5-isoxazoyl-Cha-Ile-amino-3-[(pyridin-3-yl)methylamino]propan-3-one | 1252806-66-8

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 肽模拟物
• 英文名称: 5-isoxazoyl-Cha-Ile-amino-3-[(pyridin-3-yl)methylamino]propan-3-one
• 英文别名: N-[(2S)-3-cyclohexyl-1-[[(2S,3S)-3-methyl-1-oxo-1-[[3-oxo-3-(pyridin-3-ylmethylamino)propyl]amino]pentan-2-yl]amino]-1-oxopropan-2-yl]-1,2-oxazole-5-carboxamide
• CAS: 1252806-66-8
• 化学式: C₂₈H₄₀N₆O₅
• 分子量: 540.663
• InChiKey: LKLAWBBOIMKCMU-JTJYXVOQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  39
• 可旋转键数：
  14
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  155
• 氢给体数：
  4
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  3-氨甲基吡啶 、 在 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 5-isoxazoyl-Cha-Ile-amino-3-[(pyridin-3-yl)methylamino]propan-3-one
  参考文献：
  名称：

  Novel Agonists and Antagonists for Human Protease Activated Receptor 2

  摘要：

  Human protease activated receptor 2 (PAR2) is a G protein-coupled receptor that is associated with inflammatory diseases and cancers. PAR2 is activated by serine proteases that cleave its N-terminus and by synthetic peptides corresponding to the new N-terminus. Peptide agonists are widely used to characterize physiological roles for PAR2 but typically have low potency (e.g., SLICK V-NH2, SLIGRL-NH2), uncertain target selectivity, and poor bioavailability, limiting their usefulness for specifically interrogating PAR2 in vivo. Structure-activity relationships were used to derive new PAR2 agonists and antagonists containing nonpeptidic moieties. Agonist GB110 (19, EC50 0.28 mu M) selectively induced PAR2-, but not PAR1-, mediated intracellular Ca2+ release in HT29 human colorectal carcinoma cells. Antagonist GB83 (36, IC50 2 mu M) is the first compound at micromolar concentrations to reversibly inhibit PAR2 activation by both proteases and other PAR2 agonists (e.g., trypsin, 2f-furoyl-LIGRLO-NH2, 19). The new compounds are selective for PAR2 over PAR1, serum stable, and suitable for modulating PAR2 in disease models.

  DOI：

  10.1021/jm100984y

文献信息

• Novel Agonists and Antagonists for Human Protease Activated Receptor 2
  作者：Grant D. Barry、Jacky Y. Suen、Giang T. Le、Adam Cotterell、Robert C. Reid、David P. Fairlie

  DOI：10.1021/jm100984y

  日期：2010.10.28

  Human protease activated receptor 2 (PAR2) is a G protein-coupled receptor that is associated with inflammatory diseases and cancers. PAR2 is activated by serine proteases that cleave its N-terminus and by synthetic peptides corresponding to the new N-terminus. Peptide agonists are widely used to characterize physiological roles for PAR2 but typically have low potency (e.g., SLICK V-NH2, SLIGRL-NH2), uncertain target selectivity, and poor bioavailability, limiting their usefulness for specifically interrogating PAR2 in vivo. Structure-activity relationships were used to derive new PAR2 agonists and antagonists containing nonpeptidic moieties. Agonist GB110 (19, EC50 0.28 mu M) selectively induced PAR2-, but not PAR1-, mediated intracellular Ca2+ release in HT29 human colorectal carcinoma cells. Antagonist GB83 (36, IC50 2 mu M) is the first compound at micromolar concentrations to reversibly inhibit PAR2 activation by both proteases and other PAR2 agonists (e.g., trypsin, 2f-furoyl-LIGRLO-NH2, 19). The new compounds are selective for PAR2 over PAR1, serum stable, and suitable for modulating PAR2 in disease models.