7-(benzyloxy)-4-(methylsulfanyl)quinazoline | 220896-04-8

• 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: 7-(benzyloxy)-4-(methylsulfanyl)quinazoline
• 英文别名: 7-benzyloxy-4-methylthioquinazolin；7-benzyloxy-4-methylthioquinazoline；7-benzyloxy-4-methylsulphanylquinazoline；4-methylsulfanyl-7-phenylmethoxyquinazoline
• CAS: 220896-04-8
• 化学式: C₁₆H₁₄N₂OS
• 分子量: 282.366
• InChiKey: SHLXXALLALWYPM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  20
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  60.3
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  7-(benzyloxy)-4-(methylsulfanyl)quinazoline 在 三苯基膦 、 三氟乙酸 、 偶氮二甲酸二乙酯 作用下， 以 二氯甲烷 为溶剂， 反应 6.0h， 生成 4-(methylsulfanyl)-7-(3-morpholinopropoxy)quinazoline
  参考文献：
  名称：

  Discovery of a New Class of Anilinoquinazoline Inhibitors with High Affinity and Specificity for the Tyrosine Kinase Domain of c-Src

  摘要：

  Deregulated activity of the nonreceptor tyrosine kinase c-Src is believed to result in signal transduction, cytoskeletal and adhesion changes, ultimately promoting a tumor-invasive phenotype. We report here the discovery of a new class of anilinoquinazoline inhibitors with high affinity and specificity for the tyrosine kinase domain of the c-Src enzyme. Special attention was directed toward finding inhibitors selective against KDR tyrosine kinase in order to ensure that the in vivo profile of a specific Src inhibitor could be determined. The 4-aminobenzodioxole quinazoline series gave compounds with excellent potency and selectivity. The most interesting compounds were evaluated in vivo and displayed good pharmacokinetics following oral dosing. Compounds such as the aminobenzodioxoles were shown to be potent inhibitors of tumor growth in a c-Src-transformed 3T3 xenograft model in vivo, resulting in more than 90% growth inhibition at doses as low as 6 mg/kg po once daily. Src tyrosine kinase inhibitors such as these may provide a novel therapeutic modality for targeting cancer invasion and metastasis.

  DOI：

  10.1021/jm030317k
• 作为产物：
  描述：

  7-苄氧基-3,4-二氢喹唑啉-4-酮 在 吡啶 、 sodium hydroxide 、 tetraphosphorus decasulfide 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 8.5h， 生成 7-(benzyloxy)-4-(methylsulfanyl)quinazoline
  参考文献：
  名称：

  Discovery of a New Class of Anilinoquinazoline Inhibitors with High Affinity and Specificity for the Tyrosine Kinase Domain of c-Src

  摘要：

  Deregulated activity of the nonreceptor tyrosine kinase c-Src is believed to result in signal transduction, cytoskeletal and adhesion changes, ultimately promoting a tumor-invasive phenotype. We report here the discovery of a new class of anilinoquinazoline inhibitors with high affinity and specificity for the tyrosine kinase domain of the c-Src enzyme. Special attention was directed toward finding inhibitors selective against KDR tyrosine kinase in order to ensure that the in vivo profile of a specific Src inhibitor could be determined. The 4-aminobenzodioxole quinazoline series gave compounds with excellent potency and selectivity. The most interesting compounds were evaluated in vivo and displayed good pharmacokinetics following oral dosing. Compounds such as the aminobenzodioxoles were shown to be potent inhibitors of tumor growth in a c-Src-transformed 3T3 xenograft model in vivo, resulting in more than 90% growth inhibition at doses as low as 6 mg/kg po once daily. Src tyrosine kinase inhibitors such as these may provide a novel therapeutic modality for targeting cancer invasion and metastasis.

  DOI：

  10.1021/jm030317k

文献信息

• Therapy
  申请人：——

  公开号：US20030225111A1

  公开（公告）日：2003-12-04

  The invention concerns the use of a quinazoline derivative of Formula (I) wherein Q 1 includes a quinazoline ring optionally substituted with a group such as halogeno, trifluoromethyl and cyano, or a group of the formula: Q 3 —X 1 — wherein X 1 includes a direct bond and O and Q 3 includes aryl, aryl-(1-6C)alkyl, heterocyclyl and heterocyclyl-(1-6C)alkyl; each of R 2 and R 3 is hydrogen or (1-6C)alkyl; Z includes O, S and NH; and Q 2 includes aryl and aryl-(1-3C)alkyl or a pharmaceutically-acceptable salt thereof, in the manufacture of a medicament for use in the production of an antiangiogenic and/or vascular permeability reducing effect in a warm-blooded animal such as a human. 1

  该发明涉及使用式（I）的喹唑啉衍生物，其中Q1包括一个喹唑啉环，可选地取代为卤、三氟甲基和氰等基团，或者具有式Q3-X1-的基团，其中X1包括直接键和O，Q3包括芳基、芳基-(1-6C)烷基、杂环基和杂环基-(1-6C)烷基；R2和R3中的每一个是氢或(1-6C)烷基；Z包括O、S和NH；Q2包括芳基和芳基-(1-3C)烷基或其药用可接受盐，在制备药物时用于在温血动物（如人类）中产生抗血管生成和/或降低血管通透性的效果。
• Oxindolylquinazoline derivatives as angiogenesis inhibitors
  申请人：Zeneca Limited

  公开号：US06294532B1

  公开（公告）日：2001-09-25

  The invention relates to compounds of formula (I) and salts thereof as further defined herein, wherein ring Z is a 6-membered heterocyclic ring containing 1 to 3 nitrogen atoms, and the use of such compounds and salts to inhibit the effects of VEGF and FGF, and in the treatment of a number of disease states including cancer and rheumatoid arthritis.

  该发明涉及公式（I）的化合物及其盐，如本文所进一步定义的，其中环Z是含有1至3个氮原子的6元杂环环，以及利用这些化合物和盐来抑制VEGF和FGF的作用，并用于治疗包括癌症和类风湿性关节炎在内的多种疾病状态。
• Quinazoline derivatives
  申请人：AstraZeneca UK Limited

  公开号：US06806274B1

  公开（公告）日：2004-10-19

  The invention concerns quinazoline derivatives of Formula (I) wherein Q1 includes a quinazoline ring optionally substituted with a group such as halogeno, trifluoromethyl and cyano, or a group of the formula: Q3—X1— wherein X1 includes a direct bond and O and Q3 includes aryl, aryl-(1-6C)alkyl, heterocyclyl and heterocyclyl-(1-6C)alkyl; each of R2 and R3 is hydrogen or (1-6C)alkyl; Z includes O, S and NH; and Q2 includes aryl and aryl-(1-3C)alkyl or a pharmaceutically-acceptable salt thereof; processes for their preparation, pharmaceutical compositions containing them and their use in the manufacture of a medicament for use in the prevention or treatment of T cell mediated diseases or medical conditions in a warm-blooded animal.

  该发明涉及式(I)的喹唑啉衍生物，其中Q1包括一个喹唑啉环，可选择地取代为卤素、三氟甲基和氰基等基团，或者具有以下式的基团：Q3—X1—，其中X1包括直接键和O，Q3包括芳基、芳基-(1-6C)烷基、杂环基和杂环基-(1-6C)烷基；R2和R3中的每一个是氢或(1-6C)烷基；Z包括O、S和NH；Q2包括芳基和芳基-(1-3C)烷基或其药用可接受盐；它们的制备方法，含有它们的药物组合物以及它们在制造用于预防或治疗温血动物T细胞介导疾病或医疗状况的药物中的用途。
• OXINDOLYLQUINAZOLINE DERIVATIVES AS ANGIOGENESIS INHIBITORS
  申请人：ZENECA LIMITED

  公开号：EP1005470A1

  公开（公告）日：2000-06-07
• QUINAZOLINE DERIVATIVES
  申请人：AstraZeneca UK Limited

  公开号：EP1218353A1

  公开（公告）日：2002-07-03