tert-Butyl 3-[1-[2-(N-imidazol-2ylaminocarbonyl)ethyl]indazol-5-ylcarbonylamino]-2-(S)-(2,4,6-trimethylbenzenesulfonylamino)propionate | 192945-46-3

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: tert-Butyl 3-[1-[2-(N-imidazol-2ylaminocarbonyl)ethyl]indazol-5-ylcarbonylamino]-2-(S)-(2,4,6-trimethylbenzenesulfonylamino)propionate
• 英文别名: tert-butyl (2S)-3-[[1-[3-(1H-imidazol-2-ylamino)-3-oxopropyl]indazole-5-carbonyl]amino]-2-[(2,4,6-trimethylphenyl)sulfonylamino]propanoate
• CAS: 192945-46-3
• 化学式: C₃₀H₃₇N₇O₆S
• 分子量: 623.733
• InChiKey: STBVUPNXGHSFGT-QHCPKHFHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  44
• 可旋转键数：
  13
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.37
• 拓扑面积：
  186
• 氢给体数：
  4
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  三氟乙酸 、 tert-Butyl 3-[1-[2-(N-imidazol-2ylaminocarbonyl)ethyl]indazol-5-ylcarbonylamino]-2-(S)-(2,4,6-trimethylbenzenesulfonylamino)propionate 以 二氯甲烷 为溶剂， 以31%的产率得到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 、 1-羟基苯并三唑 、 N,N-二异丙基乙胺 、 N,N'-二环己基碳二亚胺 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 、 叔丁醇 为溶剂， 反应 81.75h， 生成 tert-Butyl 3-[1-[2-(N-imidazol-2ylaminocarbonyl)ethyl]indazol-5-ylcarbonylamino]-2-(S)-(2,4,6-trimethylbenzenesulfonylamino)propionate
  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