(3-bromo-phenyl)-(2,10-dioxa-6-thia-14,16-diaza-tricyclo[9.8.0.0(13,18)]nonadeca-1(11),12,14,16,18-pentaen-17-yl)-amine

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: (3-bromo-phenyl)-(2,10-dioxa-6-thia-14,16-diaza-tricyclo[9.8.0.0(13,18)]nonadeca-1(11),12,14,16,18-pentaen-17-yl)-amine
• 英文别名: N-(3-bromophenyl)-2,10-dioxa-6-thia-14,16-diazatricyclo[9.8.0.013,18]nonadeca-1(11),12,14,16,18-pentaen-17-amine
• 化学式: C₂₀H₂₀BrN₃O₂S
• 分子量: 446.368
• InChiKey: UAUYDWVTYSZYGT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.2
• 重原子数：
  27
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  81.6
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (3-bromo-phenyl)-(2,10-dioxa-6-thia-14,16-diaza-tricyclo[9.8.0.0(13,18)]nonadeca-1(11),12,14,16,18-pentaen-17-yl)-amine 在 Oxone 作用下， 以 甲醇 、 水 为溶剂， 反应 4.0h， 以42%的产率得到(3-bromo-phenyl)-(6,6-dioxo-2,10-dioxa-6-thia-14,16-diaza-tricyclo[9.8.0.0(13,18)]nonadeca-1(11),12,14,16,18-pentaen-17-yl)-amine
  参考文献：
  名称：

  [EN] NOVEL FUSED QUINAZOLINE DERIVATIVES USEFUL AS TYROSINE KINASE INHIBITORS
  [FR] NOUVEAUX DERIVES HYBRIDES DE QUINAZOLINE UTILES EN TANT QU'INHIBITEURS DE TYROSINE KINASE

  摘要：

  具有以下结构和式（I）的新型融合喹唑啉化合物，以及用于治疗酪氨酸激酶介导的疾病的药物组合物和使用方法。

  公开号：

  WO2003082830A1
• 作为产物：
  描述：

  4-[(3-溴苯基)氨基]-6,7-二甲氧基喹啉 在 三溴化硼 、 potassium carbonate 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 生成 (3-bromo-phenyl)-(2,10-dioxa-6-thia-14,16-diaza-tricyclo[9.8.0.0(13,18)]nonadeca-1(11),12,14,16,18-pentaen-17-yl)-amine
  参考文献：
  名称：

  冠状醚稠合喹唑啉类似物作为强效EGFR抑制剂的合成及生物学评价

  摘要：

  冠醚融合的苯胺基喹唑啉类似物被合成为新型表皮生长因子受体（EGFR）酪氨酸激酶抑制剂。代表性化合物在体外EGFR激酶测定和EGFR介导的细胞内酪氨酸磷酸化测定中显示出有效和选择性的EGFR抑制活性。报道了这些稠合的喹唑啉化合物的合成以及初步的生物学，物理和药代动力学评估。

  DOI：

  10.1016/j.bmcl.2012.06.067

文献信息

• Novel fused quinazoline derivatives useful as tyrosine kinase inhibitors
  申请人：——

  公开号：US20040048883A1

  公开（公告）日：2004-03-11

  The present invention is directed to a compound having the structure 1 wherein A is a 7-18 membered ring that comprises 0 to 6 heteroatoms selected from O, S, and N; R 1 is selected from the group consisting of hydrogen, halogen, substituted or unsubstituted C 1-8 alkyl, substituted or unsubstituted C 2-8 alkenyl, substituted or unsubstituted C 2-8 alkynyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, and substituted or unsubstituted heterocyclyl; m is an integer from 0 to 3; X is selected from the group consisting of NR 2 , CHR 3 , O, or S; wherein R 2 and R 3 are each individually H or C 1-8 alkyl; R is selected from the group consisting of unsubstituted aryl, and substituted or unsubstituted heteroaryl, substituted or unsubstituted aryl-(C 1-3 )alkyl, substituted or unsubstituted aryl-(C 3-7 )cycloalkyl, substituted or unsubstituted heteroaryl-(C 1-3 )alkyl, and substituted or unsubstituted heteroaryl-(C 3-7 )cycloalkyl; and pharmaceutically acceptable salts thereof; with the proviso that if A is a 7 or 8 membered ring, then R 1 is selected from the group consisting of other than H, C 1 -C 4 alkyl, (C 1 -C 4 alkoxy)C 1 -C 4 alkyl, C 1 -C 4 alkanoyl, C 1 -C 4 alkoxy or —S(O) x (C 1 -C 4 alkyl) wherein x is 0 to 2, and wherein said alkyl group and the alkyl moieties of said R 1 groups are optionally substituted by 1 to 3 halogens. The present invention is also directed to pharmaceutical compositions comprising the above compound, and methods of treating patients suffering from tyrosine kinase-mediated disorders using the above compound.

  本发明涉及一种具有以下结构的化合物1，其中A是一个由0到6个选自O、S和N的杂原子组成的7-18元环；R1选自氢、卤素、取代或未取代的C1-8烷基、取代或未取代的C2-8烯基、取代或未取代的C2-8炔基、取代或未取代的芳基、取代或未取代的杂芳基和取代或未取代的杂环基；m是0到3的整数；X选自NR2、CHR3、O或S；其中R2和R3各自独立地选自H或C1-8烷基；R选自未取代的芳基和取代或未取代的杂芳基、取代或未取代的芳基-(C1-3)烷基、取代或未取代的芳基-(C3-7)环烷基、取代或未取代的杂芳基-(C1-3)烷基和取代或未取代的杂芳基-(C3-7)环烷基；以及其药学上可接受的盐；但前提是如果A是一个7或8元环，则R1选自不包括H、C1-C4烷基、(C1-C4烷氧基)C1-C4烷基、C1-C4酰基、C1-C4烷氧基或—S(O)x(C1-C4烷基)，其中x为0到2，且所述烷基和所述R1基的烷基部分可以选自1到3个卤素替代。本发明还涉及包含上述化合物的制药组合物以及使用上述化合物治疗酪氨酸激酶介导的疾病的患者的方法。
• Fused quinazoline derivatives useful as tyrosine kinase inhibitors
  申请人：Beta Pharma, Inc.

  公开号：US07078409B2

  公开（公告）日：2006-07-18

  The present invention is directed to a compound having the structure wherein A is a 7–18 membered ring that comprises 0 to 6 heteroatoms selected from O, S, and N; R1 is selected from the group consisting of hydrogen, halogen, substituted or unsubstituted C1-8alkyl, substituted or unsubstituted C2-8alkenyl, substituted or unsubstituted C2-8alkynyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, and substituted or unsubstituted heterocyclyl; m is an integer from 0 to 3; X is selected from the group consisting of NR2, CHR3, O, or S; wherein R2 and R3 are each individually H or C1-8alkyl; R is selected from the group consisting of unsubstituted aryl, and substituted or unsubstituted heteroaryl, substituted or unsubstituted aryl-(C1-3)alkyl, substituted or unsubstituted aryl-(C3-7)cycloalkyl, substituted or unsubstituted heteroaryl-(C1-3)alkyl, and substituted or unsubstituted heteroaryl-(C3-7)cycloalkyl; and pharmaceutically acceptable salts thereof; with the proviso that if A is a 7 or 8 membered ring, then R1 is selected from the group consisting of other than H, C1–C4 alkyl, (C1–C4 alkoxy)C1–C4 alkyl, C1–C4 alkanoyl, C1–C4 alkoxy or —S(O)x(C1–C4 alkyl) wherein x is 0 to 2, and wherein said alkyl group and the alkyl moieties of said R1 groups are optionally substituted by 1 to 3 halogens. The present invention is also directed to pharmaceutical compositions comprising the above compound, and methods of treating patients suffering from tyrosine kinase-mediated disorders using the above compound.

  本发明涉及一种化合物，其结构为：其中A是由0到6个来自O、S和N的杂原子组成的7-18个成员环；R1选择自羟基、卤素、取代或未取代的C1-8烷基、取代或未取代的C2-8烯基、取代或未取代的C2-8炔基、取代或未取代的芳基、取代或未取代的杂芳基和取代或未取代的杂环基的群；m是0到3的整数；X选择自NR2、CHR3、O或S；其中R2和R3各自单独选择自H或C1-8烷基；R选择自未取代的芳基和取代或未取代的杂芳基、取代或未取代的芳基-(C1-3)烷基、取代或未取代的芳基-(C3-7)环烷基、取代或未取代的杂芳基-(C1-3)烷基和取代或未取代的杂芳基-(C3-7)环烷基；以及其药学上可接受的盐；但是，如果A是7或8个成员环，则R1选择自C1-C4烷基、(C1-C4烷氧基)C1-C4烷基、C1-C4烷酰基、C1-C4烷氧基或-S(O)x(C1-C4烷基)，其中x为0到2，且所述烷基和所述R1基团的烷基部分可以选择性地被1到3个卤素取代。本发明还涉及包含上述化合物的药物组合物以及使用上述化合物治疗酪氨酸激酶介导的疾病的患者的方法。
• US7078409B2
  申请人：——

  公开号：US7078409B2

  公开（公告）日：2006-07-18
• Synthesis and biological evaluation of crown ether fused quinazoline analogues as potent EGFR inhibitors
  作者：Shaojing Hu、Guojian Xie、Don X. Zhang、Charles Davis、Wei Long、Yunyan Hu、Fei Wang、Xinshan Kang、Fenlai Tan、Lieming Ding、Yinxiang Wang

  DOI：10.1016/j.bmcl.2012.06.067

  日期：2012.10

  Crown ether fused anilinoquinazoline analogues were synthesized as novel epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors. Representative compounds showed potent and selective EGFR inhibitory activities in an in vitro EGFR kinase assay and an EGFR-mediated intracellular tyrosine phosphorylation assay. The synthesis and preliminary biological, physical, and pharmacokinetic evaluation

  冠醚融合的苯胺基喹唑啉类似物被合成为新型表皮生长因子受体（EGFR）酪氨酸激酶抑制剂。代表性化合物在体外EGFR激酶测定和EGFR介导的细胞内酪氨酸磷酸化测定中显示出有效和选择性的EGFR抑制活性。报道了这些稠合的喹唑啉化合物的合成以及初步的生物学，物理和药代动力学评估。
• [EN] NOVEL FUSED QUINAZOLINE DERIVATIVES USEFUL AS TYROSINE KINASE INHIBITORS<br/>[FR] NOUVEAUX DERIVES HYBRIDES DE QUINAZOLINE UTILES EN TANT QU'INHIBITEURS DE TYROSINE KINASE
  申请人：BETA PHARMA INC

  公开号：WO2003082830A1

  公开（公告）日：2003-10-09

  Novel fused quinazoline compound having the structure, formula (I) pharmaceutical composition and method of use for treating tyrosine kinase-mediated disorders.

  具有以下结构和式（I）的新型融合喹唑啉化合物，以及用于治疗酪氨酸激酶介导的疾病的药物组合物和使用方法。