7-hydroxy-6-methoxyquinazoline | 916606-81-0

• 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-hydroxy-6-methoxyquinazoline
• 英文别名: 6-methoxyquinazolin-7-ol
• CAS: 916606-81-0
• 化学式: C₉H₈N₂O₂
• 分子量: 176.175
• InChiKey: VYUXQFTUJSPCEU-UHFFFAOYSA-N

物化性质

• 沸点：
  345.9±22.0 °C(Predicted)
• 密度：
  1.330±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  13
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  55.2
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  7-hydroxy-6-methoxyquinazoline 在 过氧乙酸 、 硫酸 作用下， 以 乙醇 为溶剂， 反应 12.0h， 以96%的产率得到6-甲氧基-7-羟基喹唑啉-4-酮
  参考文献：
  名称：

  Facile and Efficient Oxidation of Quinazolines into Quinazolin-4(3H)-ones by Peracetic Acid

  摘要：

  A new approach to synthesize quinazoline-4(3H)-ones was achieved by oxidation of quinazolines using peracetic acid, which possesses some advantages of economic reagents, simplified operation, high efficiency, and environmental friendliness. Application of this method allowed us to synthesize a series of quinazolin-4(3H)-ones with different substituents at 6 and 7 positions in good to excellent yields, including the key intermediates of tyrosine kinase inhibitors such as PD153035, Erlotinib, and Gefitinib. [Supplementary materials are available for this article. Go to the publisher's online edition of Synthetic Communications (R) for the following free supplemental resource(s): Full experimental and spectral details.]

  DOI：

  10.1080/00397911.2013.805230
• 作为产物：
  描述：

  6,7-二甲氧基喹唑啉 在 L-蛋氨酸 作用下， 以 甲烷磺酸 为溶剂， 反应 45.0h， 以57%的产率得到7-hydroxy-6-methoxyquinazoline
  参考文献：
  名称：

  Use of Structure-Based Design to Discover a Potent, Selective, In Vivo Active Phosphodiesterase 10A Inhibitor Lead Series for the Treatment of Schizophrenia

  摘要：

  Utilizing structure-based virtual library design and scoring, a novel chimeric series of phosphodiesterase 10A (PDE10A) inhibitors was discovered by synergizing binding site interactions and ADME properties of two chemotypes. Virtual libraries were docked and scored for potential binding ability, followed by visual inspection to prioritize analogs for parallel and directed synthesis. The process yielded highly potent and selective compounds such as 16. New X-ray cocrystal structures enabled rational design of substituents that resulted in the successful optimization of physical properties to produce in vivo activity and to modulate microsomal clearance and permeability.

  DOI：

  10.1021/jm2001508

文献信息

• Quinazoline derivatives and pharmaceutical compositions containing them
  申请人：ZENECA LIMITED

  公开号：US20020173646A1

  公开（公告）日：2002-11-21

  The invention relates to quinazoline derivatives of formula (I) wherein m is an integer from 1 to 2; R 1 represents hydrogen, hydroxy, halogeno, nitro, trifluoromethyl, cyano, C 1-13 alkyl, C 1-3 alkoxy, C 1-3 alkylthio, or —NR 5 R 6 (wherein R 5 and R 6 , which may be the same or different, each represents hydrogen or C 1-3 alkyl); R 2 represents hydrogen, hydroxy, halogeno, methoxy, amino or nitro; R 3 represents hydroxy, halogeno, C 1-3 alkyl, C 1-3 alkoxy, C 1-3 alkanoyloxy, trifluoromethyl, cyano, amino or nitro; X 1 represents —O—, —CH 2 —, —S—, —SO—, —SO 2 —, —NR 7 CO—, —CONR 8 —, —SO 2 NR 9 —-, —NR 10 SO 2 — or —NR 11 — (wherein R 7 , R 8 , R 9 , R 10 and R 11 each independently represents hydrogen, C 1-3 alkyl or C 1-3 alkoxyC 2-3 alkyl); R 4 represents an optionally substituted 5 or 6 membered saturated carbocyclic or heterocyclic group or a group which is alkenyl, alkynyl or optionally substituted alkyl, which alkyl group may contain a heteroatom linking group, which alkenyl, alkynyl or alkyl group may carry a terminal optionally substituted group selected from alkyl and a 5 or 6 membered saturated carbocyclic or heterocyclic group, and salts thereof; processes for their preparation, pharmaceutical compositions containing a compound of formula (I) or a pharmaceutically acceptable salt thereof as active ingredient. The compounds of formula (I) and the pharmaceutically acceptable salts thereof inhibit the effects of VEGF, a property of value in the treatment of a number of disease states including cancer and rheumatoid arthritis.

  本发明涉及式（I）的喹唑啉衍生物，其中m是1至2的整数；R1代表氢、羟基、卤素、硝基、三氟甲基、氰基、C1-13烷基、C1-3烷氧基、C1-3烷基硫基，或—NR5R6（其中R5和R6，可以相同也可以不同，分别代表氢或C1-3烷基）；R2代表氢、羟基、卤素、甲氧基、氨基或硝基；R3代表羟基、卤素、C1-3烷基、C1-3烷氧基、C1-3烷酰氧基、三氟甲基、氰基、氨基或硝基；X1代表—O—、—CH2—、—S—、—SO—、—SO2—、—NR7CO—、—CONR8—、—SO2NR9—、—NR10SO2—或—NR11—（其中R7、R8、R9、R10和R11各自独立地代表氢、C1-3烷基或C1-3烷氧基C2-3烷基）；R4代表一个可选取代的5或6成员饱和碳环或杂环基团或烯基、炔基或可选取代的烷基，其中烷基基团可以包含一个杂原子连接基团，烯基、炔基或烷基基团可以携带一个末端可选取代的基团，所述基团选自烷基和一个5或6成员饱和碳环或杂环基团，以及其盐；制备它们的方法，含有式（I）的化合物或其药学上可接受的盐作为活性成分的制药组合物。式（I）的化合物和药学上可接受的盐抑制VEGF的作用，这是治疗包括癌症和类风湿性关节炎在内的多种疾病状态的有价值的特性。
• 4-heterocyclyl-substituted quinazoline derivatives, processes for their
  申请人：Pfizer Inc.

  公开号：US05736534A1

  公开（公告）日：1998-04-07

  This invention relates to certain 4-aminoquinazolines and the pharmaceutically acceptable salts and stereoisomers thereof, the formula whereof are described herein. The compounds are useful for the treatment of hyperproliferative diseases, particularly as anti-cancer agents.

  本发明涉及某些4-氨基喹唑啉及其药学上可接受的盐和立体异构体，其化学式如下所述。这些化合物对于治疗增殖过度性疾病，特别是作为抗癌药物，具有用途。
• Quinazoline Derivatives, Process for Their Preparation and Their Use as Anti-Cancer Agents
  申请人：Aquila Brian

  公开号：US20080306096A1

  公开（公告）日：2008-12-11

  The invention relates to chemical compounds of the formula (I) or pharmaceutically acceptable salts thereof, which possess B Raf inhibitory activity and are accordingly useful for their anti cancer activity and thus in methods of treatment of the human or animal body. The invention also relates to processes for the manufacture of said chemical compounds, to pharmaceutical compositions containing them and to their use in the manufacture of medicaments of use in the production of an anti-cancer effect in a warm blooded animal such as man.

  本发明涉及化学式(I)或其药学上可接受的盐的化合物，其具有B Raf抑制活性，因此在抗癌活性及人或动物体的治疗方法中有用。本发明还涉及制造上述化学物质的过程，包含它们的制药组合物以及它们在制造用于在温血动物（如人）中产生抗癌效果的药物中的使用。
• Receptor-Type Kinase Modulators and Methods of Use
  申请人：SYMPHONY EVOLUTION, INC.

  公开号：US20140155418A1

  公开（公告）日：2014-06-05

  The present invention provides compounds for modulating receptor kinase activity, particularly ephrin and EGFR, and methods of treating diseases mediated by receptor kinase activity utilizing the compounds and pharmaceutical compositions thereof. Diseases mediated by receptor kinase activity include, but are not limited to, diseases characterized in part by abnormal levels of cell proliferation (i.e. tumor growth), programmed cell death (apoptosis), cell migration and invasion and angiogenesis associated with tumor growth. Compounds of the invention include “spectrum selective” kinase modulators, compounds that inhibit, regulate and/or modulate signal transduction across subfamilies of receptor-type tyrosine kinases, including ephrin and EGFR.

  本发明提供了用于调节受体激酶活性的化合物，特别是ephrin和EGFR，并利用这些化合物和其制备的药物组合物治疗受受体激酶活性介导的疾病的方法。由受体激酶活性介导的疾病包括但不限于部分由细胞增殖异常水平（即肿瘤生长）、程序性细胞死亡（凋亡）、细胞迁移和侵袭以及与肿瘤生长相关的血管生成所特征化的疾病。本发明的化合物包括“光谱选择性”激酶调节剂，抑制、调节和/或调节受体型酪氨酸激酶亚家族的信号转导，包括ephrin和EGFR。
• Processes for the preparation of substituted quinazolines
  申请人：Symphony Evolution, Inc.

  公开号：US09163006B2

  公开（公告）日：2015-10-20

  The present disclosure provides compounds for modulating receptor kinase activity, particularly ephrin and EGFR, and methods of treating diseases mediated by receptor kinase activity utilizing the compounds and pharmaceutical compositions thereof. The compounds are generally of formula (I): Diseases mediated by receptor kinase activity include, but are not limited to, diseases characterized in part by abnormal levels of cell proliferation (i.e. tumor growth), programmed cell death (apoptosis), cell migration and invasion and angiogenesis associated with tumor growth. Compounds of the invention include “spectrum selective” kinase modulators, compounds that inhibit, regulate and/or modulate signal transduction across subfamilies of receptor-type tyrosine kinases, including ephrin and EGFR. Also disclosed are methods of making compounds for formula 8: comprising introducing group E2 into a compound of formula 7: wherein Ar, Z, P, and E2 are defined herein.

  本公开提供用于调节受体激酶活性的化合物，特别是ephrin和EGFR，并利用这些化合物和其药物组合物治疗受受体激酶活性介导的疾病的方法。这些化合物通常具有式（I）：受受体激酶活性介导的疾病包括但不限于疾病的特征部分为细胞增殖异常（即肿瘤生长）、程序性细胞死亡（凋亡）、细胞迁移和侵袭以及与肿瘤生长相关的血管生成。本发明的化合物包括“光谱选择性”激酶调节剂，这些化合物抑制、调节和/或调节受体型酪氨酸激酶亚家族之间的信号转导，包括ephrin和EGFR。还公开了制备式8化合物的方法：包括将E2基团引入式7化合物中：其中Ar、Z、P和E2在此处定义。