6-methoxy-7-[3-(pyrrolidin-1-yl)propoxy]-3,4-dihydroquinazolin-4-one | 199327-75-8

• 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: 6-methoxy-7-[3-(pyrrolidin-1-yl)propoxy]-3,4-dihydroquinazolin-4-one
• 英文别名: 6-Methoxy-7-(3-pyrrolidin-1-ylpropoxy)-3,4-dihydroquinazolin-4-one；6-methoxy-7-(3-pyrrolidin-1-ylpropoxy)-3H-quinazolin-4-one
• CAS: 199327-75-8
• 化学式: C₁₆H₂₁N₃O₃
• 分子量: 303.361
• InChiKey: AOKBXCYRXJZEGX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  22
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  63.2
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  6-methoxy-7-[3-(pyrrolidin-1-yl)propoxy]-3,4-dihydroquinazolin-4-one 在 氯化亚砜 、 sodium hydride 、 N,N-二甲基甲酰胺 作用下， 以 四氢呋喃 为溶剂， 反应 16.0h， 生成 N-mesityl-2-(6-methoxy-7-(3-(pyrrolidin-1-yl)propoxy)quinazolin-4-ylamino)benzo[d]thiazole-6-carboxamide
  参考文献：
  名称：

  Design and synthesis of novel 4-benzothiazole amino quinazolines Dasatinib derivatives as potential anti-tumor agents

  摘要：

  Three series of novel 4-benzothiazole amino quinazolines Dasatinib derivatives have been designed and synthesized. The entire target compounds were investigated for their in vitro cytotoxic activity by the MTT-based assay against 6 human cancer cell lines. Compared with the parental Dasatinib, most of the new compounds, especially 2, 4, 6-trimethylaniline series (3), demonstrated significant inhibitory activities against six cell lines. Furthermore, the target compounds were screened for Src and Abl kinase inhibitory activity. Among them, 1a, 1f and 3a-3f are more potential dual Src/Abl kinase inhibitors. Thus they may be promising lead compounds to be developed as an alternative for current Dasatinib therapy or for Imatinib-resistant patients, potentially via simultaneously blocking multiple RTK signaling pathways. (c) 2013 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2013.03.013
• 作为产物：
  描述：

  6-甲氧基-7-羟基喹唑啉-4-酮 在 铁粉 、 potassium carbonate 、 溶剂黄146 、 三乙胺 、 sodium hydroxide 作用下， 以 四氢呋喃 、 N,N-dimethyl-d₆-formamide 、 苯 为溶剂， 反应 22.0h， 生成 6-methoxy-7-[3-(pyrrolidin-1-yl)propoxy]-3,4-dihydroquinazolin-4-one
  参考文献：
  名称：

  一种西地尼布中间体的制备方法

  摘要：

  本发明公开了一种西地尼布中间体的制备方法，所述西地尼布中间体化学名为4‑氯‑6‑甲氧基‑7‑[3‑(吡咯烷‑1‑基)丙氧基]喹唑啉，其结构式为：；本发明采用了以6‑甲氧基‑7‑羟基‑3,4‑二氢喹唑啉‑4‑酮为原料经过缩合反应、还原反应、环合反应及氯化反应进行制备，无需进行多次基团保护与脱保护，反应条件温和、成本低、合成步骤短、副产物少，总收率较高，更加适合工业化生产。

  公开号：

  CN108129401A

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。
• Quinazoline derivatives with anti-tumour activity
  申请人：AstraZeneca AB

  公开号：US20040048881A1

  公开（公告）日：2004-03-11

  The invention concerns quinazoline derivatives of Formula I 1 wherein each of m, R 1 , n, R 2 and R 3 have any of the meanings defined in the description; processes for their preparation, pharmaceutical compositions containing them and their use in the manufacture of a medicament for use as an anti-invasive agent in the containment and/or treatment of solid tumour disease.

  这项发明涉及式I的喹唑啉衍生物，其中m、R1、n、R2和R3中的每一个具有描述中定义的任意含义；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作抗侵袭剂的药物的过程中在固体肿瘤疾病的控制和/或治疗中的使用。
• Quinazoline derivatives
  申请人：——

  公开号：US20040044015A1

  公开（公告）日：2004-03-04

  The invention concerns quinazoline derivatives of Formula (I) wherein each of m, R 1 , n, R 2 and R 3 have any of the meanings defined in the description; process for the preparation, pharmaceutical compositions them and their use in the manufacture of a medicament for use as an anti-invasive agent in the containment and/or treatment of solid tumour disease.

  这项发明涉及式（I）的喹唑啉衍生物，其中m、R1、n、R2和R3中的每一个具有描述中定义的任意含义；制备过程，药物组合物及其在制备用作抗侵袭剂的药物中的使用，用于包含和/或治疗固体肿瘤疾病。
• 一种西地尼布中间体的制备方法
  申请人：董丹丹

  公开号：CN108129401A

  公开（公告）日：2018-06-08

  本发明公开了一种西地尼布中间体的制备方法，所述西地尼布中间体化学名为4‑氯‑6‑甲氧基‑7‑[3‑(吡咯烷‑1‑基)丙氧基]喹唑啉，其结构式为：；本发明采用了以6‑甲氧基‑7‑羟基‑3,4‑二氢喹唑啉‑4‑酮为原料经过缩合反应、还原反应、环合反应及氯化反应进行制备，无需进行多次基团保护与脱保护，反应条件温和、成本低、合成步骤短、副产物少，总收率较高，更加适合工业化生产。
• 一种抗癌肿药物西地尼布的制备方法
  申请人：董丹丹

  公开号：CN108084165A

  公开（公告）日：2018-05-29

  本发明公开了一种抗癌肿药物西地尼布的制备方法，所述抗癌肿药物西地尼布化学名称为4‑(4‑氟‑2‑甲基吲哚‑5‑基氧基)‑6‑甲氧基‑7‑[3‑(吡咯烷‑1‑基)丙氧基]喹唑啉，其化学式为C25H27FN4O3，其结构式为：；本发明通过醚化反应与还原反应生成4‑[（2‑氟‑4‑氨基）苯基]氧基‑6‑甲氧基‑7‑[3‑(吡咯烷‑1‑基)丙氧基]喹唑啉,最终通过氧化环合反应生成西地尼布，避免了通过现有的氯化反应合成而导致使用对环境有害的三氯化磷、五氯化磷、二氯亚砜、光气或三氯氧磷等氯化剂，保护了环境，工艺过程简洁，快捷方便，原料易得，经济环保，产品收率与产品纯度高，质量可控，适合工业化生产。