4-[(4-fluoro-3-methylphenyl)amino]-6-[3-(morpholin-4-yl)propyloxy]-7-methoxyquinazoline

• 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-[(4-fluoro-3-methylphenyl)amino]-6-[3-(morpholin-4-yl)propyloxy]-7-methoxyquinazoline
• 英文别名: N-(4-fluoro-3-methylphenyl)-7-methoxy-6-(3-morpholin-4-ylpropoxy)quinazolin-4-amine
• 化学式: C₂₃H₂₇FN₄O₃
• 分子量: 426.491
• InChiKey: HSPYFUDFYBJASI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  31
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  68.7
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  4-[(4-fluoro-3-methylphenyl)amino]-6-[3-(morpholin-4-yl)propyloxy]-7-methoxyquinazoline 、 丙烯酰氯 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 8.0h， 以33%的产率得到4-[N-acryloyl-(4-fluoro-3-methylphenyl)amino]-6-[3-(morpholin-4-yl)propyloxy]-7-methoxyquinazoline
  参考文献：
  名称：

  Acrylamide Functional Group Incorporation Improves Drug-like Properties: An Example with EGFR Inhibitors

  摘要：

  We demonstrate that the acrylamide group can be used to improve the drug-like properties of potential drug candidates. In the EGFR inhibitor development, both the solubility and membrane permeability properties of compounds 6a and 7, each containing an acrylamide group, were substantially better than those of gefitinib (1) and AZD3759 (2), respectively. We demonstrated that incorporation of an acrylamide moiety could serve as a good strategy for improving drug-like properties.

  DOI：

  10.1021/acsmedchemlett.8b00270
• 作为产物：
  描述：

  7-甲氧基-6-(3-吗啉-4-基丙氧基)喹唑啉-4(3H)-酮 在 溶剂黄146 、 三乙胺 、 三氯氧磷 作用下， 反应 10.0h， 生成 4-[(4-fluoro-3-methylphenyl)amino]-6-[3-(morpholin-4-yl)propyloxy]-7-methoxyquinazoline
  参考文献：
  名称：

  Acrylamide Functional Group Incorporation Improves Drug-like Properties: An Example with EGFR Inhibitors

  摘要：

  We demonstrate that the acrylamide group can be used to improve the drug-like properties of potential drug candidates. In the EGFR inhibitor development, both the solubility and membrane permeability properties of compounds 6a and 7, each containing an acrylamide group, were substantially better than those of gefitinib (1) and AZD3759 (2), respectively. We demonstrated that incorporation of an acrylamide moiety could serve as a good strategy for improving drug-like properties.

  DOI：

  10.1021/acsmedchemlett.8b00270

文献信息

• COMPOUNDS TARGETING PROTEINS, COMPOSITIONS, METHODS, AND USES THEREOF
  申请人：BioTheryX, Inc.

  公开号：US20180170948A1

  公开（公告）日：2018-06-21

  The present invention provides compounds that modulate protein function, to restore protein homeostasis, including cytokine, CK1α, GSPT1, aiolos, and/or ikaros activity, and cell-cell adhesion. The invention provides methods of modulating protein-mediated diseases, such as cytokine-mediated diseases, disorders, conditions, or responses. Compositions, including in combination with other cytokine and inflammatory mediators, are provided. Methods of treatment, amelioration, or prevention of diseases, disorders, or conditions associated with a protein, such as diseases, disorders, and conditions associated with cytokines, including inflammation, fibromyalgia, rheumatoid arthritis, osteoarthritis, ankylosing spondylitis, psoriasis, psoriatic arthritis, inflammatory bowel diseases, Crohn's disease, ulcerative colitis, uveitis, inflammatory lung diseases, chronic obstructive pulmonary disease, Alzheimer's disease, and cancer, are provided.

  本发明提供了调节蛋白功能的化合物，以恢复蛋白稳态，包括细胞因子、CK1α、GSPT1、艾奥洛斯和/或伊卡洛斯活性和细胞间粘附。该发明提供了一种调节蛋白介导的疾病的方法，如细胞因子介导的疾病、障碍、状况或反应。提供了包括与其他细胞因子和炎症介质结合的组合物。提供了治疗、改善或预防与蛋白相关的疾病、障碍或状况的方法，包括与细胞因子相关的疾病、障碍和状况，包括炎症、纤维肌痛、类风湿性关节炎、骨关节炎、强直性脊柱炎、银屑病、银屑病关节炎、炎症性肠病、克罗恩病、溃疡性结肠炎、葡萄膜炎、炎症性肺病、慢性阻塞性肺病、阿尔茨海默病和癌症。
• QUINAZOLINE BASED EGFR INHIBITORS CONTAINING A ZINC BINDING MOIETY
  申请人：Qian Changgeng

  公开号：US20080139590A1

  公开（公告）日：2008-06-12

  The present invention relates to quinazoline containing zinc-binding moiety based derivatives that have enhanced and unexpected properties as inhibitors of epidermal growth factor receptor tyrosine kinase (EGFR-TK) and their use in the treatment of EGFR-TK related diseases and disorders such as cancer. The said derivatives may further act as HDAC inhibitors.

  本发明涉及含有锌结合基团的喹唑啉衍生物，其具有增强和意外的性质，作为表皮生长因子受体酪氨酸激酶（EGFR-TK）抑制剂，并用于治疗EGFR-TK相关的疾病和疾病，如癌症。所述衍生物还可以作为HDAC抑制剂。
• TARTRATE SALTS OF QUINAZOLINE BASED EGFR INHIBITORS CONTAINING A ZINC BINDING MOIETY
  申请人：Cai Xiong

  公开号：US20110053963A1

  公开（公告）日：2011-03-03

  The present invention relates to tartrate salts of quinazoline containing zinc-binding moiety based derivatives of Formula II, below. These compounds are inhibitors of epidermal growth factor receptor tyrosine kinase (EGFR-TK) and may further act as HDAC inhibitors. The invention further relates to the use of these tartrate salts in the treatment of EGFR-TK related diseases and disorders such as cancer.

  本发明涉及以下公式II的基于含锌结合基的衍生物的喹嗪酸盐，这些化合物是表皮生长因子受体酪氨酸激酶（EGFR-TK）的抑制剂，可能进一步作为HDAC抑制剂。本发明还涉及在治疗EGFR-TK相关疾病和疾病，如癌症中使用这些酒石酸盐的用途。
• PYRIDAZINONES AND FURAN-CONTAINING COMPOUNDS
  申请人：Djaballah Hakim

  公开号：US20100210649A1

  公开（公告）日：2010-08-19

  The present invention is directed to pyridazinone compounds of formula (I) and furan compounds of formula (II), pharmaceutical compositions of compounds of formula (I) and (II), kits containing these compounds, methods of syntheses, and a method of treatment of a proliferative disease in a subject by administration of a therapeutically effective amount of a compound of formulae (I) or (II). Both classes of compounds were identified through screening of a collection of small molecule libraries.

  本发明涉及式(I)的吡啶二酮化合物和式(II)的呋喃化合物，以及式(I)和(II)化合物的制药组合物、包含这些化合物的试剂盒、合成方法，以及通过给予式(I)或(II)化合物的治疗有效量来治疗受体内增生性疾病的方法。这两类化合物是通过筛选小分子库的集合而确定的。
• PRODRUG FORMS OF KINASE INHIBITORS AND THEIR USE IN THERAPY
  申请人：Smaill Jeffrey Bruce

  公开号：US20120077811A1

  公开（公告）日：2012-03-29

  The invention provides novel prodrug compounds comprising a kinase inhibitor and a reductively-activated fragmenting aromatic nitroheterocycle or aromatic nitrocarbocycle trigger, where the compound carries a positive charge. In preferred embodiments, the compounds are of Formula I: where: X is any negatively charged counterion; R 1 is a group of the formula —(CH 2 ) n Tr, where Tr is an aromatic nitroheterocycle or aromatic nitrocarbocycle and —(CH 2 ) n Tr acts as a reductively-activated fragmenting trigger; and n is an integer from 0 to 6; R 2 , R 3 and R 4 may each independently be selected from aliphatic or aromatic groups of a tertiary amine kinase inhibitor (R 2 )(R 3 )(R 4 )N, or two of R 2 , R 3 , and R 4 may form an aliphatic or aromatic heterocyclic amine ring of a kinase inhibitor, or one of R 2 , R 3 and R 4 may be absent and two of R 2 , R 3 and R 4 form an aromatic heterocyclic amine ring of a kinase inhibitor. The compounds of the invention are useful in treating proliferative diseases such as cancer.

  本发明提供了新型的前药化合物，包括一种激酶抑制剂和一种还原活化的破裂芳香族硝基杂环或芳香族硝基碳杂环触发剂，其中该化合物带有正电荷。在优选实施例中，该化合物为式I：其中：X是任何带负电的反离子；R1是公式—(CH2)nTr的基团，其中Tr是芳香族硝基杂环或芳香族硝基碳杂环，—(CH2)nTr作为还原活化的破裂触发器；n是0到6的整数；R2、R3和R4可以各自独立地选择来自三级胺激酶抑制剂的脂肪族或芳香族基团(R2)(R3)(R4)N，或者R2、R3和R4中的两个可以形成激酶抑制剂的脂肪族或芳香族杂环胺环，或者R2、R3和R4中的一个可以缺失，R2、R3和R4中的两个可以形成激酶抑制剂的芳香族杂环胺环。该发明的化合物可用于治疗增殖性疾病，如癌症。