methyl 4-[2-(2-acetamido-1,3-thiazol-4-yl)ethyl]benzoate | 737823-39-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: methyl 4-[2-(2-acetamido-1,3-thiazol-4-yl)ethyl]benzoate
• 英文别名: methyl 4-[2-(2-acetylaminothiazol-4-yl)ethyl]benzoate；methyl 4-{2-[2-(acetylamino)-1,3-thiazol-4-yl]ethyl}benzoate
• CAS: 737823-39-1
• 化学式: C₁₅H₁₆N₂O₃S
• 分子量: 304.37
• InChiKey: MSWXDUDLFLNZNM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  21
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  96.5
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  methyl 4-[2-(2-acetamido-1,3-thiazol-4-yl)ethyl]benzoate 在 二异丁基氢化铝 作用下， 以 四氢呋喃 、 甲苯 为溶剂， 反应 1.75h， 生成 N-(4-{2-[4-(hydroxymethyl)phenyl]ethyl}thiazol-2-yl)acetamide
  参考文献：
  名称：

  [EN] THIAZOLE DERIVATIVES AND THEIR USE AS VAP-1 INHIBITORS
  [FR] DERIVES DE THIAZOLE ET LEUR UTILISATION EN TANT QU'INHIBITEURS DE VAP-1

  摘要：

  一种化合物的分子式（I）：R1-NH-X-Y-Z（I），其中R1为酰基；X为可选取代噻唑衍生的双价残基；Y为键，较低的烷基或-COHN-；Z为分子式（II）或（III）中的基团，其中R2为特定的取代基或其药用可接受的盐，用作预防或治疗与血管粘附蛋白-1（VAP-1）相关的疾病的VAP-1抑制剂，特别是黄斑水肿。

  公开号：

  WO2004067521A1
• 作为产物：
  描述：

  (4-甲氧羰基苄基)三苯基溴化膦 在 palladium 10% on activated carbon 、 potassium tert-butylate 、 氢气 作用下， 以 溶剂黄146 、 N,N-二甲基甲酰胺 为溶剂， 20.0 ℃ 、303.99 kPa 条件下， 反应 19.25h， 生成 methyl 4-[2-(2-acetamido-1,3-thiazol-4-yl)ethyl]benzoate
  参考文献：
  名称：

  Novel 1H-imidazol-2-amine derivatives as potent and orally active vascular adhesion protein-1 (VAP-1) inhibitors for diabetic macular edema treatment

  摘要：

  Novel thiazole derivatives were synthesized and evaluated as vascular adhesion protein-1 (VAP-1) inhibitors. Although we previously identified a compound (2) with potent VAP-1 inhibitory activity in rats, the human activity was relatively weak. Here, to improve the human VAP-1 inhibitory activity of compound 2, we first evaluated the structure-activity relationships of guanidine bioisosteres as simple small molecules and identified a 1H-benzimidazol-2-amine (5) with potent activity compared to phenylguanidine (1). Based on the structure of compound 5, we synthesized a highly potent VAP-1 inhibitor (37b; human IC50 = 0.019 mu M, rat IC50 = 0.0051 mu M). Orally administered compound 37b also markedly inhibited ocular permeability in streptozotocin-induced diabetic rats after oral administration, suggesting it is a promising compound for the treatment of diabetic macular edema. (C) 2013 The Authors. Published by Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2013.04.011

文献信息

• [EN] THIAZOLE DERIVATIVES AND THEIR USE AS VAP-1 INHIBITORS<br/>[FR] DERIVES DE THIAZOLE ET LEUR UTILISATION EN TANT QU'INHIBITEURS DE VAP-1
  申请人：FUJISAWA PHARMACEUTICAL CO

  公开号：WO2004067521A1

  公开（公告）日：2004-08-12

  A compound of the formula (I): R1-NH-X-Y-Z (I) wherein R1 is acyl; X is a bivalent residue derived from optionally substituted thiazole; Y is a bond, lower alkylene or -COHN-; and Z is a groupe of the formulae (II) or (III) wherein R2 is a specified substituent or a pharmaceutically acceptable salt thereof useful as a vascular adhesion protein-1 (VAP-1) inhibitor for preventing or treating a VAP-1associated disease, especially macular edema.

  一种化合物的分子式（I）：R1-NH-X-Y-Z（I），其中R1为酰基；X为可选取代噻唑衍生的双价残基；Y为键，较低的烷基或-COHN-；Z为分子式（II）或（III）中的基团，其中R2为特定的取代基或其药用可接受的盐，用作预防或治疗与血管粘附蛋白-1（VAP-1）相关的疾病的VAP-1抑制剂，特别是黄斑水肿。
• Thiazole derivatives
  申请人：Inoue Takayuki

  公开号：US20060128770A1

  公开（公告）日：2006-06-15

  A compound of the formula (I): R 1 —NH—X—Y-Z (I) wherein each symbol is as defined in the specification, or a pharmaceutically acceptable salt thereof useful as a vascular adhesion protein-1 (VAP-1) inhibitor, a pharmaceutical composition, a method for preventing or treating a VAP-1 associated disease, especially macular edema, which method includes administering an effective amount of the compound or a pharmaceutically acceptable salt thereof to a mammal, and the like.

  化合物公式(I): R1—NH—X—Y-Z (I)，其中每个符号如规范所定义，或其药学上可接受的盐，可用作血管黏附蛋白-1（VAP-1）抑制剂，制备一种制药组合物，一种预防或治疗VAP-1相关疾病（尤其是黄斑水肿）的方法，该方法包括向哺乳动物投与化合物或其药学上可接受的盐的有效量等。
• Method for treating vascular hyperpermeable disease
  申请人：Ueno Ryuji

  公开号：US20060229346A1

  公开（公告）日：2006-10-12

  The present invention provides a method for treating a vascular hyperpermeable disease (except macular edema), which method comprises administering to a patient in need thereof a vascular adhesion protein-1 (VAP-1) inhibitor in an amount sufficient to treat said patient for said disease. The agents are 2-acylamino thiazole compounds.

  本发明提供了一种治疗血管过渗性疾病（除黄斑水肿外）的方法，该方法包括向需要治疗该疾病的患者施用足量的血管粘附蛋白-1（VAP-1）抑制剂。该抑制剂为2-酰胺基噻唑类化合物。
• METHOD FOR TREATING VASCULAR HYPERPERMEABLE DISEASE
  申请人：UENO Ryuji

  公开号：US20080119462A1

  公开（公告）日：2008-05-22

  The present invention provides a method for treating a vascular hyperpermeable disease (except macular edema), which method comprises administering to a patient in need thereof a vascular adhesion protein-1 (VAP-1) inhibitor in an amount sufficient to treat said patient for said disease.

  本发明提供了一种治疗血管过渗性疾病（除了黄斑水肿）的方法，该方法包括向需要治疗该疾病的患者施用足够治疗该疾病的血管粘附蛋白-1（VAP-1）抑制剂。
• Thiazole Derivatives Having Vap-1 Inhibitory Activity
  申请人：Inoue Takayuki

  公开号：US20080015202A1

  公开（公告）日：2008-01-17

  A compound of the formula (I): U-V-W-X-Y-Z  (I) wherein U is lower alkyl; V is —CONH— or —NR 1 CO— wherein R 1 is a hydrogen or lower alkyl; W is a bond or lower alkylene; X is a bivalent residue derived from optionally substituted thiazole; Y is a bond or lower alkylene; and Z is a group of the formula: wherein R 2 is a group of the formula: -A-B-D-E-F-G wherein A is a bond or lower alkylene; B is a bond, —NH— or D is a bond, —CS— or —CO—; E is a bond or —NH—; F is a bond, —CO—, —O— or —SO 2 —; and G is lower alkyl, optionally protected amino, —OH, phenyl, R 3 is lower alkyl, provided that when Z is a group of the formula: then G should not be amino, when Z is a group of the formula: then G should not be when Z is a group of the formula: and G is optionally protected amino, then D should be —CS—, or then A should be lower alkylene, B or E should be —NH— and F should be —CO—; or a pharmaceutically acceptable salt thereof useful as a vascular adhesion protein-1 (VAP-1) inhibitor as well as a pharmaceutical composition and a method for preventing or treating a VAP-1 associated disease, especially macular edema, which method includes administering an effective amount of the compound or a pharmaceutically acceptable salt thereof to a subject, and the like.

  化合物的结构式（I）：U-V-W-X-Y-Z  （I），其中U为低级烷基；V为—CONH—或—NR1CO—，其中R1为氢或低级烷基；W为键或低级亚烷基；X为源自可选取代噻唑的二价残基；Y为键或低级亚烷基；Z为下式的基团：其中R2为下式的基团：-A-B-D-E-F-G，其中A为键或低级亚烷基；B为键，—NH—或D为键，—CS—或—CO—；E为键或—NH—；F为键，—CO—，—O—或—SO2—；G为低级烷基，可选的保护氨基，—OH，苯基，R3为低级烷基，但当Z为下式的基团时：则G不应为氨基；当Z为下式的基团时：则G不应为；当Z为下式的基团时：若G为可选的保护氨基，则D应为—CS—，或者A应为低级亚烷基，B或E应为—NH—，F应为—CO—；或其药学上可接受的盐，作为血管黏附蛋白-1（VAP-1）抑制剂以及用于预防或治疗VAP-1相关疾病，特别是黄斑水肿的制剂组合物和方法，该方法包括向受体施用化合物或其药学上可接受的盐的有效量等。