[tert-Butoxycarbonylmethyl-(2-{2-[2-(4-sulfamoyl-benzoylamino)-ethoxy]-ethoxy}-ethyl)-amino]-acetic acid tert-butyl ester | 762288-82-4

• 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-Butoxycarbonylmethyl-(2-{2-[2-(4-sulfamoyl-benzoylamino)-ethoxy]-ethoxy}-ethyl)-amino]-acetic acid tert-butyl ester
• CAS: 762288-82-4
• 化学式: C₂₅H₄₁N₃O₉S
• 分子量: 559.681
• InChiKey: JBOFOKLUOFNXRK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.08
• 重原子数：
  38.0
• 可旋转键数：
  15.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.64
• 拓扑面积：
  163.56
• 氢给体数：
  2.0
• 氢受体数：
  10.0

反应信息

• 作为反应物：
  描述：

  [tert-Butoxycarbonylmethyl-(2-{2-[2-(4-sulfamoyl-benzoylamino)-ethoxy]-ethoxy}-ethyl)-amino]-acetic acid tert-butyl ester 在 盐酸 作用下， 以 1,4-二氧六环 为溶剂， 反应 5.0h， 以99%的产率得到
  参考文献：
  名称：

  Two-Prong Inhibitors for Human Carbonic Anhydrase II

  摘要：

  The enzyme inhibitors are usually designed by taking into consideration the overall dimensions of the enzyme's active site pockets. This conventional approach often fails to produce desirable affinities of inhibitors for their cognate enzymes. To circumvent such constraints, we contemplated enhancing the binding affinities of inhibitors by attaching tether groups, which would interact with the surface exposed amino acid residues. This strategy has been tested for the inhibition of human carbonic anhydrase II. Benzenesulfonamide serves as a weak inhibitor for the enzyme, but when it is conjugated to iminodiacetate-Cu2+ (which interacts with the surface-exposed His residues) via a spacer group, its binding affinity is enhanced by about 2 orders of magnitude. This "two-prong" approach is expected to serve as a general strategy for converting weak inhibitors of enzymes into tight-binding inhibitors.

  DOI：

  10.1021/ja047271k
• 作为产物：
  描述：

  对羧基苯磺酰胺 、 tert-butyl 2-(2-(2-(2-aminoethoxy)ethoxy)ethyl)((tert-butyloxycarbonyl)methylamino)acetate 在 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 、 三乙胺 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 12.0h， 以61%的产率得到[tert-Butoxycarbonylmethyl-(2-{2-[2-(4-sulfamoyl-benzoylamino)-ethoxy]-ethoxy}-ethyl)-amino]-acetic acid tert-butyl ester
  参考文献：
  名称：

  Protein Surface-Assisted Enhancement in the Binding Affinity of an Inhibitor for Recombinant Human Carbonic Anhydrase-II

  摘要：

  We elaborate on a novel strategy for enhancing the binding affinity of an active-site directed inhibitor by attaching a tether group, designed to interact with the surface-exposed histidine residue(s) of enzymes. In this approach, we have utilized the recombinant form of human carbonic anhydrase-II (hCA-II) as the enzyme source and benzenesulfonamide and its derivatives as inhibitors. The steady-state kinetic and the ligand binding data revealed that the attachment of iminodiacetate (IDA)-Cu2+ to benzenesulfonamide (via a triethylene glycol spacer) enhanced its binding affinity for hCA-II by about 40-fold. No energetic contribution of either IDA or triethylene glycol spacer was found (at least in the ground state of the enzyme-inhibitor complex) when Cu2+ was stripped off from the tether group-conjugated sulfonamide derivative. Arguments are presented that the overall strategy of enhancing the binding affinities of known inhibitors by attaching the IDA-Cu2+ groups to interact with the surface-exposed histidine residues will find a general application in designing the isozyme-specific inhibitors as potential drugs.

  DOI：

  10.1021/ja047557p