3-[5-(4-trifluoromethoxy-phenyl)-[1,2,4]-oxadiazol-3-ylmethoxy]-benzaldehyde | 166179-23-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 3-[5-(4-trifluoromethoxy-phenyl)-[1,2,4]-oxadiazol-3-ylmethoxy]-benzaldehyde
• 英文别名: 3-[[5-[4-(Trifluoromethoxy)phenyl]-1,2,4-oxadiazol-3-yl]methoxy]benzaldehyde
• CAS: 166179-23-3
• 化学式: C₁₇H₁₁F₃N₂O₄
• 分子量: 364.281
• InChiKey: HAWMIQNOXPMKCM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  26
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  74.4
• 氢给体数：
  0
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  3-[5-(4-trifluoromethoxy-phenyl)-[1,2,4]-oxadiazol-3-ylmethoxy]-benzaldehyde 在 盐酸羟胺 、 sodium acetate 作用下， 以 乙醇 、 水 为溶剂， 以96%的产率得到3-[5-(4-Trifluoromethoxy-phenyl)-[1,2,4]-oxadiazol-3-ylmethoxy]-benzaldehyde oxime
  参考文献：
  名称：

  Di-oxadiazolidine derivatives as antihyperglycemic agents

  摘要：

  本发明涉及一种新型2-[4-(5-取代-1,2,4-噁二唑-3-基甲氧基)苯甲基]-1,2,5-噁二唑烷-3,5-二酮化合物，该化合物在糖尿病(ob/ob和db/db)小鼠中表现出抗高血糖活性，该小鼠是非胰岛素依赖性糖尿病（NIDDM或2型糖尿病）的遗传动物模型。该化合物由下式I表示：##STR1##其中R1是C6-C10芳基，可选地被一个至三个取自C1-C6烷基，C1-C6烷氧基，氟，氯，溴，碘，C1-C3三氟甲基或C1-C3三氟甲氧基的取代基独立取代；R2选自氢，C1-C6烷基，氟，氯，溴，碘，C1-C6烷氧基，C1-C3三氟甲基和C1-C3三氟甲氧基，或其药学上可接受的盐。

  公开号：

  US05420146A1
• 作为产物：
  描述：

  间羟基苯甲醛 、 3-Chloromethyl-5-(4-trifluoromethoxy-phenyl)-[1,2,4]oxadiazole 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 3-[5-(4-trifluoromethoxy-phenyl)-[1,2,4]-oxadiazol-3-ylmethoxy]-benzaldehyde
  参考文献：
  名称：

  Antihyperglycemic activity of new 1,2,4-oxadiazolidine-3,5-diones

  摘要：

  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.

  DOI：

  10.1016/s0223-5234(00)01191-0

文献信息

• Di-oxadiazolidine derivatives as antihyperglycemic agents
  申请人：American Home Products Corporation

  公开号：US05420146A1

  公开（公告）日：1995-05-30

  This invention relates to novel 2-[4-(5-substituted-1,2,4-oxadiazol-3-ylmethoxy)benzyl]-1,2,5-oxadiazolidi ne-3,5-diones which have demonstrated antihyperglycemic activity in diabetic (ob/ob and db/db) mice, genetic animal models of non-insulin dependent diabetes mellitus (NIDDM or Type II diabetes). These compounds are represented by Formula I below: ##STR1## wherein R.sup.1 is C.sub.6 -C.sub.10 aryl, optionally substituted by one to three substituents independently selected from C.sub.1 -C.sub.6 alkyl, C.sub.1 -C.sub.6 alkoxy, fluorine, chlorine, bromine, iodine, C.sub.1 -C.sub.3 trifluoroalkyl or C.sub.1 -C.sub.3 trifluoroalkoxy; and R.sup.2 is selected from the group consisting of hydrogen, C.sub.1 -C.sub.6 alkyl, fluorine, chlorine, bromine, iodine, C.sub.1 -C.sub.6 alkoxy, C.sub.1 -C.sub.3 trifluoroalkyl, and C.sub.1 -C.sub.3 trifluoroalkoxy, or a pharmaceutically acceptable salt thereof.

  本发明涉及一种新型2-[4-(5-取代-1,2,4-噁二唑-3-基甲氧基)苯甲基]-1,2,5-噁二唑烷-3,5-二酮化合物，该化合物在糖尿病(ob/ob和db/db)小鼠中表现出抗高血糖活性，该小鼠是非胰岛素依赖性糖尿病（NIDDM或2型糖尿病）的遗传动物模型。该化合物由下式I表示：##STR1##其中R1是C6-C10芳基，可选地被一个至三个取自C1-C6烷基，C1-C6烷氧基，氟，氯，溴，碘，C1-C3三氟甲基或C1-C3三氟甲氧基的取代基独立取代；R2选自氢，C1-C6烷基，氟，氯，溴，碘，C1-C6烷氧基，C1-C3三氟甲基和C1-C3三氟甲氧基，或其药学上可接受的盐。
• NEW DI-OXADIAZOLE DERIVATIVES AS ANTIHYPERGLYCEMIC AGENTS
  申请人：AMERICAN HOME PRODUCTS CORPORATION

  公开号：EP0759912A1

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

  公开号：EP0759912B1

  公开（公告）日：1998-11-25
• US5420146A
  申请人：——

  公开号：US5420146A

  公开（公告）日：1995-05-30
• [EN] NEW DI-OXADIAZOLE DERIVATIVES AS ANTIHYPERGLYCEMIC AGENTS<br/>[FR] NOUVEAUX DERIVES DU DI-OXADIAZOLE COMME AGENTS ANTIHYPERGLYCEMIQUES
  申请人：AMERICAN HOME PRODUCTS CORPORATION

  公开号：WO1995030664A1

  公开（公告）日：1995-11-16

  (EN) This invention relates to novel 2-[4-(5-substituted-1,2,4-oxadiazol-3-ylmethoxy)benzyl]-1,2,5-oxadiazolidine-3,5-diones which have demonstrated antihyperglycemic activity in diabetic (ob/ob and db/db) mice, genetic animal models of non-insulin dependent diabetes mellitus (NDDM or Type II diabetes). These compounds are represented by Formula (I), wherein R1 is C6-C10 aryl, optionally substituted by one to three substituents independently selected from C1-C6 alkyl, C1-C6 alkoxy, fluorine, chlorine, bromine, iodine, C1-C3 trifluoroalkyl or C1-C3 trifluoroalkoxy; and R2 is selected from the group consisting of hydrogen, C1-C6 alkyl, fluorine, chlorine, bromine, iodine, C1-C6 alkoxy, C1-C3 trifluoroalkyl, and C1-C3 trifluoroalkoxy, or a pharmaceutically acceptable salt thereof.(FR) Cette invention concerne de nouvelles 2[4-(1,2,4-oxadiazol-3-ylméthoxy)benzyl]-1,2,5-oxadiazolidine-3,5-diones substituées en position 5 du groupe oxadiazole, ayant des propriétés antihyperglycémiques chez les souris diabétiques ob/ob et db/db, qui sont des modèles génétiques animaux du diabète du type II (ou diabète sucré non insulinodépendant). Ces composés sont représentés par la formule (I). Dans cette formule, R1 est un C6-C10aryle, portant éventuellement un à trois substituants choisis d'une manière indépendante parmi C1-C6alkyle, C1-C6alcoxy, fluoro, chloro, bromo, iodo, C1-C3-trifluoroalkyle et C1-C3-trifluoroalcoxy et R2 est choisi parmi l'hydrogène, C1-C6alkyle, fluoro, chloro, bromo, iodo, C1-C6alcoxy, C1-C3trifluoroalkyle et C1-C3trifluoroalcoxy. L'invention concerne également les sels de ces composés acceptables sur le plan pharmaceutique.