tert-butyl 4-[N-[7-chloro-3-methyl-2-(4-(2-hydroxyethyl)piperazin-1-ylmethyl)-4-oxo-3,4-dihydroquinazolin-6-ylmethyl]-N-(prop-2-ynyl)amino]benzoate | 289686-97-1

• 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: tert-butyl 4-[N-[7-chloro-3-methyl-2-(4-(2-hydroxyethyl)piperazin-1-ylmethyl)-4-oxo-3,4-dihydroquinazolin-6-ylmethyl]-N-(prop-2-ynyl)amino]benzoate
• 英文别名: Tert-butyl 4-[[7-chloro-2-[[4-(2-hydroxyethyl)piperazin-1-yl]methyl]-3-methyl-4-oxoquinazolin-6-yl]methyl-prop-2-ynylamino]benzoate
• CAS: 289686-97-1
• 化学式: C₃₁H₃₈ClN₅O₄
• 分子量: 580.127
• InChiKey: BZAQCGPEGRZVIB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  41
• 可旋转键数：
  11
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  88.9
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  tert-butyl 4-[N-[7-chloro-3-methyl-2-(4-(2-hydroxyethyl)piperazin-1-ylmethyl)-4-oxo-3,4-dihydroquinazolin-6-ylmethyl]-N-(prop-2-ynyl)amino]benzoate 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 生成 4-({7-Chloro-2-[4-(2-hydroxy-ethyl)-piperazin-1-ylmethyl]-3-methyl-4-oxo-3,4-dihydro-quinazolin-6-ylmethyl}-prop-2-ynyl-amino)-benzoic acid
  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：

  (7-氯-3,6-二甲基-4-氧代-3,4-二氢喹唑啉-2-基)乙酸甲酯 在 2,6-二甲基吡啶 、 sodium hydroxide 、 N-溴代丁二酰亚胺(NBS) 、 三乙胺 、 过氧化苯甲酰 作用下， 以 四氢呋喃 、 四氯化碳 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 11.25h， 生成 tert-butyl 4-[N-[7-chloro-3-methyl-2-(4-(2-hydroxyethyl)piperazin-1-ylmethyl)-4-oxo-3,4-dihydroquinazolin-6-ylmethyl]-N-(prop-2-ynyl)amino]benzoate
  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

• Anti-quinazoline compounds
  申请人：Cancer Research Technology Limited

  公开号：US06699861B1

  公开（公告）日：2004-03-02

  Dihydroquinazoline derivatives of the formula where R3 is —(CH2)p—A where p is from 1 to 4 and A is a 5- or 6-membered N-containing heterocyclic ring attached via the N atom or A is —NA′A″ wherein A′ and A″ are the same or different and are each a C1-C4 alkyl group or their pharmaceutically acceptable salts possessing anti-cancer activity.

  Dihydroquinazoline衍生物的化学式中，其中R3为—(CH2)p—A，其中p为1至4，A是通过N原子连接的含有5个或6个成员的N-含氮杂环环，或者A是—NA′A″，其中A′和A″相同或不同，分别为C1-C4烷基或其药学上可接受的盐，具有抗癌活性。