hydroxy{(E)-3-[3-({5-methyl-2-[4-(trifluoromethyl)phenyl]-1,3-oxazol-4-yl}methoxy)phenyl]-2-butenyl}carbamic acid | 174258-54-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: hydroxy{(E)-3-[3-({5-methyl-2-[4-(trifluoromethyl)phenyl]-1,3-oxazol-4-yl}methoxy)phenyl]-2-butenyl}carbamic acid
• 英文别名: (E)-N-(3-{3-[5-methyl-2-(4-trifluoromethyl-phenyl)-oxazol-4-ylmethoxy]phenyl}-but-2-enyl)-hydroxylamine；N-[(E)-3-[3-[[5-methyl-2-[4-(trifluoromethyl)phenyl]-1,3-oxazol-4-yl]methoxy]phenyl]but-2-enyl]hydroxylamine
• CAS: 174258-54-9
• 化学式: C₂₂H₂₁F₃N₂O₃
• 分子量: 418.416
• InChiKey: DAJFNSCXZWMACK-GXDHUFHOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  30
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  67.5
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  N-(氯甲酰)异氰酸酯 、 hydroxy{(E)-3-[3-({5-methyl-2-[4-(trifluoromethyl)phenyl]-1,3-oxazol-4-yl}methoxy)phenyl]-2-butenyl}carbamic acid 以 四氢呋喃 为溶剂， 反应 0.5h， 以62%的产率得到(E)-2-(3-{3-[5-methyl-2-(4-trifluoromethyl-phenyl)-oxazol-4-ylmethoxy]phenyl)-but-2-enyl)-[1,2,4]oxadiazolidine-3,5-dione
  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 、 二异丁基氢化铝 、 potassium carbonate 、 三苯基膦 、 三氟乙酸 、 偶氮二甲酸二乙酯 作用下， 以 四氢呋喃 、 乙醚 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 68.5h， 生成 hydroxy{(E)-3-[3-({5-methyl-2-[4-(trifluoromethyl)phenyl]-1,3-oxazol-4-yl}methoxy)phenyl]-2-butenyl}carbamic acid
  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
• 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.