(2S,3S)-2-amino-N-(1H-benzimidazol-2-ylmethyl)-3-methylpentanamide | 135832-61-0

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: (2S,3S)-2-amino-N-(1H-benzimidazol-2-ylmethyl)-3-methylpentanamide
• CAS: 135832-61-0
• 化学式: C₁₄H₂₀N₄O
• 分子量: 260.339
• InChiKey: BWAYDBAZNMHLPT-ZANVPECISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  19
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  83.8
• 氢给体数：
  3
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  异唑-5-羧酸 、 (2S,3S)-2-amino-N-(1H-benzimidazol-2-ylmethyl)-3-methylpentanamide 、 丁氧羰基--环乙基-丙氨酸-羟基盐酸盐 在 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 1.17h， 生成 N-[(2S)-1-[[(2S,3S)-1-(1H-benzimidazol-2-ylmethylamino)-3-methyl-1-oxopentan-2-yl]amino]-3-cyclohexyl-1-oxopropan-2-yl]-1,2-oxazole-5-carboxamide
  参考文献：
  名称：

  Benzylamide antagonists of protease activated receptor 2 with anti-inflammatory activity

  摘要：

  Activation of protease activated receptor 2 (PAR2) has been implicated in inflammatory and metabolic disorders and its inhibition may yield novel therapeutics. Here, we report a series of PAR2 antagonists based on C-terminal capping of 5-isoxazolyl-L-cyclohexylalanine-L-isoleucine, with benzylamine analogues being effective new PAR2 antagonists. 5-Isoxazolyl-L-cyclohexylalanine-L-isoleucine-2-methoxy-benzylamine (10) inhibited PAR2-, but not PAR1-, induced release of Ca2+ (IC50 0.5 mu M) in human colon cells, IL-6 and TNF alpha secretion (IC50 1-5 mu M) from human kidney cells, and was anti-inflammatory in acute rat paw inflammation (ED50 5 mg/kg sc). These findings show that new benzylamide antagonists of PAR2 have anti-inflammatory activity. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2015.12.048
• 作为产物：
  描述：

  (1H-苯并咪唑-2-亚甲基)胺 在 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 N,N-二异丙基乙胺 、 三氟乙酸 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 1.17h， 生成 (2S,3S)-2-amino-N-(1H-benzimidazol-2-ylmethyl)-3-methylpentanamide
  参考文献：
  名称：

  Benzylamide antagonists of protease activated receptor 2 with anti-inflammatory activity

  摘要：

  Activation of protease activated receptor 2 (PAR2) has been implicated in inflammatory and metabolic disorders and its inhibition may yield novel therapeutics. Here, we report a series of PAR2 antagonists based on C-terminal capping of 5-isoxazolyl-L-cyclohexylalanine-L-isoleucine, with benzylamine analogues being effective new PAR2 antagonists. 5-Isoxazolyl-L-cyclohexylalanine-L-isoleucine-2-methoxy-benzylamine (10) inhibited PAR2-, but not PAR1-, induced release of Ca2+ (IC50 0.5 mu M) in human colon cells, IL-6 and TNF alpha secretion (IC50 1-5 mu M) from human kidney cells, and was anti-inflammatory in acute rat paw inflammation (ED50 5 mg/kg sc). These findings show that new benzylamide antagonists of PAR2 have anti-inflammatory activity. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2015.12.048

文献信息

• Benzylamide antagonists of protease activated receptor 2 with anti-inflammatory activity
  作者：Mei-Kwan Yau、Ligong Liu、Junxian Lim、Rink-Jan Lohman、Adam J. Cotterell、Jacky Y. Suen、David A. Vesey、Robert C. Reid、David P. Fairlie

  DOI：10.1016/j.bmcl.2015.12.048

  日期：2016.2

  Activation of protease activated receptor 2 (PAR2) has been implicated in inflammatory and metabolic disorders and its inhibition may yield novel therapeutics. Here, we report a series of PAR2 antagonists based on C-terminal capping of 5-isoxazolyl-L-cyclohexylalanine-L-isoleucine, with benzylamine analogues being effective new PAR2 antagonists. 5-Isoxazolyl-L-cyclohexylalanine-L-isoleucine-2-methoxy-benzylamine (10) inhibited PAR2-, but not PAR1-, induced release of Ca2+ (IC50 0.5 mu M) in human colon cells, IL-6 and TNF alpha secretion (IC50 1-5 mu M) from human kidney cells, and was anti-inflammatory in acute rat paw inflammation (ED50 5 mg/kg sc). These findings show that new benzylamide antagonists of PAR2 have anti-inflammatory activity. (C) 2015 Elsevier Ltd. All rights reserved.