(Z)-2-Methyl-3-{3-[5-methyl-2-(4-trifluoromethyl-phenyl)-oxazol-4-ylmethoxy]-phenyl}-but-2-enoic acid ethyl ester | 174258-80-1

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 肉桂酸及其衍生物
• 英文名称: (Z)-2-Methyl-3-{3-[5-methyl-2-(4-trifluoromethyl-phenyl)-oxazol-4-ylmethoxy]-phenyl}-but-2-enoic acid ethyl ester
• 英文别名: ethyl (Z)-2-methyl-3-[3-[[5-methyl-2-[4-(trifluoromethyl)phenyl]-1,3-oxazol-4-yl]methoxy]phenyl]but-2-enoate
• CAS: 174258-80-1
• 化学式: C₂₅H₂₄F₃NO₄
• 分子量: 459.465
• InChiKey: DQMIBEUHYGKVRS-NXVVXOECSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.4
• 重原子数：
  33
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.28
• 拓扑面积：
  61.6
• 氢给体数：
  0
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  (Z)-2-Methyl-3-{3-[5-methyl-2-(4-trifluoromethyl-phenyl)-oxazol-4-ylmethoxy]-phenyl}-but-2-enoic acid ethyl ester 在 二异丁基氢化铝 、 三苯基膦 、 偶氮二甲酸二乙酯 作用下， 以 四氢呋喃 、 乙醚 为溶剂， 反应 1.5h， 生成 tert-butyl [[(Z)-2-methyl-3-[3-[[5-methyl-2-[4-(trifluoromethyl)phenyl]-1,3-oxazol-4-yl]methoxy]phenyl]but-2-enyl]-[(2-methylpropan-2-yl)oxycarbonyl]amino] carbonate
  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：

  4-(氯甲基)-5-甲基-2-[4-(三氟甲基)苯基]-1,3-噁唑 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 (Z)-2-Methyl-3-{3-[5-methyl-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

文献信息

• AZOLIDINEDIONES AS ANTIHYPERGLYCEMIC AGENTS
  申请人：AMERICAN HOME PRODUCTS CORPORATION

  公开号：EP0759919B1

  公开（公告）日：1998-11-11
• US5468762A
  申请人：——

  公开号：US5468762A

  公开（公告）日：1995-11-21
• US5532256A
  申请人：——

  公开号：US5532256A

  公开（公告）日：1996-07-02
• [EN] NEW AZOLIDINEDIONES AS ANTIHYPERGLYCEMIC AGENTS<br/>[FR] NOUVELLES AZOLIDINEDIONES UTILES COMME AGENTS ANTIHYPERGLYCEMIQUES
  申请人：AMERICAN HOME PRODUCTS CORPORATION

  公开号：WO1995031454A1

  公开（公告）日：1995-11-23

  (EN) 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 or Type II diabetes). These compounds have formula (I), wherein: R1 is C1-C6 alkyl, C3-C8 cycloalkyl, thienyl, furyl, pyridyl, (a) or (b), where R10 is hydrogen, C1-C6 alkyl, fluorine, chlorine, bromine, iodine, C1-C6 alkyoxy, trifluoroalkyl or trifluoroalkoxy; R2 is hydrogen or C1-C6 alkyl; X is O or S; n is 0, 1, or 2; A is (c) or (d); where R3 is hydrogen, C1-C6 alkyl, halogen, C1-C6 alkoxy, trifluoroalkyl or trifluoroalkoxy; B is (e), (f) or (g), where R4 is hydrogen, C1-C6 alkyl, allyl, C6-C10 aryl, C6-C10 aryl-(CH2)1-6-, fluorine, chlorine, bromine, iodine, trimethylsilyl or C3-C8 cycloalkyl; R5 is hydrogen, C1-C6 alkyl, C6-C10 aryl, or C6-C10 aryl-(CH2)1-6-; m is 0, 1, or 2; R6 is hydrogen or C1-C6 alkyl; R7 is hydrogen or C1-C6 alkyl; R8 and R9 are selected independently from hydrogen, C1-C6 alkyl, fluorine, chlorine, bromine, or iodine; 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.(FR) Cette invention concerne de nouveaux composés ou un sel pharmaceutiquement acceptable de ces derniers qui ont fait preuve d'une activité antihyperglycémique orale chez des souris diabétiques ob/ob et db/db, des modèles d'animaux souffrant de diabète sucré non insulino-dépendant (DSNID ou de diabète du type II). Ces composés répondent à la formule I, dans laquelle R1 représente alkyle C1-C6, cycloalkyle C3-C8, thiényle, furyle, pyridyle, (a) or (b) dans laquelle R10 représente hydrogène, alkyle C1-C6, fluor, chlore, brome, iode, alkyoxy C1-C6, trifluoroalkyle ou trifluoroalcoxy; R2 représente hydrogène ou alkyle C1-C6; X représente O ou S; n représente 0, 1 ou 2; A représente (c) ou (d), dans laquelle R3 représente hydrogène, alkyle C1-C6, halogène, alcoxy C1-C6, trifluoroalkyle ou trifluoroalcoxy; B représente (e), (f), (g) dans laquelle R4 représente hydrogène, alkyle C1-C6, allyle, aryle C6-C10, aryle C6-C10-(CH2)1-6-, fluor, chlore, brome, iode, triméthylsilyle ou cycloalkyle C3-C8; R5 représentant hydrogène, alkyle C1-C6, aryle C6-C10, ou aryle C6-C10-(CH2)1-6; m représente 0, 1 ou 2; R6 représente hydrogène ou alkyle C1-C6; R7 représente hydrogène ou alkyle C1-C6; R8 et R9 étant sélectionnés indépendamment parmi hydrogène, alkyle C1-C6, fluor, chlore, brome et iode; Y représente O ou S; Z représente N ou CH quand Y représente O et Z représente CH quand Y représente S.
• New Azolidinediones as Inhibitors of Protein Tyrosine Phosphatase 1B with Antihyperglycemic Properties
  作者：Michael S. Malamas、Janet Sredy、Iwan Gunawan、Brenda Mihan、Diane R. Sawicki、Laura Seestaller、Donald Sullivan、Brenda R. Flam

  DOI：10.1021/jm990476x

  日期：2000.3.1

  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.