methyl 1-[3-(4,5-dihydro-1H-imidazol-2-ylamino)propyl]indazole-6-carboxylate | 1026401-22-8

• 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: methyl 1-[3-(4,5-dihydro-1H-imidazol-2-ylamino)propyl]indazole-6-carboxylate
• CAS: 1026401-22-8
• 化学式: C₁₅H₁₉N₅O₂
• 分子量: 301.348
• InChiKey: AUWOVWITJWDBBH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.5
• 重原子数：
  22
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  80.5
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  methyl 1-[3-(4,5-dihydro-1H-imidazol-2-ylamino)propyl]indazole-6-carboxylate 在 sodium hydroxide 、 1-羟基苯并三唑 、 三乙胺 、 N,N'-二环己基碳二亚胺 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 32.0h， 生成 tert-butyl (2S)-3-[[1-[3-(4,5-dihydro-1H-imidazol-2-ylamino)propyl]indazole-6-carbonyl]amino]-2-(phenylmethoxycarbonylamino)propanoate
  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-4-甲基苯甲酸甲酯 在 吡啶 、 盐酸 、 ammonium tetrafluoroborate 、 18-冠醚-6 、 双(三甲基硅烷基)氨基钾 、 肼 、 sodium nitrite 作用下， 以 四氢呋喃 、 乙醇 、 甲苯 为溶剂， 反应 73.17h， 生成 methyl 1-[3-(4,5-dihydro-1H-imidazol-2-ylamino)propyl]indazole-6-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