1H-1,2,3-Triazole-4-carboxamide, 5-amino-1-(4-fluorophenyl)-

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 1H-1,2,3-Triazole-4-carboxamide, 5-amino-1-(4-fluorophenyl)-
• 英文别名: 5-amino-1-(4-fluorophenyl)triazole-4-carboxamide
• 化学式: C₉H₈FN₅O
• mdl: MFCD04206862
• 分子量: 221.194
• InChiKey: QMJUTLYVBPCPJS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  99.8
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  1H-1,2,3-Triazole-4-carboxamide, 5-amino-1-(4-fluorophenyl)- 在 三氯氧磷 作用下， 以 乙腈 为溶剂， 生成
  参考文献：
  名称：

  Design and synthesis of a novel class of carbonic anhydrase-IX inhibitor 1-(3-(phenyl/4-fluorophenyl)-7-imino-3H-[1,2,3]triazolo[4,5d]pyrimidin 6(7H)yl)urea

  摘要：

  Carbonic anhydrase IX (CAIX) is a promising target in cancer therapy especially in the case of hypoxia-induced tumors. The selective inhibition of CA isozymes is a challenging task in drug design and discovery process. Here, we performed fluorescence-binding studies and inhibition assay combined with molecular docking and molecular dynamics (MD) simulation analyses to determine the binding affinity of two synthesized triazolo-pyrimidine urea derived (TPUI and TPUII) compounds with CAIX and CAN. Fluorescence binding results are showing that molecule TPUI has an excellent binding-affinity for CAIX (k(D) = 0.048 mu M). The TPUII also exhibits an appreciable binding affinity (k(D) = 7.521 mu M) for CAIX. TPUI selectively inhibits CAIX as compared to TPUII in the 4-NPA assay. Docking studies show that TPUI is spatially well-fitted in the active site cavity of CAIX, and is involve in H-bond interactions with His94, His96, His119, Thr199 and Thr200. MD simulation studies revealed that TPUI efficiently binds to CAIX and essential active site residual interaction is consistent during the entire simulation of 40 ns. These studies suggest that TPUI appeared as novel class of CAIX inhibitor, and may be used as a lead molecule for the development of potent and selective CAIX inhibitor for the hypoxia-induced cancer therapy. (C) 2016 Elsevier Inc. All rights reserved.

  DOI：

  10.1016/j.jmgm.2016.01.006
• 作为产物：
  描述：

  4-氟苯胺 在 盐酸 、 sodium azide 、 sodium nitrite 作用下， 以 乙醇 、 水 为溶剂， 生成 1H-1,2,3-Triazole-4-carboxamide, 5-amino-1-(4-fluorophenyl)-
  参考文献：
  名称：

  Design and synthesis of a novel class of carbonic anhydrase-IX inhibitor 1-(3-(phenyl/4-fluorophenyl)-7-imino-3H-[1,2,3]triazolo[4,5d]pyrimidin 6(7H)yl)urea

  摘要：

  Carbonic anhydrase IX (CAIX) is a promising target in cancer therapy especially in the case of hypoxia-induced tumors. The selective inhibition of CA isozymes is a challenging task in drug design and discovery process. Here, we performed fluorescence-binding studies and inhibition assay combined with molecular docking and molecular dynamics (MD) simulation analyses to determine the binding affinity of two synthesized triazolo-pyrimidine urea derived (TPUI and TPUII) compounds with CAIX and CAN. Fluorescence binding results are showing that molecule TPUI has an excellent binding-affinity for CAIX (k(D) = 0.048 mu M). The TPUII also exhibits an appreciable binding affinity (k(D) = 7.521 mu M) for CAIX. TPUI selectively inhibits CAIX as compared to TPUII in the 4-NPA assay. Docking studies show that TPUI is spatially well-fitted in the active site cavity of CAIX, and is involve in H-bond interactions with His94, His96, His119, Thr199 and Thr200. MD simulation studies revealed that TPUI efficiently binds to CAIX and essential active site residual interaction is consistent during the entire simulation of 40 ns. These studies suggest that TPUI appeared as novel class of CAIX inhibitor, and may be used as a lead molecule for the development of potent and selective CAIX inhibitor for the hypoxia-induced cancer therapy. (C) 2016 Elsevier Inc. All rights reserved.

  DOI：

  10.1016/j.jmgm.2016.01.006