N-[4-(2-{4-[(2-amino-1H-imidazol-4-yl)ethyl]phenyl}ethyl)thiazol-2-yl]acetamide hydrochloride | 1442469-26-2

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: N-[4-(2-{4-[(2-amino-1H-imidazol-4-yl)ethyl]phenyl}ethyl)thiazol-2-yl]acetamide hydrochloride
• 英文别名: N-[4-[2-[4-[2-(2-amino-1H-imidazol-5-yl)ethyl]phenyl]ethyl]-1,3-thiazol-2-yl]acetamide;hydrochloride
• CAS: 1442469-26-2
• 化学式: C₁₈H₂₁N₅OS*ClH
• 分子量: 391.925
• InChiKey: XJJOUTSZDUKCFW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  26
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.28
• 拓扑面积：
  125
• 氢给体数：
  4
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  tert-butyl (4-{4-[2-(2-acetamido-1,3-thiazol-4-yl)ethyl]phenethyl}-1H-imidazol-2-yl)carbamate 在 盐酸 作用下， 以 甲醇 、 水 、 乙酸乙酯 为溶剂， 反应 10.0h， 以96%的产率得到N-[4-(2-{4-[(2-amino-1H-imidazol-4-yl)ethyl]phenyl}ethyl)thiazol-2-yl]acetamide hydrochloride
  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

• 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.