3-{4-[2-(2-acetamido-1,3-thiazol-4-yl)ethyl]phenyl}propanoic acid | 874901-16-3

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 苯丙酸
• 英文名称: 3-{4-[2-(2-acetamido-1,3-thiazol-4-yl)ethyl]phenyl}propanoic acid
• 英文别名: 3-(4-{2-[2-(acetylamino)-1,3-thiazol-4-yl]ethyl}phenyl)propanoic acid；3-(4-{2-[2-(Acetylamino)-1,3-thiazol-4-yl]ethyl}phenyl)propanoic acid；3-[4-[2-(2-acetamido-1,3-thiazol-4-yl)ethyl]phenyl]propanoic acid
• CAS: 874901-16-3
• 化学式: C₁₆H₁₈N₂O₃S
• 分子量: 318.397
• InChiKey: PWTMJIAJPCGXAC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  22
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  108
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  3-{4-[2-(2-acetamido-1,3-thiazol-4-yl)ethyl]phenyl}propanoic acid 以 正己烷 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 22.08h， 生成 tert-butyl (4-{4-[2-(2-acetamido-1,3-thiazol-4-yl)ethyl]phenethyl}-1H-imidazol-2-yl)carbamate
  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
• 作为产物：
  描述：

  {[2-(acetylamino)-1,3-thiazol-4-yl]methyl}(triphenyl)phosphonium chloride 在 palladium 10% on activated carbon 、 potassium tert-butylate 、 氢气 、 sodium hydroxide 作用下， 以 1,4-二氧六环 、 水 、 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 21.25h， 生成 3-{4-[2-(2-acetamido-1,3-thiazol-4-yl)ethyl]phenyl}propanoic acid
  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

• Thiazole Derivatives Having Vap-1 Inhibitory Activity
  申请人：Inoue Takayuki

  公开号：US20070254931A1

  公开（公告）日：2007-11-01

  A compound of the formula (I), (II), (III) or (IV): 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 subject, and the like.

  公式（I），（II），（III）或（IV）的化合物：其中每个符号如规范中所定义，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，制药组合物，预防或治疗VAP-1相关疾病，特别是黄斑水肿的方法，该方法包括向受试者投予化合物或其药学上可接受的盐的有效量等。
• [EN] THIAZOLE DERIVATIVES HAVING VAP-1 INHIBITORY ACTIVITY<br/>[FR] DERIVES DE THIAZOLE PRESENTANT UNE ACTIVITE D'INHIBITION DE LA VAP-1
  申请人：ASTELLAS PHARMA INC

  公开号：WO2006011631A3

  公开（公告）日：2006-04-20
• THIAZOLE DERIVATIVES HAVING VAP-1 INHIBITORY ACTIVITY
  申请人：Astellas Pharma Inc.

  公开号：EP1786792B1

  公开（公告）日：2009-04-08
• Novel 1H-imidazol-2-amine derivatives as potent and orally active vascular adhesion protein-1 (VAP-1) inhibitors for diabetic macular edema treatment
  作者：Takayuki Inoue、Masataka Morita、Takashi Tojo、Akira Nagashima、Ayako Moritomo、Hiroshi Miyake

  DOI：10.1016/j.bmc.2013.04.011

  日期：2013.7

  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.