tert-butyl (4-{4-[2-(2-acetamido-1,3-thiazol-4-yl)ethyl]benzyl}-1H-imidazol-2-yl)carbamate | 1442469-22-8

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: tert-butyl (4-{4-[2-(2-acetamido-1,3-thiazol-4-yl)ethyl]benzyl}-1H-imidazol-2-yl)carbamate
• CAS: 1442469-22-8
• 化学式: C₂₂H₂₇N₅O₃S
• 分子量: 441.554
• InChiKey: ZZZCMAVUFHNYPC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.55
• 重原子数：
  31.0
• 可旋转键数：
  7.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  109.0
• 氢给体数：
  3.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  tert-butyl (4-{4-[2-(2-acetamido-1,3-thiazol-4-yl)ethyl]benzyl}-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74%的产率得到N-[4-(2-{4-[(2-amino-1H-imidazol-4-yl)methyl]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
• 作为产物：
  描述：

  {4-[2-(2-acetamido-1,3-thiazol-4-yl)ethyl]phenyl}acetic 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]benzyl}-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