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 | 1278416-49-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 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
• 英文别名: Tert-butyl 4-(2-chlorophenyl)-3,8-dioxo-4,5,9,13-tetrazatricyclo[7.5.0.02,6]tetradeca-1,6-diene-13-carboxylate
• CAS: 1278416-49-1
• 化学式: C₂₁H₂₃ClN₄O₄
• 分子量: 430.891
• InChiKey: QAGPTTNFAWOFFR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  30
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  82.2
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  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 在 盐酸 作用下， 以 1,4-二氧六环 、 二氯甲烷 为溶剂， 反应 0.5h， 以91%的产率得到2-(2-chlorophenyl)-2,3,8,9,10,11-hexahydro-1H-pyrazolo[4',3':3,4]pyrido[1,2-a][1,4]diazepine-1,5(7H)-dione hydrochloride
  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 sodium methylate 、 碳酸氢钠 作用下， 以 1,4-二氧六环 、 甲醇 、 乙腈 为溶剂， 反应 1.5h， 生成 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

文献信息

• [EN] PYRAZOLINE DIONE DERIVATIVES AS NADPH OXIDASE INHIBITORS<br/>[FR] DÉRIVÉS DE PYRAZOLINE DIONE UTILISÉS EN TANT QU'INHIBITEURS DE NADPH OXYDASE
  申请人：GENKYOTEX SA

  公开号：WO2011036651A1

  公开（公告）日：2011-03-31

  The present invention is related to pyrazoline dione derivatives of Formula (I), pharmaceutical composition thereof and to their use for the treatment and/or prophylaxis of disorders or conditions related to Nicotinamide adenine dinucleotide phosphate oxidase (NADPH Oxidase).

  本发明涉及式（I）的吡唑烯二酮衍生物，其制药组合物以及它们用于治疗和/或预防与烟酰胺腺嘌呤二核苷酸磷酸氧化酶（NADPH氧化酶）相关的疾病或症状。
• Pyrazoline dione derivatives as nadph oxidase inhibitors
  申请人：GenKyoTex SA

  公开号：EP2305679A1

  公开（公告）日：2011-04-06

  The present invention is related to pyrazoline dione derivatives of Formula (I), pharmaceutical composition thereof and to their use for the treatment and/or prophylaxis of disorders or conditions related to Nicotinamide adenine dinucleotide phosphate oxidase (NADPH Oxidase).

  本发明涉及式(I)的吡唑烷二酮衍生物，其药物组成部分以及它们用于治疗和/或预防与尼克酰胺腺嘌呤二核苷酸磷酸酸化酶（NADPH氧化酶）相关的疾病或症状。
• PYRAZOLINE DIONE DERIVATIVES AS NADPH OXIDASE INHIBITORS
  申请人：Page Patrick

  公开号：US20120172352A1

  公开（公告）日：2012-07-05

  The present invention is related to pyrazoline dione derivatives of Formula (I), pharmaceutical composition thereof and to their use for the treatment and/or prophylaxis of disorders or conditions related to Nicotinamide adenine dinucleotide phosphate oxidase (NADPH Oxidase).

  本发明涉及式(I)的吡唑烷二酮衍生物、其制药组合物以及它们用于治疗和/或预防与尼克酰胺腺嘌呤二核苷酸磷酸酰化酶（NADPH氧化酶）相关的疾病或症状的用途。
• EP2483271B1
  申请人：——

  公开号：EP2483271B1

  公开（公告）日：2017-08-16
• US9394306B2
  申请人：——

  公开号：US9394306B2

  公开（公告）日：2016-07-19