2-(3-methoxyphenyl)-6-morpholino-3H-quinazolin-4-one

• 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: 2-(3-methoxyphenyl)-6-morpholino-3H-quinazolin-4-one
• 英文别名: 2-(3-methoxyphenyl)-6-morpholin-4-yl-3H-quinazolin-4-one
• 化学式: C₁₉H₁₉N₃O₃
• 分子量: 337.378
• InChiKey: KHMGRMISMYGXLU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  25
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  63.2
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  5-氯-2-硝基苯甲酸 在 10percent Pd/C 氯化亚砜 、 氨 、 氢气 、 sodium hydrogensulfite 作用下， 以 甲醇 、 N,N-二甲基乙酰胺 、 N,N-二甲基甲酰胺 、 苯 为溶剂， 反应 15.0h， 生成 2-(3-methoxyphenyl)-6-morpholino-3H-quinazolin-4-one
  参考文献：
  名称：

  6-Alkylamino- and 2,3-Dihydro-3‘-methoxy-2-phenyl-4-quinazolinones and Related Compounds:  Their Synthesis, Cytotoxicity, and Inhibition of Tubulin Polymerization

  摘要：

  As part of our continuing search for potential anticancer candidates among 2-phenyl-4-quinolones and 2-phenyl-4-quinazolinones, two series of 6,7,2',3',4',5'-substituted 2-phenyl-4-quinazolinones and 6,2',3',4',5'-substituted 2,3-dihydro-2-phenyl-4-quinazolinones were synthesized and evaluated for cytotoxicity and as inhibitors of tubulin polymerization. In general, a good correlation was found between the two activities. Five of the 6-substituted heterocyclic 2-phenyl-4-quinozolinones (37-51) showed significant cytotoxicity against a panel of human tumor cell lines with EC50 values in the low micromolar to nanomolar concentration ranges. Compound 38 was the most potent of these compounds, as well as the most potent inhibitor of tubulin polymerization in this series. The activity of 38 was in the same range as those of the antimitotic natural products, colchicine, podophyllotoxin, and combretastatin A-4. Substituted 2-phenyl-4-quinazolinones and 2,3-dihydro-2-phenyl-4-quinazolinones also displayed highly selective cytotoxicity against the ovarian cancer 1A9 and P-gp resistant KB-VIN cell lines.

  DOI：

  10.1021/jm000151c

文献信息

• 2-phenyl-4-quinazolinone compounds, 2-phenyl-4-alkoxy-quinazoline compounds and their pharmaceutical compositions
  申请人：National Science Council

  公开号：US06479499B1

  公开（公告）日：2002-11-12

  Two series of 6,7,2′,3′,4′,5′-substituted 2-phenyl-4-quinazolinones and 6,2′,3′,4′,5′-substituted 2,3-dihydro-2-phenyl-4-quinazolinones are synthesized and evaluated for cytotoxicity against a panel of human tumor cell lines, such as epidermoid carcinoma of the nasopharynx (KB), lung carcinoma (A-549), ileocecal carcinoma (HCT-8), breast cancer (MCF-7), melanoma (SKMEL-2), ovarian cancer (1A9), glioblastoma (U-87-MG), bone (HOS), P-gp-expressing epidermoid carcinoma of the nasopharynx (KB-VIN), and prostate cancer (PC3) cell lines, and some of the compounds are found potent. The present invention also synthesizes 2-phenyl-4-alkoxy-quinazoline compounds, wherein some of the compounds exhibit antiplatelet activity.

  合成了两种系列的化合物，分别是6,7,2′,3′,4′,5′-取代的2-苯基-4-喹唑啉酮和6,2′,3′,4′,5′-取代的2,3-二氢-2-苯基-4-喹唑啉酮，并评价了它们对人肿瘤细胞系如鼻咽癌上皮细胞癌（KB）、肺癌（A-549）、回肠癌（HCT-8）、乳腺癌（MCF-7）、黑色素瘤（SKMEL-2）、卵巢癌（1A9）、胶质母细胞瘤（U-87-MG）、骨肉瘤（HOS）、表达P-gp的鼻咽癌上皮细胞癌（KB-VIN）和前列腺癌（PC3）细胞系的细胞毒性，发现其中一些化合物具有显著的活性。本发明还合成了2-苯基-4-烷氧基喹唑啉化合物，其中一些化合物显示出抗血小板活性。
• US6479499B1
  申请人：——

  公开号：US6479499B1

  公开（公告）日：2002-11-12
• 6-Alkylamino- and 2,3-Dihydro-3‘-methoxy-2-phenyl-4-quinazolinones and Related Compounds:  Their Synthesis, Cytotoxicity, and Inhibition of Tubulin Polymerization
  作者：Mann-Jen Hour、Li-Jiau Huang、Sheng-Chu Kuo、Yi Xia、Kenneth Bastow、Yuka Nakanishi、Ernest Hamel、Kuo-Hsiung Lee

  DOI：10.1021/jm000151c

  日期：2000.11.1

  As part of our continuing search for potential anticancer candidates among 2-phenyl-4-quinolones and 2-phenyl-4-quinazolinones, two series of 6,7,2',3',4',5'-substituted 2-phenyl-4-quinazolinones and 6,2',3',4',5'-substituted 2,3-dihydro-2-phenyl-4-quinazolinones were synthesized and evaluated for cytotoxicity and as inhibitors of tubulin polymerization. In general, a good correlation was found between the two activities. Five of the 6-substituted heterocyclic 2-phenyl-4-quinozolinones (37-51) showed significant cytotoxicity against a panel of human tumor cell lines with EC50 values in the low micromolar to nanomolar concentration ranges. Compound 38 was the most potent of these compounds, as well as the most potent inhibitor of tubulin polymerization in this series. The activity of 38 was in the same range as those of the antimitotic natural products, colchicine, podophyllotoxin, and combretastatin A-4. Substituted 2-phenyl-4-quinazolinones and 2,3-dihydro-2-phenyl-4-quinazolinones also displayed highly selective cytotoxicity against the ovarian cancer 1A9 and P-gp resistant KB-VIN cell lines.