1-[3-(1,3-Dioxo-1,3-dihydro-isoindol-2-yl)-propyl]-1H-indazole-4-carboxylic acid methyl ester | 1026183-97-0

• 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: 1-[3-(1,3-Dioxo-1,3-dihydro-isoindol-2-yl)-propyl]-1H-indazole-4-carboxylic acid methyl ester
• 英文别名: Methyl 1-[3-(1,3-dioxoisoindol-2-yl)propyl]indazole-4-carboxylate
• CAS: 1026183-97-0
• 化学式: C₂₀H₁₇N₃O₄
• 分子量: 363.373
• InChiKey: SJELNWUYTIQJNX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  27
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.2
• 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：

  1-[3-(1,3-Dioxo-1,3-dihydro-isoindol-2-yl)-propyl]-1H-indazole-4-carboxylic acid methyl ester 在 肼 作用下， 以 四氢呋喃 、 乙醇 为溶剂， 反应 16.0h， 生成 Methyl 1-(3-aminopropyl)indazole-4-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
• 作为产物：
  描述：

  3-氨基-2-甲基苯甲酸甲酯 在 盐酸 、 ammonium tetrafluoroborate 、 18-冠醚-6 、 双(三甲基硅烷基)氨基钾 、 sodium nitrite 作用下， 以 甲苯 为溶剂， 反应 52.17h， 生成 1-[3-(1,3-Dioxo-1,3-dihydro-isoindol-2-yl)-propyl]-1H-indazole-4-carboxylic acid methyl ester
  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