(S)-2-Benzyloxycarbonylamino-3-({1-[3-(1-trityl-1H-imidazol-2-ylamino)-propyl]-1H-indazole-5-carbonyl}-amino)-propionic acid tert-butyl ester | 257293-60-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 三苯基化合物
• 英文名称: (S)-2-Benzyloxycarbonylamino-3-({1-[3-(1-trityl-1H-imidazol-2-ylamino)-propyl]-1H-indazole-5-carbonyl}-amino)-propionic acid tert-butyl ester
• CAS: 257293-60-0
• 化学式: C₄₈H₄₉N₇O₅
• 分子量: 803.961
• InChiKey: VCGDNSBHWREMKF-RWYGWLOXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.94
• 重原子数：
  60.0
• 可旋转键数：
  16.0
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  141.4
• 氢给体数：
  3.0
• 氢受体数：
  10.0

反应信息

• 作为反应物：
  描述：

  (S)-2-Benzyloxycarbonylamino-3-({1-[3-(1-trityl-1H-imidazol-2-ylamino)-propyl]-1H-indazole-5-carbonyl}-amino)-propionic acid tert-butyl ester 在 10percent Pd/C 吡啶 、 4-二甲氨基吡啶 、 氢气 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 23.0h， 生成 (S)-2-(Toluene-4-sulfonylamino)-3-({1-[3-(1-trityl-1H-imidazol-2-ylamino)-propyl]-1H-indazole-5-carbonyl}-amino)-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 (S)-2-Benzyloxycarbonylamino-3-({1-[3-(1-trityl-1H-imidazol-2-ylamino)-propyl]-1H-indazole-5-carbonyl}-amino)-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