tert-Butyl 3-[1-[3-(N-(1-triphenylmethylimidazol-2-yl)-amino)propyl]-indazol-5-ylcarbonylamino]-2(S)-(2,4,6-trimethylbenzenesulfonylamino)propionate | 192944-46-0

• 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-[3-(N-(1-triphenylmethylimidazol-2-yl)-amino)propyl]-indazol-5-ylcarbonylamino]-2(S)-(2,4,6-trimethylbenzenesulfonylamino)propionate
• 英文别名: tert-butyl (2S)-2-[(2,4,6-trimethylphenyl)sulfonylamino]-3-[[1-[3-[(1-tritylimidazol-2-yl)amino]propyl]indazole-5-carbonyl]amino]propanoate
• CAS: 192944-46-0
• 化学式: C₄₉H₅₃N₇O₅S
• 分子量: 852.07
• InChiKey: WYIWXBKIHOJBQM-WBCKFURZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  8.7
• 重原子数：
  62
• 可旋转键数：
  18
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  158
• 氢给体数：
  3
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  tert-Butyl 3-[1-[3-(N-(1-triphenylmethylimidazol-2-yl)-amino)propyl]-indazol-5-ylcarbonylamino]-2(S)-(2,4,6-trimethylbenzenesulfonylamino)propionate 在 溶剂黄146 作用下， 以 甲醇 为溶剂， 以81%的产率得到(S)-3-({1-[3-(1H-Imidazol-2-ylamino)-propyl]-1H-indazole-5-carbonyl}-amino)-2-(2,4,6-trimethyl-benzenesulfonylamino)-propionic acid tert-butyl 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
• 作为产物：
  描述：

  ethyl 1-[2-(1,3-dioxolan-2-yl)ethyl]indazole-5-carboxylate 在 sodium hydroxide 、 三乙酰氧基硼氢化钠 、 1-羟基苯并三唑 、 溶剂黄146 、 N,N'-二环己基碳二亚胺 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 88.0h， 生成 tert-Butyl 3-[1-[3-(N-(1-triphenylmethylimidazol-2-yl)-amino)propyl]-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