1-(2-(N-imidazol-2-ylaminocarbonyl)ethyl)-5-carboxyindazole | 192945-45-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并吡唑类
• 英文名称: 1-(2-(N-imidazol-2-ylaminocarbonyl)ethyl)-5-carboxyindazole
• 英文别名: 1-[3-(1H-imidazol-2-ylamino)-3-oxopropyl]indazole-5-carboxylic acid
• CAS: 192945-45-2
• 化学式: C₁₄H₁₃N₅O₃
• 分子量: 299.289
• InChiKey: LQDCHNNZCITNJS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.3
• 重原子数：
  22
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  113
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  1-(2-(N-imidazol-2-ylaminocarbonyl)ethyl)-5-carboxyindazole 在 1-羟基苯并三唑 、 N,N'-二环己基碳二亚胺 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 24.0h， 生成 3-[1-[2-(N-imidazol-2-ylaminocarbonyl)ethyl]indazol-5-ylcarbonylamino]-2(S)-(2,4,6-trimethylbenzenesulfonylamino)propionic acid trifluoroacetate
  参考文献：
  名称：

  Disubstituted Indazoles as Potent Antagonists of the Integrin α_vβ₃

  摘要：

  A new series of indazole-containing alpha(v)beta(3) integrin antagonists is described. Starting with lead compound 18a, variations in a number of structural features were explored with respect to inhibition of the binding of beta(3)-transfected 293 cells to fibrinogen and to selectivity for alpha(v)beta(3) over GPIIbIIIa, another RGD-binding integrin. Indazoles attached to a 2-aminopyridine or 2-aminoimidazole by a propylene linker at the indazole 1-position and to a diaminopropionate derivative via a 5-carboxylate amide provided the best potency with moderate selectivity. Several differences in the SAR of the diaminopropionate moiety were observed between this series and a series of isoxazoline-based selective GPIIbIIIa antagonists. Compound 34a (SM256) was a potent antagonist of alpha(v)beta(3) (IC50 2.3 nM) with 9-fold selectivity over GPIIbIIIa.

  DOI：

  10.1021/jm990049j
• 作为产物：
  描述：

  1H-吲唑-5-甲酸乙酯 在 lithium hydroxide 、 potassium tert-butylate 、 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 、 叔丁醇 为溶剂， 反应 57.75h， 生成 1-(2-(N-imidazol-2-ylaminocarbonyl)ethyl)-5-carboxyindazole
  参考文献：
  名称：

  Disubstituted Indazoles as Potent Antagonists of the Integrin α_vβ₃

  摘要：

  A new series of indazole-containing alpha(v)beta(3) integrin antagonists is described. Starting with lead compound 18a, variations in a number of structural features were explored with respect to inhibition of the binding of beta(3)-transfected 293 cells to fibrinogen and to selectivity for alpha(v)beta(3) over GPIIbIIIa, another RGD-binding integrin. Indazoles attached to a 2-aminopyridine or 2-aminoimidazole by a propylene linker at the indazole 1-position and to a diaminopropionate derivative via a 5-carboxylate amide provided the best potency with moderate selectivity. Several differences in the SAR of the diaminopropionate moiety were observed between this series and a series of isoxazoline-based selective GPIIbIIIa antagonists. Compound 34a (SM256) was a potent antagonist of alpha(v)beta(3) (IC50 2.3 nM) with 9-fold selectivity over GPIIbIIIa.

  DOI：

  10.1021/jm990049j

文献信息

• Integrin receptor antagonists
  申请人：The DuPont Merck Pharmaceutical Company

  公开号：US05760028A1

  公开（公告）日：1998-06-02

  This invention relates to novel heterocycles including 3-\x9b1-\x9b3-(imidazolin-2-ylamino)propyl!indazol-5-ylcarbonylamino!-2-(benzylo xycarbonylamino)propionic acid, which are useful as antagonists of the .alpha..sub.v .beta..sub.3 integrin and related cell surface adhesive protein receptors, to pharmaceutical compositions containing such compounds, processes for preparing such compounds, and to methods of using these compounds, alone or in combination with other therapeutic agents, for the inhibition of cell adhesion, the treatment of angiogenic disorders, inflammation, bone degradation, cancer metastasis, diabetic retinopathy, thrombosis, restenosis, macular degeneration, and other conditions mediated by cell adhesion and/or cell migration and/or angiogenesis.

  本发明涉及新颖的杂环化合物，包括3-\x9b1-\x9b3-(咪唑啉-2-基氨基)丙基！吲唑-5-基羧酰胺!-2-(苄氧羰基氨基)丙酸，其作为.alpha..sub.v .beta..sub.3整合素及相关细胞表面粘附蛋白受体的拮抗剂具有用途。本发明还涉及含有这种化合物的药物组合物、制备这种化合物的方法以及使用这些化合物的方法，单独或与其他治疗剂联合使用，用于抑制细胞粘附、治疗血管生成障碍、炎症、骨质破坏、癌转移、糖尿病视网膜病变、血栓形成、再狭窄、黄斑变性和其他通过细胞粘附和/或细胞迁移和/或血管生成介导的病症。
• US5760028A
  申请人：——

  公开号：US5760028A

  公开（公告）日：1998-06-02
• Disubstituted Indazoles as Potent Antagonists of the Integrin α_vβ₃
  作者：Douglas G. Batt、Joseph J. Petraitis、Gregory C. Houghton、Dilip P. Modi、Gary A. Cain、Martha H. Corjay、Shaker A. Mousa、Peter J. Bouchard、Mark S. Forsythe、Patricia P. Harlow、Frank A. Barbera、Susan M. Spitz、Ruth R. Wexler、Prabhakar K. Jadhav

  DOI：10.1021/jm990049j

  日期：2000.1.1

  A new series of indazole-containing alpha(v)beta(3) integrin antagonists is described. Starting with lead compound 18a, variations in a number of structural features were explored with respect to inhibition of the binding of beta(3)-transfected 293 cells to fibrinogen and to selectivity for alpha(v)beta(3) over GPIIbIIIa, another RGD-binding integrin. Indazoles attached to a 2-aminopyridine or 2-aminoimidazole by a propylene linker at the indazole 1-position and to a diaminopropionate derivative via a 5-carboxylate amide provided the best potency with moderate selectivity. Several differences in the SAR of the diaminopropionate moiety were observed between this series and a series of isoxazoline-based selective GPIIbIIIa antagonists. Compound 34a (SM256) was a potent antagonist of alpha(v)beta(3) (IC50 2.3 nM) with 9-fold selectivity over GPIIbIIIa.