5-(benzyloxy)-4-chloro-6-methoxyquinazoline | 120075-53-8

• 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: 5-(benzyloxy)-4-chloro-6-methoxyquinazoline
• 英文别名: 4-Chloro-6-methoxy-5-phenylmethoxyquinazoline
• CAS: 120075-53-8
• 化学式: C₁₆H₁₃ClN₂O₂
• 分子量: 300.744
• InChiKey: KTEWUVRMFUNSCQ-UHFFFAOYSA-N

物化性质

• 沸点：
  452.1±40.0 °C(Predicted)
• 密度：
  1.303±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  21
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  44.2
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  5-(benzyloxy)-4-chloro-6-methoxyquinazoline 在 palladium on activated charcoal potassium dihydrogenphosphate 、 potassium nitrososulfonate 、 氢气 、 三乙胺 作用下， 以 1,4-二氧六环 、 甲醇 、 乙醇 、 水 为溶剂， 25.0 ℃ 、101.33 kPa 条件下， 反应 32.5h， 生成 6,7-二(氮丙啶-1-基)-4-(3-二甲基氨基丙基氨基)喹唑啉-5,8-二酮
  参考文献：
  名称：

  Heterocyclic quinones. XVII. A new in vivo active antineoplastic drug: 6,7-bis(1-aziridinyl)-4-[[3-(N,N-dimethylamino)propyl]amino]-5,8-quinazolinedione

  摘要：

  A series of heterocyclic quinones 6-substituted and 6,7-disubstituted 4-(alkylamino)-5,8-quinazolinediones, have been synthesized in order to evaluate their in vitro cytotoxicity on L1210 leukemia cells. Among 14 derivatives that have been prepared and studied for the structure-activity relationship, the most potent cytotoxic compound on L1210 leukemia cells was the 6,7-bis(1-aziridinyl)-4-[[3-(N,N-dimethylamino)propyl]amino]-5,8-quinazolinedione (24). This compound has been tested with the use of a cell-image processor on MCF-7 human mammary and HBL human melanoma cell lines. The results show that compound 24 influences cell proliferation and blocks both cells lines in the S phase. In vivo antineoplastic activity of compound 24 has been demonstrated on a broad spectrum of murine experimental models, but it was found highly toxic and produced long-delayed deaths.

  DOI：

  10.1021/jm00105a007
• 作为产物：
  描述：

  2-(benzyloxy)-3-methoxy-6-nitrobenzaldehyde 在 哌啶 、 ammonium hydroxide 、 potassium permanganate 、 iron(II) sulfate 、 三乙胺 、 三氯氧磷 作用下， 以 乙醇 、 水 、 丙酮 、 苯 为溶剂， 反应 47.5h， 生成 5-(benzyloxy)-4-chloro-6-methoxyquinazoline
  参考文献：
  名称：

  杂环醌。十三。5,8-喹唑啉二酮系列中的二聚化：双（4-氨基-5,8-喹唑啉二酮）的合成和抗肿瘤作用。

  摘要：

  为了获得比以前描述的 5，8-喹唑啉二酮更有效的抗肿瘤新药，我们研究了一系列 5，8-喹唑啉二酮的二聚体，这些二聚体在 4 位通过简单或取代的 χ，ω-二氨基多亚甲基链连接。研究讨论了这些化合物的结构-活性关系，包括链的长度、是否存在其他官能团、这些官能团的性质、链的位置以及 6 位和（或）7 位取代基的性质。当双（5，8-喹唑啉二酮）的 6 位被甲氧基取代时，二聚物对 L 1210 白血病细胞的细胞毒性有不同的影响。双[4-氨基-双-6, 7 (1-氮丙啶基)-5, 8-喹唑啉二酮]表现出很高的细胞毒性活性（IC50 0.0037 至 0.018μm），我们进一步在体内筛选了它们对小鼠 P388 白血病的活性。分子的二聚化提高了抗肿瘤活性。最有效的化合物在链上具有额外的三级氨基功能。

  DOI：

  10.1248/cpb.36.3933

文献信息

• RENAULT, JEAN ARMAND PAUL;GIORGI, SYLVIANE MADELEINE JEANNE;GEBEL, PATRIC+
  作者：RENAULT, JEAN ARMAND PAUL、GIORGI, SYLVIANE MADELEINE JEANNE、GEBEL, PATRIC+

  DOI：——

  日期：——
• GIORGI-RENAULT, SYLVIANE;RENAULT, JEAN;CEBEL-SERVOLLES, PATRICIA;BARON, M+, J. MED. CHEM., 34,(1991) N, C. 38-46
  作者：GIORGI-RENAULT, SYLVIANE、RENAULT, JEAN、CEBEL-SERVOLLES, PATRICIA、BARON, M+

  DOI：——

  日期：——
• GIORGI-RENAULT, SYLVIANE;RENAULT, JEAN;BARON, MICHEL;GEBEL-SERVOLLES, PAT+, CHEM. AND PHARM. BULL., 36,(1988) N 10, C. 3933-3947
  作者：GIORGI-RENAULT, SYLVIANE、RENAULT, JEAN、BARON, MICHEL、GEBEL-SERVOLLES, PAT+

  DOI：——

  日期：——
• Heterocyclic quinones. XVII. A new in vivo active antineoplastic drug: 6,7-bis(1-aziridinyl)-4-[[3-(N,N-dimethylamino)propyl]amino]-5,8-quinazolinedione
  作者：Sylviane Giorgi-Renault、Jean Renault、Patricia Gebel-Servolles、Michel Baron、Claude Paoletti、Suzanne Cros、Marie Christine Bissery、Francois Lavelle、Ghanem Atassi

  DOI：10.1021/jm00105a007

  日期：1991.1

  A series of heterocyclic quinones 6-substituted and 6,7-disubstituted 4-(alkylamino)-5,8-quinazolinediones, have been synthesized in order to evaluate their in vitro cytotoxicity on L1210 leukemia cells. Among 14 derivatives that have been prepared and studied for the structure-activity relationship, the most potent cytotoxic compound on L1210 leukemia cells was the 6,7-bis(1-aziridinyl)-4-[[3-(N,N-dimethylamino)propyl]amino]-5,8-quinazolinedione (24). This compound has been tested with the use of a cell-image processor on MCF-7 human mammary and HBL human melanoma cell lines. The results show that compound 24 influences cell proliferation and blocks both cells lines in the S phase. In vivo antineoplastic activity of compound 24 has been demonstrated on a broad spectrum of murine experimental models, but it was found highly toxic and produced long-delayed deaths.
• Heterocyclic quinones. XIII. Dimerization in the series of 5,8-quinazolinediones: Synthesis and antitumor effects of bis(4-amino-5,8-quinazolinediones).
  作者：SYLVIANE GIORGI-RENAULT、JEAN RENAULT、MICHEL BARON、PATRICIA GEBEL-SERVOLLES、Jozo DELIC、SUZANNE CROS、CLAUDE PAOLETTI

  DOI：10.1248/cpb.36.3933

  日期：——

  With the aim of obtaining new antitumor drugs more active than previously described 5, 8-quinazolinediones, a series of dimers of 5, 8-quinazolinediones linked in the 4-position by a simple or a substituted χ, ω-diaminopolymethylenic chain was studied. The structure-activity relationships of these compounds are discussed as functions of the length of the chain, presence or absence of other functional groups, nature of these functional groups, position of the chain and nature of the substituents in the 6 and (or) 7-positions. When bis (5, 8-quinazolinediones) were substituted in the 6-position with a methoxyl group, the dimerization showed a variable effect on cytotoxicity toward L 1210 leukemia cells. Bis [4-amino-bis-6, 7 (1-aziridinyl)-5, 8-quinazolinediones] which exhibited high cytotoxic activity (IC50 0.0037 to 0.018μm) were further screened in vivo for activity against murine P388 leukemia. Antitumor activity was increased by the dimerization of the molecule. The most potent compound bears an additional tertiary amino function on the chain.

  为了获得比以前描述的 5，8-喹唑啉二酮更有效的抗肿瘤新药，我们研究了一系列 5，8-喹唑啉二酮的二聚体，这些二聚体在 4 位通过简单或取代的 χ，ω-二氨基多亚甲基链连接。研究讨论了这些化合物的结构-活性关系，包括链的长度、是否存在其他官能团、这些官能团的性质、链的位置以及 6 位和（或）7 位取代基的性质。当双（5，8-喹唑啉二酮）的 6 位被甲氧基取代时，二聚物对 L 1210 白血病细胞的细胞毒性有不同的影响。双[4-氨基-双-6, 7 (1-氮丙啶基)-5, 8-喹唑啉二酮]表现出很高的细胞毒性活性（IC50 0.0037 至 0.018μm），我们进一步在体内筛选了它们对小鼠 P388 白血病的活性。分子的二聚化提高了抗肿瘤活性。最有效的化合物在链上具有额外的三级氨基功能。