ethyl 2-(3-[1-phthalimido]propyl)indazole-5-carboxylate | 192944-61-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异吲哚及其衍生物
• 英文名称: ethyl 2-(3-[1-phthalimido]propyl)indazole-5-carboxylate
• 英文别名: Ethyl 2-[3-(1,3-dioxoisoindol-2-yl)propyl]indazole-5-carboxylate
• CAS: 192944-61-9
• 化学式: C₂₁H₁₉N₃O₄
• 分子量: 377.4
• InChiKey: FDFDKXMQCPDANS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  28
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  81.5
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  ethyl 2-(3-[1-phthalimido]propyl)indazole-5-carboxylate 在 肼 作用下， 以 四氢呋喃 、 乙醇 为溶剂， 反应 16.0h， 生成
  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：

  N-(3-溴丙基)苯二胺 、 1H-吲唑-5-甲酸乙酯 在 18-冠醚-6 、 双(三甲基硅烷基)氨基钾 作用下， 以 甲苯 为溶剂， 反应 16.0h， 以48%的产率得到ethyl 1-(3-[1-phthalimido]propyl)indazole-5-carboxylate
  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

• NOVEL INTEGRIN RECEPTOR ANTAGONISTS
  申请人：Dupont Pharmaceuticals Company

  公开号：EP0939757A1

  公开（公告）日：1999-09-08
• [EN] NOVEL INTEGRIN RECEPTOR ANTAGONISTS<br/>[FR] NOUVEAUX ANTAGONISTES DE RECEPTEURS D'INTEGRINES
  申请人：THE DU PONT MERCK PHARMACEUTICAL COMPANY

  公开号：WO1997023480A1

  公开（公告）日：1997-07-03

  (EN) This invention relates to novel heterocycles including 3-[1-[3-(imidazolin-2-ylamino)propyl]indazol-5-ylcarbonylamino]-2-(benzyloxycarbonylamino)propionic acid, which are useful as antagonists of the $g(a)v$g(b)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 angiongenic 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) Nouveaux hétérocycles comprenant de l'acide 3-[1-[3-(imidazolin-2-ylamino)propyl]indazol-5-ylcarbonylamino]-2-(benzyloxycarbonylamino)propionique, qui sont utiles en tant qu'antagonistes des récepteurs de l'intégrine $g(a)v$g(b)3 et de récepteurs de protéines adhésives de surface cellulaire associées, compositions pharmaceutiques contenant lesdits composés, procédés de préparation desdits composés et procédés d'utilisation desdits composés, seuls ou en combinaison avec d'autres agents thérapeutiques pour l'inhibition de l'adhésion cellulaire, le traitement des troubles angiogéniques, des inflammations, de la dégradation osseuse, des métastases cancéreuses, de la rétinopathie diabétique, de la thrombose, de la resténose, de la dégénérescence maculaire et d'autres troubles induits par l'adhésion cellulaire et/ou la migration cellulaire et/ou l'angiogenèse.
• 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.