4-[(3-溴苯基)氨基]-6,7-二乙氧基喹唑啉 | 171745-13-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 中文名称: 4-[(3-溴苯基)氨基]-6,7-二乙氧基喹唑啉
• 中文别名: N-(3-溴苯基)-6,7-二乙氧基-4-喹唑啉胺
• 英文名称: 4-(3'-bromoanilino)-6,7-diethoxyquinazoline
• 英文别名: Compound 56；4-[(3-bromophenyl)amino]-6,7-diethoxyquinazoline；(3-Bromophenyl)-(6,7-diethoxyquinazolin-4-yl)-amine；N-(3-bromophenyl)-6,7-diethoxyquinazolin-4-amine
• CAS: 171745-13-4
• 化学式: C₁₈H₁₈BrN₃O₂
• 分子量: 388.264
• InChiKey: YXOXHAUUTIOBDA-UHFFFAOYSA-N

物化性质

• 溶解度：
  不溶于水； DMSO 中≥16.95 mg/mL； ≥47.6 mg/mL，乙醇溶液（需要超声波）

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  24
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  56.3
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  4-[(3-溴苯基)氨基]-6,7-二乙氧基喹唑啉 在 四(三苯基膦)钯 六甲基二锡 、 过氧乙酸 、 sodium iodide 、 sodium acetate 作用下， 以 甲苯 、 乙腈 为溶剂， 反应 0.07h， 生成 4-(3'-[125I]iodoanilino)-6,7-diethoxyquinazoline
  参考文献：
  名称：

  Synthesis of 4-(3′-[125I]iodoanilino)-6,7-dialkoxyquinazolines: radiolabeled epidermal growth factor receptor tyrosine kinase inhibitors

  摘要：

  The preparation of two radioiodinated analogs of the epidermal growth factor receptor tyrosine kinase (EGFrTK) inhibitor PD153035 (4-(3'-bromoanilino)-6,7-dimethoxyquinazoline) are reported herein. The two analogs, 4-(3'-[I-125]iodoanilino)-6,7-dimethoxyquinazoline and 4-(3'-[I-125]iodoanilino)-6,7-diethoxyquinazoline, were synthesized via iododestannylation of the corresponding 4-(3'-trimethylstannylanilino)-6,7-dialkoxyquinazolines to form the desired I-125 labeled products in good yield, high radiochemical purity (>99%) and high specific activity.

  DOI：

  10.1002/1099-1344(20001030)43:12<1183::aid-jlcr405>3.0.co;2-n
• 作为产物：
  描述：

  4-氯-6,7-二甲氧基喹唑啉 在 吡啶盐酸盐 、 potassium carbonate 作用下， 以 二甲基亚砜 、 异丙醇 为溶剂， 反应 23.0h， 生成 4-[(3-溴苯基)氨基]-6,7-二乙氧基喹唑啉
  参考文献：
  名称：

  Tyrosine Kinase Inhibitors. 8. An Unusually Steep Structure−Activity Relationship for Analogues of 4-(3-Bromoanilino)-6,7-dimethoxyquinazoline (PD 153035), a Potent Inhibitor of the Epidermal Growth Factor Receptor

  摘要：

  4-(3-Bromoanilino)-6,7-dimethoxyquinazoline (32, PD 153035) is a very potent inhibitor (IC50 0.025 nM) of the tyrosine kinase activity of the epidermal growth factor receptor (EGFR), binding competitively at the ATP site. Structure-activity relationships for close analogues of 32 are very steep. Some derivatives have IC(50)s UP to 80-fold better than predicted from simple additive binding energy arguments, yet analogues possessing combinations of similar phenyl and quinazoline substituents do not show this ''supra-additive'' effect. Because some substituents which are mildly deactivating by themselves can be strongly activating when used in the correct combinations, it is proposed that certain substituted analogues possess the ability to induce a change in the conformation of the receptor when they bind. There is some bulk tolerance for substitution in the 6- and 7-positions of the quinazoline, so that 32 is not the optimal inhibitor for the induced conformation. The diethoxy derivative 56 [4-(3-bromoanilino)-6,7-diethoxyquinazoline] shows an IC50 Of 0.006 nM, making it the most potent inhibitor of the tyrosine kinase activity of the EGFR yet reported.

  DOI：

  10.1021/jm9503613

文献信息

• TREATMENT OF CANCERS HAVING RESISTANCE TO CHEMOTHERAPEUTIC AGENTS
  申请人：Wilhelm Scott

  公开号：US20100173954A1

  公开（公告）日：2010-07-08

  The present invention provides compositions and methods for treating cancer with DAST, 44-[3-(4-chloro-3-trifluoromethylphenyl)-ureido]-3-fluorophenoxy}-pyridine-2-carboxylic acid methylamide of the formula I, including all polymorphs, hydrates, pharmaceutically acceptable salts, metabolites, prodrugs, solvates or combinations thereof. Any cancer can be treated, including cancers that have acquired resistance to another therapeutic agent, such as kinase inhibitors. DAST can also be used to treat cancers which have become refractory to other chemotherapeutic agents

  本发明提供了使用DAST（44-[3-(4-氯-3-三氟甲基苯基)-尿素]-3-氟苯氧基}-吡啶-2-羧酸甲酰胺，I式），包括所有多晶形态、水合物、药学上可接受的盐、代谢物、前药、溶剂化合物或其组合物，治疗癌症的组合物和方法。可以治疗任何癌症，包括已经对其他治疗药物（如激酶抑制剂）产生耐药性的癌症。DAST还可用于治疗已经对其他化疗药物产生耐药性的癌症。
• Cellular kinases involved in cytomegalovirus infection and their inhibition
  申请人：Axxima Pharmaceuticals Aktiengesellschaft

  公开号：EP1201765A2

  公开（公告）日：2002-05-02

  The role of certain cellular kinases active during Human Cytomegalovirus infection is disclosed. These cellular kinases are useful to detect HCMV infection, and can be used to screen for cellular kinase inhibitors. Cellular kinases inhibitors, which effectively downregulate these key cellular components, serve as effective therapeutics against HCMV infection.

  本研究揭示了人类巨细胞病毒感染期间活跃的某些细胞激酶的作用。这些细胞激酶有助于检测 HCMV 感染，并可用于筛选细胞激酶抑制剂。细胞激酶抑制剂能有效下调这些关键细胞成分，可作为抗 HCMV 感染的有效疗法。
• Use of EGFR pathway inhibitors to increase immune responses to antigens
  申请人：Emory University

  公开号：US10034931B2

  公开（公告）日：2018-07-31

  This disclosure relates to using EGFR pathway inhibitors in combination with compositions comprising an antigen to increase, elicit, or improve an antigen or vaccine-induced immune response. In certain embodiments, the EGFR pathway inhibitor is administered under conditions such that memory cells to the antigen are formed in a subject. In certain embodiments, the composition is a vaccine. In certain embodiments, the EGFR pathway inhibitor and vaccine are administered to the skin epidermis or dermis.

  本公开涉及将表皮生长因子受体通路抑制剂与包含抗原的组合物结合使用，以增加、激发或改善抗原或疫苗诱导的免疫反应。在某些实施方案中，表皮生长因子受体通路抑制剂的给药条件是在受试者体内形成对抗原的记忆细胞。在某些实施方案中，组合物是一种疫苗。在某些实施方案中，表皮生长因子受体途径抑制剂和疫苗施用到皮肤表皮或真皮。
• Cellular kinases involved in Cytomegalovirus infection and their inhibition
  申请人：——

  公开号：US20030082519A1

  公开（公告）日：2003-05-01

  The role of certain cellular kinases active during Human Cytomegalovirus infection is disclosed. These cellular kinases are useful to detect HCMV infection, and can be used to screen for cellular kinase inhibitors. Cellular kinases inhibitors, which effectively downregulate these key cellular components, serve as effective therapeutics against HCMV infection.

  本研究揭示了人类巨细胞病毒感染期间活跃的某些细胞激酶的作用。这些细胞激酶有助于检测 HCMV 感染，并可用于筛选细胞激酶抑制剂。细胞激酶抑制剂能有效下调这些关键细胞成分，可作为抗 HCMV 感染的有效疗法。
• Antipsychotic molecular-targeting epithelial growth factor receptor
  申请人：Nawa Hiroyuki

  公开号：US20060167026A1

  公开（公告）日：2006-07-27

  The purpose of this invention is to provide an agent useful for prevention and/or treatment of psychosis, schizophrenia and cognitive impairments. To solve this problem, this invention provides epidermal growth factor receptor inhibitors as therapeutic agents for psychosis, schizophrenia and cognitive impairments.

  本发明的目的是提供一种用于预防和/或治疗精神病、精神分裂症和认知障碍的药物。为了解决这个问题，本发明提供了表皮生长因子受体抑制剂作为治疗精神病、精神分裂症和认知障碍的药物。