1-(2-羧乙基)吲唑-5-羧酸乙酯 | 192945-43-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并吡唑类
• 中文名称: 1-(2-羧乙基)吲唑-5-羧酸乙酯
• 英文名称: ethyl 1-(2-carboxyethyl)indazole-5-carboxylate
• 英文别名: 1-(2-Carboxyethyl)-5-ethoxycarbonylindazole；3-(5-Ethoxycarbonylindazol-1-yl)propanoic acid
• CAS: 192945-43-0
• 化学式: C₁₃H₁₄N₂O₄
• 分子量: 262.265
• InChiKey: DYTRFXIMNSSDMI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  19
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  81.4
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  1-(2-羧乙基)吲唑-5-羧酸乙酯 在 lithium hydroxide 、 (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 为溶剂， 反应 57.0h， 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
• 作为产物：
  描述：

  1H-吲唑-5-甲酸乙酯 在 lithium hydroxide 、 potassium tert-butylate 作用下， 以 四氢呋喃 、 叔丁醇 为溶剂， 反应 0.75h， 生成 1-(2-羧乙基)吲唑-5-羧酸乙酯
  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 antagonists
  申请人：——

  公开号：US20010044535A1

  公开（公告）日：2001-11-22

  This invention relates to novel heterocycles which are useful as antagonists of the &agr; v &bgr; 3 integrin, the &agr; 2b &bgr; 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.

  这项发明涉及一种新颖的杂环化合物，可用作αvβ3整合素、α2bβ3整合素以及相关细胞表面粘附蛋白受体的拮抗剂，还涉及含有这些化合物的药物组合物、制备这些化合物的方法，以及使用这些化合物单独或与其他治疗剂联合用于抑制细胞粘附、治疗血管生成障碍、炎症、骨降解、癌症转移、糖尿病性视网膜病变、血栓形成、再狭窄、黄斑变性以及其他通过细胞粘附和/或细胞迁移和/或血管生成介导的疾病的方法。
• PYRIMIDINES AND TRIAZINES AS INTEGRIN ANTAGONISTS
  申请人：Du Pont Pharmaceuticals Company

  公开号：EP1054871A2

  公开（公告）日：2000-11-29
• US5760028A
  申请人：——

  公开号：US5760028A

  公开（公告）日：1998-06-02
• US6489333B2
  申请人：——

  公开号：US6489333B2

  公开（公告）日：2002-12-03
• [EN] INTEGRIN ANTAGONISTS<br/>[FR] ANTAGONISTES DE L'INTEGRINE
  申请人：——

  公开号：WO1999050249A2

  公开（公告）日：1999-10-07

  [EN] This invention relates to novel heterocycles which are useful as antagonists of the alpha v beta 3 integrin, the alpha 2b beta 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.
  [FR] Cette invention, qui a trait à de nouveaux composés hétérocycliques se révélant des plus utiles en tant qu'antagonistes de l'intégrine alpha v beta 3, de l'intégrine alpha 2b beta 3 et de récepteurs de protéines adhérant à la surface cellulaire connexes, concerne également des compositions pharmaceutiques renfermant ces composés, des procédés de production de ces composés ainsi que des méthodes d'utilisation desdits composés, seuls ou associés à d'autres agents thérapeutiques, aux fins de l'inhibition de l'adhésion cellulaire, du traitement de troubles angiogéniques, d'inflammations, de la dégénérescence osseuse, de la métastase cancéreuse, de la rétinopathie diabétique, de la thrombose, de la resténose, de la dégénérescence maculaire et d'autres états pathologiques provoqués par une adhésion cellulaire et/ou une migration cellulaire et/ou l'angiogenèse.