1-(3-methoxy-4-nitrophenyl)pyrrolidine

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯烷类
• 英文名称: 1-(3-methoxy-4-nitrophenyl)pyrrolidine
• 化学式: C₁₁H₁₄N₂O₃
• mdl: MFCD00546012
• 分子量: 222.244
• InChiKey: KTPYTBWTSLNUGL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.454
• 拓扑面积：
  58.3
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1-(3-methoxy-4-nitrophenyl)pyrrolidine 在 iron(III) chloride hexahydrate 、 甲烷 、 对甲苯磺酸 、 一水合肼 作用下， 以 乙醇 、 异丙醇 为溶剂， 反应 12.0h， 生成 8-(5-chloro-2-((2-methoxy-4-(pyrrolidin-1-yl)phenyl)amino)pyrimidin-4-yl)-1-phenyl-1,3,8-triazaspiro[4.5]decan-4-one
  参考文献：
  名称：

  Design, synthesis and biological evaluation of 2-arylaminopyrimidine derivatives bearing 1,3,8-triazaspiro[4,5]decan-4-one or piperidine-3-carboxamide moiety as novel Type-I1/2 ALK inhibitors

  摘要：

  Aiming to develop novel Type -I-1/2 inhibitors of ALK to overcome extensive resistance mutations, especially the L1196M mutation surrounding the ATP pocket, two series of 2-arylaminopyrimidine derivatives (11a-f and 22at) were designed based on scaffold hopping. The extensive structural elaboration discovered compound 22o which possessed excellent IC50 values of 0.06 and 0.23 mu M against ALK-positive Karpas299 and H2228 cell lines, respectively. Meanwhile, 22o displayed encouraging inhibitory potency in the ALK(WT) (2.5 nM) and ALK(L1196m )(6.5 nM) enzymatic assays. Furthermore, the AO/EB and Hoechst 33258 assays illustrated 22o could induce cell apoptosis in a dose-dependent manner. Eventually, the molecular docking of 22o with ALK clearly presented the vital interactions within the active site, which was in accordance with Type -I-1/2 inhibitor binding mode.

  DOI：

  10.1016/j.bioorg.2019.103456
• 作为产物：
  描述：

  四氢吡咯 、 5-氟-2-硝基苯甲醚 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 1-(3-methoxy-4-nitrophenyl)pyrrolidine
  参考文献：
  名称：

  吡唑并[1,5-a]嘧啶衍生物作为强效FLT3-ITD抑制剂的发现和结构-活性关系探索

  摘要：

  FLT3 的内部串联重复 (FLT3-ITD) 发生在大约 25% 的所有急性髓性白血病 (AML) 病例中，并且预后不良。我们内部化合物库中筛选命中1的优化导致发现了一系列吡唑并[1,5 - a ]嘧啶衍生物作为有效和选择性的 FLT3-ITD 抑制剂。化合物17和19显示出有效的 FLT3-ITD 活性，IC 50值为 0.4 nM，并且对 AML 细胞系具有优异的抗增殖活性。特别是化合物17和19抑制了 quizartinib 的耐药性—— 赋予突变FLT3 D835Y，两者都具有0.3 nM的IC 50值。此外，蛋白质印迹分析表明化合物17和19有效抑制了 FLT3 的磷酸化并减弱了 AML 细胞中的下游信号传导。这些结果表明吡唑并[1,5 - a ]嘧啶衍生物可能是治疗AML的有前途的FLT3-ITD抑制剂。

  DOI：

  10.1016/j.bmc.2021.116422

文献信息

• Discovery and structure − activity relationship exploration of pyrazolo[1,5-a]pyrimidine derivatives as potent FLT3-ITD inhibitors
  作者：Yun Chen、Gang Bai、Yan Li、Yi Ning、Sufen Cao、Jinpei Zhou、Jian Ding、Huibin Zhang、Hua Xie、Wenhu Duan

  DOI：10.1016/j.bmc.2021.116422

  日期：2021.10

  myeloid leukemia (AML) cases and confer a poor prognosis. Optimization of the screening hit 1 from our in-house compound library led to the discovery of a series of pyrazolo[1,5-a]pyrimidine derivatives as potent and selective FLT3-ITD inhibitors. Compounds 17 and 19 displayed potent FLT3-ITD activities both with IC50 values of 0.4 nM and excellent antiproliferative activities against AML cell lines. Especially

  FLT3 的内部串联重复 (FLT3-ITD) 发生在大约 25% 的所有急性髓性白血病 (AML) 病例中，并且预后不良。我们内部化合物库中筛选命中1的优化导致发现了一系列吡唑并[1,5 - a ]嘧啶衍生物作为有效和选择性的 FLT3-ITD 抑制剂。化合物17和19显示出有效的 FLT3-ITD 活性，IC 50值为 0.4 nM，并且对 AML 细胞系具有优异的抗增殖活性。特别是化合物17和19抑制了 quizartinib 的耐药性—— 赋予突变FLT3 D835Y，两者都具有0.3 nM的IC 50值。此外，蛋白质印迹分析表明化合物17和19有效抑制了 FLT3 的磷酸化并减弱了 AML 细胞中的下游信号传导。这些结果表明吡唑并[1,5 - a ]嘧啶衍生物可能是治疗AML的有前途的FLT3-ITD抑制剂。
• Aromatic sulfonamides as peroxynitrite-rearrangement catalysts
  申请人：Schering AG

  公开号：US20040204452A1

  公开（公告）日：2004-10-14

  The invention relates to the use of aromatics sulfonamides of the general formula I as peroxynitrite rearrangement catalysts, to the preparation thereof and to the use thereof as medicament for the treatment of various disorders. 1

  本发明涉及使用一般式I的芳香磺酰胺作为过氧亚硝酸重排催化剂，其制备方法和用作治疗各种疾病的药物的用途。
• US6946466B2
  申请人：——

  公开号：US6946466B2

  公开（公告）日：2005-09-20
• [EN] AROMATIC SULFONAMIDES AS PEROXYNITRITE-REARRANGEMENT CATALYSTS<br/>[FR] SULFONAMIDES AROMATIQUES CONVENANT COMME CATALYSEURS D'INTERESTERIFICATION PEROXYNITRITIQUE
  申请人：SCHERING AG

  公开号：WO2004089882A2

  公开（公告）日：2004-10-21

  The invention relates to the use of aromatics sulfonamides of the general formula (I) as peroxynitrite rearrangement catalysts, to the preparation thereof and to the use thereof as medicament for the treatment of various disorders.
• Design, synthesis and biological evaluation of 2-arylaminopyrimidine derivatives bearing 1,3,8-triazaspiro[4,5]decan-4-one or piperidine-3-carboxamide moiety as novel Type-I1/2 ALK inhibitors
  作者：Xiuqi Miao、Lingyun Xing、Ming Guo、Hong Zhang、Sicong Liu、Shiliang Yin、Ping Gong、Dajun Zhang、Xin Zhai

  DOI：10.1016/j.bioorg.2019.103456

  日期：2020.1

  Aiming to develop novel Type -I-1/2 inhibitors of ALK to overcome extensive resistance mutations, especially the L1196M mutation surrounding the ATP pocket, two series of 2-arylaminopyrimidine derivatives (11a-f and 22at) were designed based on scaffold hopping. The extensive structural elaboration discovered compound 22o which possessed excellent IC50 values of 0.06 and 0.23 mu M against ALK-positive Karpas299 and H2228 cell lines, respectively. Meanwhile, 22o displayed encouraging inhibitory potency in the ALK(WT) (2.5 nM) and ALK(L1196m )(6.5 nM) enzymatic assays. Furthermore, the AO/EB and Hoechst 33258 assays illustrated 22o could induce cell apoptosis in a dose-dependent manner. Eventually, the molecular docking of 22o with ALK clearly presented the vital interactions within the active site, which was in accordance with Type -I-1/2 inhibitor binding mode.