4-chloro-6-methoxy-7-(2-(pyrrolidin-1-yl)ethoxy)quinazoline | 199327-79-2

• 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-chloro-6-methoxy-7-(2-(pyrrolidin-1-yl)ethoxy)quinazoline
• 英文别名: 4-chloro-6-methoxy-7-pyrrolidinoethoxyquinazoline；4-chloro-6-methoxy-7-(2-pyrrolidin-1-ylethoxy)quinazoline
• CAS: 199327-79-2
• 化学式: C₁₅H₁₈ClN₃O₂
• 分子量: 307.78
• InChiKey: YXCADIWEURXKPS-UHFFFAOYSA-N

物化性质

• 沸点：
  455.7±45.0 °C(Predicted)
• 密度：
  1.270±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  21
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  47.5
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  4-chloro-6-methoxy-7-(2-(pyrrolidin-1-yl)ethoxy)quinazoline 在 potassium carbonate 、 N,N-二异丙基乙胺 、 三氟乙酸 作用下， 以 二氯甲烷 、 N,N-二甲基乙酰胺 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 19.0h， 生成 N-(3-methoxyphenyl)-2-[4-[6-methoxy-7-(2-pyrrolidin-1-ylethoxy)quinazolin-4-yl]oxypyrazol-1-yl]acetamide
  参考文献：
  名称：

  Discovery of AZD2932, a new Quinazoline Ether Inhibitor with high affinity for VEGFR-2 and PDGFR tyrosine kinases

  摘要：

  A new series of Quinazoline Ether Inhibitor which potently inhibits VEGFR-2 and PDGFR tyrosine kinases is described here. In vitro, pharmacokinetics and in vivo evaluations led to the selection of AZD2932. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.11.019
• 作为产物：
  描述：

  6-methoxy-7-pyrrolidinoethoxyquinazolin-4-one 在 三氯氧磷 作用下， 反应 6.0h， 以49%的产率得到4-chloro-6-methoxy-7-(2-(pyrrolidin-1-yl)ethoxy)quinazoline
  参考文献：
  名称：

  Inhibition of tumor cell growth and angiogenesis by 7-Aminoalkoxy-4-aryloxy-quinazoline ureas, a novel series of multi-tyrosine kinase inhibitors

  摘要：

  Several regulatory and signaling molecules governing angiogenesis are targets of interest for the development of drugs in the cancer, including growth factors such as Vascular Endothelial Growth Factor (VEGF) and Platelet-Derived Growth Factor (PDGF). A series of 4-aryloxy-6,7-dimethoxyquinazolines, previously synthesized in our laboratory, has shown a nanomolar inhibition of kinase enzymatic activity of VEGFR, PDGFR and c-Kit. We have therefore studied the impact of the variation in the 7-position substitution of the quinazoline core. Substitution by aminoalkoxy chains led to new highly potent ATP-competitive inhibitors of VEGFR, PDGFR and c-Kit enzyme with IC50 values in the nanomolar range and this substitution has increased greatly antiproliferative activity on cancer cell lines (PC3, MCF7, HT29) and HUVEC (human umbilical vein endothelial cells). One of the most promising compounds (36) was assessed for its ability to limit the induction of web like network of capillary tubes by the human umbilical vascular endothelial cells (HUVEC) and for its ability to inhibit invasion. (C) 2014 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2014.04.007

文献信息

• Oxindole derivatives
  申请人：Zeneca Limited

  公开号：US06265411B1

  公开（公告）日：2001-07-24

  The invention relates to compounds of formula (I), wherein: R2 represents hydroxy, halogeno, C1-3alkyl, C1-3alkoxy, C1-3alkanoyloxy, trifluoromethyl, cyano, amino, nitro, C2-4alkanoyl, C1-4alkanoylamino, C1-4alkoxycarbonyl, C1-4alkylthio, C1-4alkylsulphinyl, C1-4alkylsulphonyl, carbamoyl, overscore (N)}—C1-4alkylcarbamoyl, overscore (N)},overscore (N)}-di(C1-4alkyl)carbamoyl, aminosulphonyl, overscore (N)}—C1-4alkylaminosulphonyl, overscore (N)},overscore (N)}-di(C1-4alkyl)aminosulphonyl, C1-4alkylsulphonylamino, or a group R4X1 wherein X1 represents a direct bond, C2-4alkanoyl, —CONR5R6—, —SO2NR7R8— or —SO2R9— (wherein R5 and R7, each independently represents hydrogen or C1-2alkyl and R6, R8 and R9 each independently represents C1-4alkyl and wherein R4 is linked to R6, R8 or R9) and R4 represents an optionally substituted group selected from phenyl and a 5 or 6-membered heterocyclic group; n is an integer from 0 to 4, R1 represents hydrogen, C1-4alkyl, C1-4alkoxymethyl, di(C1-4alkoxy)methyl or C1-4alkanoyl; m is an integer from 0 to 4; and R3 represents hydroxy, halogeno, nitro, trifluoromethyl, C1-3alkyl, cyano, amino or R10X2 (wherein X2 represents a direct bond, —CH2—, or a single or double heteroatom linker group including —S—, —SO— and —NR15— (wherein R15 represents hydrogen, C1-3alkyl or C1-3alkoxyC2-3alkyl), and R10 is an alkenyl or alkynyl chain optionally substituted by for example hydroxy, amino, nitro, alkyl, cycloalkyl, alkoxyalkyl, or an optionally substituted group selected from pyridone, phenyl and a heterocyclic ring, which alkyl, alkenyl or alkynyl chain may have a heteroatom linker group, or R10 is an optionally substituted group selected from pyridone, phenyl and a heterocyclic ring. The compounds of formula (I) and the pharmaceutically acceptable salts thereof inhibit the effects of VEGF and FGF, properties of value in the treatment of a number of disease states including cancer and rheumatoid arthritis.

  本发明涉及公式(I)的化合物，其中：R2代表羟基，卤素，C1-3烷基，C1-3烷氧基，C1-3烷氧酰基，三氟甲基，氰基，氨基，硝基，C2-4烷氧酰基，C1-4烷氧酰氨基，C1-4烷氧羰基，C1-4烷基亚硫酰基，C1-4烷基亚磺酰基，C1-4烷基亚磺酰基，碳酸酰基，N}-C1-4烷基碳酸酰基，N},N}-二(C1-4烷基)碳酸酰基，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，C1-4烷基亚磺酰氨基，或R4X1基团，其中X1代表直接键，C2-4烷氧酰基，-CONR5R6-，-SO2NR7R8-或-SO2R9-（其中R5和R7，每个独立地代表氢或C1-2烷基，R6，R8和R9每个独立地代表C1-4烷基，R4连接到R6，R8或R9），R4代表可选地取代的基团，选自苯基和5或6成员的杂环组；n是0到4的整数，R1代表氢，C1-4烷基，C1-4烷氧甲基，二(C1-4烷氧基)甲基或C1-4烷氧酰基；m是0到4的整数；R3代表羟基，卤素，硝基，三氟甲基，C1-3烷基，氰基，氨基或R10X2（其中X2代表直接键，-CH2-，或包括-S-，-SO-和-NR15-的单个或双杂原子连接基团（其中R15代表氢，C1-3烷基或C1-3烷氧基C2-3烷基），R10是可选地取代的烯基或炔基链，例如羟基，氨基，硝基，烷基，环烷基，烷氧基烷基，或从吡啶酮，苯基和杂环环中选择的可选地取代的基团，该烷基，烯基或炔基链可具有杂原子连接基团，或R10是可选地取代的基团，选自吡啶酮，苯基和杂环环。公式(I)的化合物及其药用盐抑制VEGF和FGF的活性，这些活性在包括癌症和类风湿性关节炎在内的多种疾病状态的治疗中具有重要价值。
• [EN] PHENOXYQUINAZOLINE COMPOUNDS AND THEIR USE IN TREATING CANCER<br/>[FR] COMPOSÉS DE PHÉNOXYQUINALZOLINE ET LEUR UTILISATION EN TRAITEMENT D'UN CANCER
  申请人：ASTRAZENECA AB

  公开号：WO2018197643A1

  公开（公告）日：2018-11-01

  The invention concerns compounds of Formula (I): or pharmaceutically acceptable salts thereof, wherein R1, R2, R3 and R4 have any of the meanings hereinbefore defined in the description; process for their preparation, pharmaceutical compositions containing them and their use in treating KIT mediated diseases.

  这项发明涉及Formula (I)的化合物或其药学上可接受的盐，其中R1、R2、R3和R4具有在描述中先前定义的任何含义；它们的制备方法，含有它们的药物组合物以及它们在治疗KIT介导疾病中的用途。
• QUINAZOLINE DERIVATIVES
  申请人：Jung Frederic Henri

  公开号：US20090233950A1

  公开（公告）日：2009-09-17

  The invention concerns quinazoline derivatives of Formula I or a pharmaceutically-acceptable salt thereof, wherein each of X 1 , p, R 1 , q, R 2 , R 3 , R 4 , R 5 , Ring A, r and R 6 has any of the meanings defined hereinbefore in the description; processes for their preparation, pharmaceutical compositions containing them and their use in the manufacture of a medicament for use in the treatment of cell proliferative disorders.

  该发明涉及公式I的喹唑啉衍生物或其药学上可接受的盐，其中X1、p、R1、q、R2、R3、R4、R5、环A、r和R6中的每一个都具有在说明中定义的任何含义；它们的制备方法，包含它们的制药组合物以及它们用于制造用于治疗细胞增殖性疾病的药物的用途。
• Phenoxyquinazoline compounds and their use in treating cancer
  申请人：AstraZeneca AB

  公开号：US11053223B2

  公开（公告）日：2021-07-06

  The invention concerns compounds of Formula (I): or pharmaceutically acceptable salts thereof, wherein R1, R2, R3 and R4 have any of the meanings hereinbefore defined in the description; process for their preparation, pharmaceutical compositions containing them and their use in treating KIT mediated diseases.

  本发明涉及式（I）化合物：或其药学上可接受的盐，其中 R1、R2、R3 和 R4 具有本文在描述中定义的任何含义；其制备工艺、含有它们的药物组合物及其在治疗 KIT 介导的疾病中的用途。
• WO2007/99317
  申请人：——

  公开号：——

  公开（公告）日：——