4-(3-chloro-4-fluoro-phenylamino)-6,7-dihydroxy-quinazoline | 610798-32-8

• 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: 4-(3-chloro-4-fluoro-phenylamino)-6,7-dihydroxy-quinazoline
• 英文别名: 4-(3-chloro-4-fluoro-anilino)quinazoline-6,7-diol；4-((3-chloro-4-fluorophenyl)amino)quinazoline-6,7-diol；4-(3-Chloro-4-fluoroanilino)quinazoline-6,7-diol
• CAS: 610798-32-8
• 化学式: C₁₄H₉ClFN₃O₂
• 分子量: 305.696
• InChiKey: PBVZDQBUCSAPFK-UHFFFAOYSA-N

物化性质

• 沸点：
  503.2±50.0 °C(Predicted)
• 密度：
  1.616±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  21
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  78.3
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  4-(3-chloro-4-fluoro-phenylamino)-6,7-dihydroxy-quinazoline 在 potassium carbonate 、 三乙胺 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 12.0h， 生成 (4-((3-chloro-4-fluorophenyl)amino)-7,8-dihydro-[1,4]dioxino[2,3-g]quinazolin-7-yl)methanol
  参考文献：
  名称：

  Novel Quinazoline Derivative Induces Differentiation of Keratinocytes and Enhances Skin Barrier Functions against Th2 Cytokine-Mediated Signaling

  摘要：

  特应性皮炎（AD）是一种常见的炎症性皮肤病，以瘙痒性皮损和皮肤屏障功能障碍为特征。在这项研究中，我们评估了喹唑啉衍生物 SH-340 对人原代角质形成细胞中 TSLP 表达和信号转导的影响。我们的结果表明，SH-340 能显著增加分化和皮肤屏障功能因子，包括 KRT1、KRT2、KRT10、IVL、LOR、CLDN1、OVOL1 和 FLG，而它能以剂量依赖的方式在 mRNA 和蛋白质水平上抑制 TSLP 的表达。此外，SH-340 还能抑制 STAT6（IL-4 和 IL-13 的下游信号分子）在角质形成细胞中的磷酸化。这些发现表明，SH-340 可通过抑制 IL-4/IL-13-STAT6 信号通路来抑制 TSLP 的表达。最后，SH-340 可能有助于缓解炎症和恢复皮肤屏障功能。

  DOI：

  10.3390/molecules28166119
• 作为产物：
  描述：

  N-(3-chloro-4-fluorophenyl)-6,7-dimethoxyquinazolin-4-amine 在 三溴化硼 作用下， 以 四氢呋喃 为溶剂， 以63%的产率得到4-(3-chloro-4-fluoro-phenylamino)-6,7-dihydroxy-quinazoline
  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

• QUINAZOLINE DERIVATIVES AND QUINAZOLINE COMPLEX PROTEIN KINASE INHIBITOR FOR INHIBITING MULTIPLICAITON OF TUMOR CELLS AND PREPARATION METHOD THEREOF
  申请人：Wang Fuyi

  公开号：US20130225811A1

  公开（公告）日：2013-08-29

  Quinazoline derivatives represented by general formula (1) and quinazoline complexes as protein kinase inhibitors, and their preparation methods are provided. Wherein, in general formula (1), at least one of R and R′ is a group containing an atom capable of coordinating with noble metals, m and n are either the same or different and are integers from 0 to 5. Said quinazoline complex as protein kinase inhibitor is formed by coordination compound containing noble metal and said quinazoline derivative ligand capable of coordinating with noble metal in the coordination compound. Used as tyrosine protein kinase inhibitors, Quinazoline derivatives and quinazoline complexes as protein kinase inhibitors provided by the present invention have exhibited good inhibitory effect on proliferation of various tumor cells including human breast cancer cells line (drug-resistant) MCF-7/A, human breast cancer cell line (sensitive) MCF-7/S, prostate cancer cell PC-3, keratinocytes Colo-16, human non-small cell lung cancer cell line A549, etc.

  通用公式（1）表示的喹唑啉衍生物和作为蛋白激酶抑制剂的喹唑啉配合物，以及它们的制备方法已提供。在通用公式（1）中，R和R′中至少一个是含有能够与贵金属配位的原子的基团，m和n可以相同也可以不同，是从0到5的整数。所述的作为蛋白激酶抑制剂的喹唑啉配合物是由含有贵金属的配合物和所述喹唑啉衍生物配体在配合物中能够与贵金属配位而形成的。作为酪氨酸蛋白激酶抑制剂使用，本发明提供的喹唑啉衍生物和作为蛋白激酶抑制剂的喹唑啉配合物在抑制包括人类乳腺癌细胞系（耐药性）MCF-7/A、人类乳腺癌细胞系（敏感性）MCF-7/S、前列腺癌细胞PC-3、角质细胞Colo-16、人类非小细胞肺癌细胞系A549等各种肿瘤细胞增殖方面表现出良好的抑制作用。
• [EN] NOVEL FLUORINATED DERIVATIVES AS EGFR INHIBITORS USEFUL FOR TREATING CANCERS<br/>[FR] NOUVEAUX DÉRIVÉS FLUORÉS UTILISÉS EN TANT QU'INHIBITEURS D'EGFR UTILES POUR LE TRAITEMENT DE CANCERS
  申请人：TRILLIUM THERAPEUTICS INC

  公开号：WO2016123706A1

  公开（公告）日：2016-08-11

  A novel class of fluorinated derivatives of Formula I have been prepared and found to be useful in the treatment of cancers and other EGFR related disorders.

  一类新型的Formula I的氟化衍生物已经被制备出来，并发现在治疗癌症和其他与EGFR相关的疾病方面非常有用。
• [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。
• 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。
• QUINAZOLINE DERIVATIVE AND QUINAZOLINE COMPLEX PROTEIN KINASE INHIBITOR FOR INHIBITING MULTIPLICATION OF TUMOR CELLS AND PREPARATION METHOD THEREOF
  申请人：Institute Of Chemistry, Chinese Academy Of Sciences

  公开号：EP2634178A1

  公开（公告）日：2013-09-04

  Quinazoline derivatives represented by general formula (1) and quinazoline complexes as protein kinase inhibitors, and their preparation methods are provided. Wherein, in general formula (1), at least one of R and R' is a group containing an atom capable of coordinating with noble metals, m and n are either the same or different and are integers from 0 to 5. Said quinazoline complex as protein kinase inhibitor is formed by coordination compound containing noble metal and said quinazoline derivative ligand capable of coordinating with noble metal in the coordination compound. Used as tyrosine protein kinase inhibitors, Quinazoline derivatives and quinazoline complexes as protein kinase inhibitors provided by the present invention have exhibited good inhibitory effect on proliferation of various tumor cells including human breast cancer cells line (drug-resistant) MCF-7/A, human breast cancer cell line (sensitive) MCF-7/S, prostate cancer cell PC-3, keratinocytes Colo-16, human non-small cell lung cancer cell line A549, etc.

  提供了通式（1）代表的喹唑啉衍生物和作为蛋白激酶抑制剂的喹唑啉复合物及其制备方法。其中，在通式（1）中，R 和 R' 至少有一个是含有能与贵金属配位的原子的基团，m 和 n 可以相同或不同，并且是 0 至 5 的整数。作为蛋白激酶抑制剂的喹唑啉复合物是由含有贵金属的配位化合物和配位化合物中能与贵金属配位的喹唑啉衍生物配体形成的。作为酪氨酸蛋白激酶抑制剂，本发明提供的喹唑啉衍生物和喹唑啉复合物作为蛋白激酶抑制剂，对多种肿瘤细胞的增殖具有良好的抑制作用，包括人乳腺癌细胞株（耐药）MCF-7/A、人乳腺癌细胞株（敏感）MCF-7/S、前列腺癌细胞PC-3、角质形成细胞Colo-16、人非小细胞肺癌细胞株A549等。