(S)-2-tert-Butoxycarbonylamino-3-cyclohexyl-propionic acid benzotriazol-1-yl ester | 300372-32-1

• 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: (S)-2-tert-Butoxycarbonylamino-3-cyclohexyl-propionic acid benzotriazol-1-yl ester
• CAS: 300372-32-1
• 化学式: C₂₀H₂₈N₄O₄
• 分子量: 388.467
• InChiKey: DEURCZUNAHSOKS-INIZCTEOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.25
• 重原子数：
  28.0
• 可旋转键数：
  5.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  95.34
• 氢给体数：
  1.0
• 氢受体数：
  7.0

反应信息

• 作为反应物：
  描述：

  (S)-2-tert-Butoxycarbonylamino-3-cyclohexyl-propionic acid benzotriazol-1-yl ester 在 盐酸 、 PS-DIEA resin 、 戴斯-马丁氧化剂 作用下， 以 1,4-二氧六环 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 14.5h， 生成 BnSO2-D-Phe-Cha-Arg(Mtr)-thiazol-2-yl
  参考文献：
  名称：

  Polymer-Assisted Solution-Phase Library Synthesis and Crystal Structure of α-Ketothiazoles as Tissue Factor VIIa Inhibitors

  摘要：

  A solution-phase synthesis of an alpha-ketothiazole library of the general form D-Phe-L-AA-Arg-alpha-ketothiazole is described. The five-step synthesis is accomplished using a combination of polymeric reagents and polymer-assisted solution-phase purification concepts, including reactant-sequestering resins, reagent-sequestering resins, and tagged reagents. The multistep synthesis affords desired alpha-ketothiazole products in excellent purities and yields. A variety of L-amino acid inputs were used to probe the S-2 pocket of tissue Factor VIIa enzyme to influence both potency and selectivity. An X-ray crystal structure of compound 10k bound to the TF/ VIIa complex was obtained that explains the observed selectivity. The alpha-ketothiazoles were found to be potent, reversible-covalent inhibitors of tissue Factor VIIa, with some analogues demonstrating selectivity over thrombin.

  DOI：

  10.1021/jm030130t
• 作为产物：
  描述：

  丁氧羰基--环乙基-丙氨酸-羟基盐酸盐 、 1-羟基苯并三唑 在 PS-carbodiimide resin 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 0.25h， 生成 (S)-2-tert-Butoxycarbonylamino-3-cyclohexyl-propionic acid benzotriazol-1-yl ester
  参考文献：
  名称：

  Polymer-Assisted Solution-Phase Library Synthesis and Crystal Structure of α-Ketothiazoles as Tissue Factor VIIa Inhibitors

  摘要：

  A solution-phase synthesis of an alpha-ketothiazole library of the general form D-Phe-L-AA-Arg-alpha-ketothiazole is described. The five-step synthesis is accomplished using a combination of polymeric reagents and polymer-assisted solution-phase purification concepts, including reactant-sequestering resins, reagent-sequestering resins, and tagged reagents. The multistep synthesis affords desired alpha-ketothiazole products in excellent purities and yields. A variety of L-amino acid inputs were used to probe the S-2 pocket of tissue Factor VIIa enzyme to influence both potency and selectivity. An X-ray crystal structure of compound 10k bound to the TF/ VIIa complex was obtained that explains the observed selectivity. The alpha-ketothiazoles were found to be potent, reversible-covalent inhibitors of tissue Factor VIIa, with some analogues demonstrating selectivity over thrombin.

  DOI：

  10.1021/jm030130t