7-chloro-6-methyl-1H-benzo[d][1,3]oxazine-2,4-dione | 458533-67-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并恶嗪类
• 英文名称: 7-chloro-6-methyl-1H-benzo[d][1,3]oxazine-2,4-dione
• 英文别名: 7-chloro-6-methyl-1H-3,1-benzoxazine-2,4-dione
• CAS: 458533-67-0
• 化学式: C₉H₆ClNO₃
• 分子量: 211.605
• InChiKey: MIPHVIPWBBWEHT-UHFFFAOYSA-N

物化性质

• 熔点：
  257-260 °C
• 密度：
  1.463±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  14
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  55.4
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  7-chloro-6-methyl-1H-benzo[d][1,3]oxazine-2,4-dione 在 吡啶 、 2,6-二甲基吡啶 、 4-二甲氨基吡啶 、 sodium hydroxide 、 N-溴代丁二酰亚胺(NBS) 、 benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate 、 三乙胺 、 N,N-二异丙基乙胺 、 三氟乙酸 、 过氧化苯甲酰 作用下， 以 四氢呋喃 、 甲醇 、 四氯化碳 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 56.17h， 生成 CB 300919; 4-[[[7-氯-3,4-二氢-3-甲基-2-[(4-甲基-1-哌嗪基)甲基]-4-氧代-6-喹唑啉基]甲基]-2-丙炔-1-基氨基]-N-(3-吡啶基甲基)苯甲酰胺
  参考文献：
  名称：

  The Design and Synthesis of Water-Soluble Analogues of CB30865, a Quinazolin-4-one-Based Antitumor Agent

  摘要：

  4-[N-[7-Bromo-2-methyl-4-oxo-3,4-dihydroquinazolin-6-ylmethyl]-N-(prop-2-ynyl)amino]-N-(3-pyridylmethyl)benzamide (CB30865) is a quinazolin-4-one antitumor agent whose high growth-inhibitory activity (W1L2 IC50 = 2.8 +/- 0.50 nM) is believed to have a folate-independent locus of action. In addition, CB30865 represents a class of compounds with unique biochemical characteristics such as a delayed, non-phase specific, cell-cycle arrest. The low aqueous solubility of CB30865 prompted a search for more water-soluble analogues for in vivo evaluation of this class of compounds. It was thought that aqueous solubility could be increased by the introduction of amino functionalities at the 2-position of the quinazolin-4-one ring. A variety of compounds (5a-j, 31a-c, 32, and 33) were synthesized in a linear fashion starting from 3-chloro-4-methylaniline. Most of these compounds (e.g., 5a, 5b, 5g) were significantly more water-soluble than CB30865 (636 muM for 5a at pH 6 and 992 muM for 5g at pH 6). In addition, some of them were up to 6-fold more cytotoxic than CB30865 (e.g., for 5a, W1L2 IC50 = 0.49 +/- 0.24 nM) and retained its novel biochemical characteristics.

  DOI：

  10.1021/jm011081s
• 作为产物：
  描述：

  2-氨基-4-氯-5-甲基苯甲腈 在 氢氧化钾 、 双氧水 作用下， 以 四氢呋喃 为溶剂， 反应 8.0h， 生成 7-chloro-6-methyl-1H-benzo[d][1,3]oxazine-2,4-dione
  参考文献：
  名称：

  The Design and Synthesis of Water-Soluble Analogues of CB30865, a Quinazolin-4-one-Based Antitumor Agent

  摘要：

  4-[N-[7-Bromo-2-methyl-4-oxo-3,4-dihydroquinazolin-6-ylmethyl]-N-(prop-2-ynyl)amino]-N-(3-pyridylmethyl)benzamide (CB30865) is a quinazolin-4-one antitumor agent whose high growth-inhibitory activity (W1L2 IC50 = 2.8 +/- 0.50 nM) is believed to have a folate-independent locus of action. In addition, CB30865 represents a class of compounds with unique biochemical characteristics such as a delayed, non-phase specific, cell-cycle arrest. The low aqueous solubility of CB30865 prompted a search for more water-soluble analogues for in vivo evaluation of this class of compounds. It was thought that aqueous solubility could be increased by the introduction of amino functionalities at the 2-position of the quinazolin-4-one ring. A variety of compounds (5a-j, 31a-c, 32, and 33) were synthesized in a linear fashion starting from 3-chloro-4-methylaniline. Most of these compounds (e.g., 5a, 5b, 5g) were significantly more water-soluble than CB30865 (636 muM for 5a at pH 6 and 992 muM for 5g at pH 6). In addition, some of them were up to 6-fold more cytotoxic than CB30865 (e.g., for 5a, W1L2 IC50 = 0.49 +/- 0.24 nM) and retained its novel biochemical characteristics.

  DOI：

  10.1021/jm011081s

文献信息

• The Design and Synthesis of Water-Soluble Analogues of CB30865, a Quinazolin-4-one-Based Antitumor Agent
  作者：V. Bavetsias、L. A. Skelton、F. Yafai、F. Mitchell、S. C. Wilson、B. Allan、A. L. Jackman

  DOI：10.1021/jm011081s

  日期：2002.8.1

  4-[N-[7-Bromo-2-methyl-4-oxo-3,4-dihydroquinazolin-6-ylmethyl]-N-(prop-2-ynyl)amino]-N-(3-pyridylmethyl)benzamide (CB30865) is a quinazolin-4-one antitumor agent whose high growth-inhibitory activity (W1L2 IC50 = 2.8 +/- 0.50 nM) is believed to have a folate-independent locus of action. In addition, CB30865 represents a class of compounds with unique biochemical characteristics such as a delayed, non-phase specific, cell-cycle arrest. The low aqueous solubility of CB30865 prompted a search for more water-soluble analogues for in vivo evaluation of this class of compounds. It was thought that aqueous solubility could be increased by the introduction of amino functionalities at the 2-position of the quinazolin-4-one ring. A variety of compounds (5a-j, 31a-c, 32, and 33) were synthesized in a linear fashion starting from 3-chloro-4-methylaniline. Most of these compounds (e.g., 5a, 5b, 5g) were significantly more water-soluble than CB30865 (636 muM for 5a at pH 6 and 992 muM for 5g at pH 6). In addition, some of them were up to 6-fold more cytotoxic than CB30865 (e.g., for 5a, W1L2 IC50 = 0.49 +/- 0.24 nM) and retained its novel biochemical characteristics.