(2R)-7-(2-hydroxy-3-(pyrrolidin-1-yl)propoxy)-4-(4-fluoro-2-methylindol-5-yloxy)-6methoxyquinazoline | 288383-25-5

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: (2R)-7-(2-hydroxy-3-(pyrrolidin-1-yl)propoxy)-4-(4-fluoro-2-methylindol-5-yloxy)-6methoxyquinazoline
• 英文别名: (2R)-7-(2-hydroxy-3-(pyrrolidin-1-yl)propoxy)-4-(4-fluoro-2-methylindol-5-yloxy)-6-methoxyquinazoline；(2R)-1-[4-[(4-fluoro-2-methyl-1H-indol-5-yl)oxy]-6-methoxyquinazolin-7-yl]oxy-3-pyrrolidin-1-ylpropan-2-ol
• CAS: 288383-25-5
• 化学式: C₂₅H₂₇FN₄O₄
• 分子量: 466.512
• InChiKey: GCABIYVOJWRUBO-MRXNPFEDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  34
• 可旋转键数：
  8
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  92.7
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  (2R)-7-(2-acetoxy-3-(pyrrolidin-1-yl)propoxy)-4-(4-fluoro-2-methylindol-5-yloxy)-6-methoxyquinazoline 、 氨 在 methanol-dichloromethane 、 氨 作用下， 以 甲醇 为溶剂， 反应 16.0h， 以to give (2R)-7-(2-hydroxy-3-(pyrrolidin-1-yl)propoxy)-4-(4-fluoro-2-methylindol-5-yloxy)-6-methoxyquinazoline (390 mg; 75%)的产率得到(2R)-7-(2-hydroxy-3-(pyrrolidin-1-yl)propoxy)-4-(4-fluoro-2-methylindol-5-yloxy)-6methoxyquinazoline
  参考文献：
  名称：

  Quinazoline derivatives as angiogenesis inhibitors

  摘要：

  本发明涉及使用公式（I）的化合物，其中环C是一个包含1-3个独立选择的杂原子O、N和S的8、9、10、12或13元双环或三环基团；Z是-O-、-NH-、-S-、-CH2-或直接键；n为0-5；m为0-3；R2表示氢、羟基、卤代、氰基、硝基、三氟甲基、C1-3烷基、C1-3烷氧基、C1-3烷基硫基、-NR3R4（其中R3和R4，可以相同，也可以不同，分别表示氢或C1-3烷基），或R5Xt-（其中X1和R5如上定义）；R1表示氢、酮、卤代、羟基、C1-4烷氧基、C1-4烷基、C1-4烷氧甲基、C1-4酰基、C1-4卤代烷基、氰基、氨基、C2-5烯基、C2-5炔基、C1-3酰氧基、硝基、C1-4酰胺基、C1-4烷氧羰基、C1-4烷基硫基、C1-4烷基亚硫基、C1-4烷基磺酰基、氨基甲酰基、N-C1-4烷基氨基甲酰基、N，N-二（C1-4烷基）氨基甲酰基、氨基磺酰基、N-C1-4烷基氨基磺酰基、N，N-二（C1-4烷基）氨基磺酰基、N-（C1-4烷基磺酰基）氨基、N-（C1-4烷基磺酰基）-N-（C1-4烷基）氨基、N，N-二（C1-4烷基磺酰基）氨基、连接两个环C碳原子的C3-7烷基链、C1-4酰胺基C1-4烷基、羧基或R56X10基团（其中X10和R56如上定义）；以及其盐，在制造用于产生在温血动物中的抗血管生成和/或血管通透性减少效应的药物中使用，制备这种化合物的方法，含有公式（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和公式（I）的化合物。公式（I）的化合物及其药学上可接受的盐抑制VEGF的效果，在治疗包括癌症和类风湿性关节炎在内的多种疾病状态中具有价值。

  公开号：

  US20060004017A1

文献信息

• Therapeutic agents comprising an anti-angiogenic agent in combination with an src-inhibitor and their therapeutic use
  申请人：Curwen Owen Jon

  公开号：US20060223815A1

  公开（公告）日：2006-10-05

  The invention relates to the use of an anti-angiogenic agent in combination with an inhibitor of the Src family of non-receptor tyrosine kinases in the manufacture of a medicament for use in the substantially normotensive treatment in a warm-blooded mammal such as a human being of a disease state associated with angiogenesis, the Src kinase inhibitor being administered in an amount effective to counteract substantially the hypertension induced by the anti-angiogenic agent.

  本发明涉及在制造一种药物时使用抗血管生成剂与Src家族非受体酪氨酸激酶抑制剂相结合，用于治疗与血管生成有关的疾病状态，如在温血哺乳动物（如人类）中进行实质性正常血压治疗。 Src激酶抑制剂的用量有效地对抗抗血管生成剂引起的高血压。
• THERAPEUTIC AGENTS COMPRISING AN ANTI-ANGIOGENIC AGENT IN COMBINATION WITH AN SRC-INHIBITOR AND THEIR THERAPEUTIC USE
  申请人：CURWEN Jon Owen

  公开号：US20100029673A1

  公开（公告）日：2010-02-04

  The invention relates to a method for the production of an anti-cancer effect or a method for the treatment of a sold tumour disease by administration of an anti-angiogenic agent selected from 4-(4-fluoro-2-methylindol-5-yloxy)-6-methoxy-7-(3-(pyrrolidin-1-yl)propoxy)quinazoline and 4-(4-bromo-2-fluoroanilino)-6-methoxy-7-(1-methylpiperidin-4-ylmethoxy)quinazoline and pharmaceutically-acceptable acid-addition salts thereof, in combination with a Src kinase inhibitor selected from 4-(6-chloro-2,3-methylenedioxyanilino)-7-[2-(4-methylpiperazin-1-yl)ethoxy]-5-tetrahydropyran-4-yloxyquinazoline and pharmaceutically-acceptable acid-addition salts thereof.

  本发明涉及一种通过给予选择自4-(4-氟-2-甲基吲哚-5-氧基)-6-甲氧基-7-(3-(吡咯烷-1-基)丙氧基)喹唑啉和4-(4-溴-2-氟苯胺基)-6-甲氧基-7-(1-甲基哌啶-4-基甲氧基)喹唑啉及其药学上可接受的酸盐，结合选择自4-(6-氯-2,3-亚甲二氧基苯胺基)-7-[2-(4-甲基哌嗪-1-基)乙氧基]-5-四氢吡喃-4-氧基喹唑啉及其药学上可接受的酸盐的Src激酶抑制剂，以产生抗癌效应或治疗固体肿瘤疾病的方法。
• Quinazoline Derivatives as Angiogenesis Inhibitors
  申请人：Stokes Elaine S.E.

  公开号：US20120197027A1

  公开（公告）日：2012-08-02

  The invention relates to the use of compounds of formula (I) and salts thereof, in the manufacture of a medicament for use in the production of an antiangiogenic and/or vascular permeability reducing effect in warm-blooded animals, processes for the preparation of such compounds, pharmaceutical compositions containing a compound of formula I or a pharmaceutically acceptable salt thereof as active ingredient and compounds of formula I. 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.

  该发明涉及使用式(I)的化合物及其盐，在制造用于在温血动物中产生抗血管生成和/或减少血管通透性效果的药物中的应用，制备这种化合物的方法，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药物组合物以及式I的化合物。式(I)的化合物及其药学上可接受的盐抑制VEGF的效果，这是在治疗包括癌症和类风湿性关节炎在内的多种疾病状态中具有价值的特性。
• Therapeutic combinations of antihypertensive and antiangiogenics agents
  申请人：——

  公开号：US20030144298A1

  公开（公告）日：2003-07-31

  The invention concerns the use of a combination of an anti-angiogenic agent and an anti-hypertensive agent for use in the manufacture of a medicament for the treatment of a disease state associated with angiogenesis in a warm-blooded mammal, such as a human being. The invention also relates to pharmaceutical compositions comprising an anti-angiogenic agent and an anti-hypertensive agent, to kits thereof and to a method of treatment of a disease state associated with angiogenesis which comprises the administration of an effective amount of a combination of an anti-angiogenic agent and an anti-hypertensive agent to a warm-blooded animal, such as a human being.

  本发明涉及使用抗血管生成抑制剂和抗高血压药物的组合制剂，用于制造治疗与血管生成有关的疾病状态的药物，适用于温血动物，如人类。本发明还涉及包含抗血管生成抑制剂和抗高血压药物的制药组合物，以及相关的工具包和治疗方法，包括向温血动物（如人类）施用有效量的抗血管生成抑制剂和抗高血压药物的组合。
• QUINAZOLINE DERIVATIVES AS ANGIOGENESIS INHIBITORS AND INTERMEDIATES THEREFORE
  申请人：AstraZeneca AB

  公开号：EP1553097A1

  公开（公告）日：2005-07-13

  The invention relates to the use of compounds of the formula I: wherein ring C is an 8, 9, 10, 12 or 13-membered bicyclic or tricyclic moiety which optionally may contain 1-3 heteroatoms selected independently from O, N and S; Z is -O-, -NH-, -S-, -CH2- or a direct bond; n is 0-5; m is 0-3; R2 represents hydrogen, hydroxy, halogeno, cyano, nitro, trifluoromethyl, C1-3alkyl, C1-3alkoxy, C1-3alkylsulphanyl, -NR3R4 (wherein R3 and R4, which may be the same or different, each represents hydrogen or C1-3alkyl), or R5X1- (wherein X1 and R5 are as defined herein; R1 represents hydrogen, oxo, halogeno, hydroxy, C1-4alkoxy, C1-4alkyl, C1-4alkoxymethyl, C1-4alkanoyl, C1-4haloalkyl, cyano, amino, C2-5alkenyl, C2-5alkynyl, C1-3alkanoyloxy, nitro, C1-4alkanoylamino, C1-4alkoxycarbonyl, C1-4alkylsulphanyl, C1-4alkylsulphinyl, C1-4alkylsulphonyl, carbamoyl, N-C1-4alkylcarbamoyl, N,N-di(C1-4alkyl)carbamoyl, aminosulphonyl, N-C1-4alkylaminosulphonyl, N,N-di(C1-4alkyl)aminosulphonyl, N-(C1-4alkylsulphonyl)amino, N-(C1-4alkylsulphonyl)-N-(C1-4alkyl)amino, N,N-di(C1-4alkylsulphonyl)amino, a C3-7alkylene chain joined to two ring C carbon atoms, C1-4alkanoylaminoC1-4alkyl, carboxy or a group R56X10 (wherein X10 and R56 are as defined herein); and salts thereof, in the manufacture of a medicament for use in the production of an antiangiogenic and/or vascular permeability reducing effect in warm-blooded animals, processes for the preparation of such compounds, pharmaceutical compositions containing a compound of formula I or a pharmaceutically acceptable salt thereof as active ingredient and compounds of formula I. 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 化合物的用途： 其中环 C 是 8、9、10、12 或 13 元双环或三环分子，可任选含有 1-3 个独立选自 O、N 和 S 的杂原子；Z 是 -O-、-NH-、-S-、-CH2- 或直接键；n 是 0-5；m 是 0-3；R2 代表氢、羟基、卤代、氰基、硝基、三氟甲基、C1-3 烷基、C1-3 烷氧基、C1-3 烷基硫代、-NR3R4（其中 R3 和 R4 可以相同或不同，各自代表氢或 C1-3 烷基）或 R5X1-（其中 X1 和 R5 如本文所定义；R1代表氢、氧代、卤代、羟基、C1-4烷氧基、C1-4烷基、C1-4烷氧基甲基、C1-4烷酰基、C1-4卤代烷基、氰基、氨基、C2-5烯基、C2-5炔基、C1-3烷酰氧基硝基、C1-4-烷酰氨基、C1-4-烷氧基羰基、C1-4-烷基硫酰基、C1-4-烷基亚砜基、C1-4-烷基磺酰基、氨基甲酰基、N-C1-4-烷基氨基甲酰基、N,N-二（C1-4-烷基）氨基甲酰基氨基磺酰基、N-C1-4烷基氨基磺酰基、N,N-二(C1-4烷基)氨基磺酰基、N-(C1-4烷基磺酰基)氨基、N-(C1-4烷基磺酰基)-N-(C1-4烷基)氨基、N,N-二(C1-4烷基磺酰基)氨基、与两个环 C 碳原子相连的 C3-7 烯链、C1-4-烷酰氨基 C1-4烷基、羧基或基团 R56X10（其中 X10 和 R56 如本文所定义）；及其盐，用于制造在温血动物中产生抗血管生成和/或降低血管通透性作用的药物、制备此类化合物的工艺、含有式 I 化合物或其药学上可接受的盐作为活性成分的药物组合物以及式 I 化合物。式 I 化合物及其药学上可接受的盐可抑制血管内皮生长因子的作用，这一特性在治疗包括癌症和类风湿性关节炎在内的多种疾病中具有重要价值。