N-[4-(2-{4-[(2-amino-1H-imidazol-4-yl)methyl]phenyl}ethyl)thiazol-2-yl]acetamide hydrochloride | 1442469-25-1

• 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)methyl]phenyl}ethyl)thiazol-2-yl]acetamide hydrochloride
• 英文别名: N-[4-[2-[4-[(2-amino-1H-imidazol-5-yl)methyl]phenyl]ethyl]-1,3-thiazol-2-yl]acetamide;hydrochloride
• CAS: 1442469-25-1
• 化学式: C₁₇H₁₉N₅OS*ClH
• 分子量: 377.898
• InChiKey: XYQWAISRHSHNND-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  25
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.24
• 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]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

文献信息

• NICOTINYL RIBOSIDE COMPOUNDS AND THEIR USES
  申请人：MitoPower, LLC

  公开号：US20200397807A1

  公开（公告）日：2020-12-24

  The disclosure provides nicotinamide riboside (NR), the reduced form of NR (NRH), nicotinic acid riboside (NAR), the reduced form of NAR (NARH), derivatives thereof, compositions thereof and uses thereof. The NR and NAR derivatives have improved stability and bioavailability compared to NR and NAR. NR, NRH, NAR, NARH, and derivatives thereof can increase cellular NAD + levels and enhance mitochondrial and cellular function and cell viability. Therefore, NR, NRH, NAR, NARH, and derivatives thereof, whether alone or in combination with one or more additional therapeutic agents (e.g., a mitochondrial uncoupler or/and a PARP inhibitor), are useful for treating mitochondrial diseases, mitochondria-related diseases and conditions, metabolic disorders, and other disorders and conditions.

  该披露提供烟酰胺核糖苷（NR）、烟酰胺核糖苷的还原形式（NRH）、烟酸核糖苷（NAR）、烟酸核糖苷的还原形式（NARH）、以及它们的衍生物、组合物和用途。与NR和NAR相比，NR和NAR的衍生物具有更好的稳定性和生物利用度。NR、NRH、NAR、NARH和它们的衍生物可以增加细胞NAD+水平，增强线粒体和细胞功能以及细胞存活能力。因此，NR、NRH、NAR、NARH和它们的衍生物，无论是单独使用还是与一个或多个额外治疗剂（例如线粒体解耦蛋白抑制剂和/或PARP抑制剂）结合使用，都可用于治疗线粒体疾病、与线粒体相关的疾病和症状、代谢紊乱以及其他疾病和症状。
• [EN] NICOTINYL RIBOSIDE COMPOUNDS AND THEIR USES<br/>[FR] COMPOSÉS NICOTINYL RIBOSIDE ET LEURS UTILISATIONS
  申请人：MITOPOWER LLC

  公开号：WO2020257283A1

  公开（公告）日：2020-12-24

  The disclosure provides nicotinamide riboside (NR), the reduced form of NR (NRH), nicotinic acid riboside (NAR), the reduced form of NAR (NARH), derivatives thereof, compositions thereof and uses thereof. The NR and NAR derivatives have improved stability and bioavailability compared to NR and NAR. NR, NRH, NAR, NARH, and derivatives thereof can increase cellular NAD+ levels and enhance mitochondrial and cellular function and cell viability. Therefore, NR, NRH, NAR, NARH, and derivatives thereof, whether alone or in combination with one or more additional therapeutic agents (e.g., a mitochondrial uncoupler or/and a PARP inhibitor), are useful for treating mitochondrial diseases, mitochondria-related diseases and conditions, metabolic disorders, and other disorders and conditions.
• 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.