tert-butyl 3-(1-(2-chlorophenyl)-3-(2-methoxy-2-oxoethyl)-5-oxo-1,5-dihydro-4H-pyrazol-4-ylidene)-1,4-diazepane-1-carboxylate | 1350522-90-5

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮
• 英文名称: tert-butyl 3-(1-(2-chlorophenyl)-3-(2-methoxy-2-oxoethyl)-5-oxo-1,5-dihydro-4H-pyrazol-4-ylidene)-1,4-diazepane-1-carboxylate
• CAS: 1350522-90-5
• 化学式: C₂₂H₂₇ClN₄O₅
• 分子量: 462.933
• InChiKey: OOSGUFHTBGKRNL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.09
• 重原子数：
  32.0
• 可旋转键数：
  3.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  100.54
• 氢给体数：
  1.0
• 氢受体数：
  7.0

反应信息

• 作为反应物：
  描述：

  tert-butyl 3-(1-(2-chlorophenyl)-3-(2-methoxy-2-oxoethyl)-5-oxo-1,5-dihydro-4H-pyrazol-4-ylidene)-1,4-diazepane-1-carboxylate 在 sodium methylate 作用下， 以 甲醇 为溶剂， 反应 0.5h， 以33%的产率得到tert-butyl 2-(2-chlorophenyl)-1,5-dioxo-2,3,5,8,9,11-hexahydro-1H-pyrazolo[4',3':3,4]pyrido[1,2-a][1,4]diazepine-10(7H)-carboxylate
  参考文献：
  名称：

  Design, synthesis and biological activity of original pyrazolo-pyrido-diazepine, -pyrazine and -oxazine dione derivatives as novel dual Nox4/Nox1 inhibitors

  摘要：

  Pyrazolo-pyrido-diazepine, -pyrazine and -oxazine dione derivatives are new chemical entities with good and attractive druglikeness properties. A series of pyrazolo-pyrido-diazepine dione analogs demonstrated to be particularly amenable to lead optimization through a couple of cycles in order to improve specificity for isoforms Nox4 and Nox1 and had excellent pharmacokinetic parameters by oral route. Several molecules such as compound 7c proved to be highly potent in in vitro assays on human lung fibroblasts differentiation as well as in curative murine models of bleomycin-induced pulmonary fibrosis with superior efficiency over Pirfenidone. Pyrazolo-pyrido-diazepine dione derivatives targeting Nox4 and Nox1 isoforms appear highly promising therapeutics for the treatment of idiopathic pulmonary fibrosis. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2011.10.016
• 作为产物：
  描述：

  methyl [4-(chloroacetyl)-1-(2-chlorophenyl)-5-hydroxy-1H-pyrazol-3-yl]acetate 在 碳酸氢钠 作用下， 以 1,4-二氧六环 、 乙腈 为溶剂， 反应 1.0h， 生成 tert-butyl 3-(1-(2-chlorophenyl)-3-(2-methoxy-2-oxoethyl)-5-oxo-1,5-dihydro-4H-pyrazol-4-ylidene)-1,4-diazepane-1-carboxylate
  参考文献：
  名称：

  Design, synthesis and biological activity of original pyrazolo-pyrido-diazepine, -pyrazine and -oxazine dione derivatives as novel dual Nox4/Nox1 inhibitors

  摘要：

  Pyrazolo-pyrido-diazepine, -pyrazine and -oxazine dione derivatives are new chemical entities with good and attractive druglikeness properties. A series of pyrazolo-pyrido-diazepine dione analogs demonstrated to be particularly amenable to lead optimization through a couple of cycles in order to improve specificity for isoforms Nox4 and Nox1 and had excellent pharmacokinetic parameters by oral route. Several molecules such as compound 7c proved to be highly potent in in vitro assays on human lung fibroblasts differentiation as well as in curative murine models of bleomycin-induced pulmonary fibrosis with superior efficiency over Pirfenidone. Pyrazolo-pyrido-diazepine dione derivatives targeting Nox4 and Nox1 isoforms appear highly promising therapeutics for the treatment of idiopathic pulmonary fibrosis. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2011.10.016