales Elsevier SAS.
• NEW AZOLIDINEDIONES AS ANTIHYPERGLYCEMIC AGENTS
  申请人：AMERICAN HOME PRODUCTS CORPORATION

  公开号：EP0759919A1

  公开（公告）日：1997-03-05
• AZOLIDINEDIONES AS ANTIHYPERGLYCEMIC AGENTS
  申请人：AMERICAN HOME PRODUCTS CORPORATION

  公开号：EP0759919B1

  公开（公告）日：1998-11-11