| 503168-14-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• CAS: 503168-14-7
• 化学式: C₁₈H₁₇NO₂
• 分子量: 279.338
• InChiKey: SGOQFNXFJABUQR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.02
• 重原子数：
  21.0
• 可旋转键数：
  4.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  53.09
• 氢给体数：
  2.0
• 氢受体数：
  1.0

反应信息

• 作为反应物：
  描述：

  4-氨基四氢-2H-吡喃-3-羧酸甲酯 、 在 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 、 N,N-二异丙基乙胺 作用下， 生成
  参考文献：
  名称：

  Potent, selective, orally bioavailable inhibitors of tumor necrosis factor-α converting enzyme (TACE): Discovery of indole, benzofuran, imidazopyridine and pyrazolopyridine P1′ substituents

  摘要：

  Potent and selective inhibitors of tumor necrosis factor-a converting enzyme ( TACE) were discovered with several new heterocyclic P1' groups in conjunction with cyclic beta-amino hydroxamic acid scaffolds. Among them, the pyrazolopyridine provided the best overall profile when combined with tetrahydropyran beta-amino hydroxamic acid scaffold. Specifically, inhibitor 49 showed IC50 value of 1 nM against porcine TACE and 170 nM in the suppression of LPS-induced TNF-alpha of human whole blood. Compound 49 also displayed excellent selectivity over a wide panel of MMPs as well as excellent oral bioavailability (F% > 90%) in rat n-in-1 PK studies. (C) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2008.01.120
• 作为产物：
  描述：

  在 lithium hydroxide 作用下， 生成
  参考文献：
  名称：

  Potent, selective, orally bioavailable inhibitors of tumor necrosis factor-α converting enzyme (TACE): Discovery of indole, benzofuran, imidazopyridine and pyrazolopyridine P1′ substituents

  摘要：

  Potent and selective inhibitors of tumor necrosis factor-a converting enzyme ( TACE) were discovered with several new heterocyclic P1' groups in conjunction with cyclic beta-amino hydroxamic acid scaffolds. Among them, the pyrazolopyridine provided the best overall profile when combined with tetrahydropyran beta-amino hydroxamic acid scaffold. Specifically, inhibitor 49 showed IC50 value of 1 nM against porcine TACE and 170 nM in the suppression of LPS-induced TNF-alpha of human whole blood. Compound 49 also displayed excellent selectivity over a wide panel of MMPs as well as excellent oral bioavailability (F% > 90%) in rat n-in-1 PK studies. (C) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2008.01.120