6-chloro-3-(1H-indazol-3-yl)-2-methylquinazolin-4-one | 247174-92-1

• 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: 6-chloro-3-(1H-indazol-3-yl)-2-methylquinazolin-4-one
• CAS: 247174-92-1
• 化学式: C₁₆H₁₁ClN₄O
• 分子量: 310.743
• InChiKey: OEINIBNEALCFPH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  22
• 可旋转键数：
  1
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  61.4
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  苯甲醛 、 6-chloro-3-(1H-indazol-3-yl)-2-methylquinazolin-4-one 在 溶剂黄146 作用下， 反应 12.0h， 以13%的产率得到6-Chloro-3-(1H-indazol-3-yl)-2-((E)-styryl)-3H-quinazolin-4-one
  参考文献：
  名称：

  Synthesis, cytotoxicity, and inhibitory effects on tubulin polymerization of a new 3-heterocyclo substituted 2-styrylquinazolinones

  摘要：

  In order to study the influence of 3-substitution on the cytotoxic activity of 2-styrylquinazolinones, new 6-chloro-2-styryl-3-(heteroaryl)-4(3H)-quinazolinones were synthesized by refluxing equimolar amounts of 6-chloro-2-methyl-3-(heteroaryl)-4(3H)-quinazolinones and benzaldehyde in glacial acetic acid. At 1 mug ml(-1) concentration, almost all 2-styrylquinazolinones showed some cytotoxic activity against the L1210 and K562 leukemia cell lines. However, only 6-chloro-2-styryl-3-(pyrimidin-2yl)-4(3H)-quinazolinone inhibited the growth of these cells by over 50%. This last compound was also the only member of the series that inhibited tubulin polymerization, with air IC50 value of 5.8 versus 3.2 muM for colchicine. It was also examined for effects on the growth of human MCF7 breast carcinoma cells and Burkitt lymphoma CA46 cells, which had IC50 values of 0.34 and 1.0 muM, respectively. At 10 muM 6-chloro-2-styryl-3-(pyrimidin-2yl)-4(3H)-quinazolinone induced G2/M arrest (66%) in Burkitt cells, with a mitotic index of 20%. At 3.4 muM, it caused disruption of the cellular microtubule system of the MCF7 cells. Both these cellular effects are consistent with its mechanism of action resulting from its inhibitory effect on tubulin assembly. (C) 2004 Elsevier SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2003.12.009
• 作为产物：
  描述：

  3-氨基吲唑 在 吡啶 、 盐酸 、 tin(ll) chloride 作用下， 反应 5.0h， 生成 6-chloro-3-(1H-indazol-3-yl)-2-methylquinazolin-4-one
  参考文献：
  名称：

  Synthesis and Antiproliferative Activity of Novel 3-(Indazol-3-yl)-quinazolin-4(3H)-one and 3-(Indazol-3-yl)-benzotriazin-4(3H)-one Derivatives

  摘要：

  Several new 3-(indazol-3-yl)-quinazolin-4(3H)-one and 3-(indazol-3-yl)-benzotriazin-4(3H)-one derivatives 5 and 6 were synthesized and tested for their in vitro, antiproliferative activity against Raji, K562, and K562-R cell lines. The pharmacological screening showed that some 2, 6, or 7-substituted quinazolinones 5 posses a significant antiproliferative activity, with a percentage growth inhibition ranging from 44.8% to 100% at 50 mu M, which was higher than that showed by the unsubstituted derivative 5a previously synthesized. For the most active compounds 5d, 5f, and 5g the IC50 were recorded.

  DOI：

  10.1002/(sici)1521-4184(19999)332:9<317::aid-ardp317>3.0.co;2-r

文献信息

• Synthesis and Antiproliferative Activity of Novel 3-(Indazol-3-yl)-quinazolin-4(3H)-one and 3-(Indazol-3-yl)-benzotriazin-4(3H)-one Derivatives
  作者：Demetrio Raffa、Giuseppe Daidone、Benedetta Maggio、Domenico Schillaci、Fabiana Plescia

  DOI：10.1002/(sici)1521-4184(19999)332:9<317::aid-ardp317>3.0.co;2-r

  日期：1999.9

  Several new 3-(indazol-3-yl)-quinazolin-4(3H)-one and 3-(indazol-3-yl)-benzotriazin-4(3H)-one derivatives 5 and 6 were synthesized and tested for their in vitro, antiproliferative activity against Raji, K562, and K562-R cell lines. The pharmacological screening showed that some 2, 6, or 7-substituted quinazolinones 5 posses a significant antiproliferative activity, with a percentage growth inhibition ranging from 44.8% to 100% at 50 mu M, which was higher than that showed by the unsubstituted derivative 5a previously synthesized. For the most active compounds 5d, 5f, and 5g the IC50 were recorded.
• Synthesis, cytotoxicity, and inhibitory effects on tubulin polymerization of a new 3-heterocyclo substituted 2-styrylquinazolinones
  作者：Demetrio Raffa、Michael C. Edler、Giuseppe Daidone、Benedetta Maggio、Mourad Merickech、Salvatore Plescia、Domenico Schillaci、Ruoli Bai、Ernest Hamel

  DOI：10.1016/j.ejmech.2003.12.009

  日期：2004.4

  In order to study the influence of 3-substitution on the cytotoxic activity of 2-styrylquinazolinones, new 6-chloro-2-styryl-3-(heteroaryl)-4(3H)-quinazolinones were synthesized by refluxing equimolar amounts of 6-chloro-2-methyl-3-(heteroaryl)-4(3H)-quinazolinones and benzaldehyde in glacial acetic acid. At 1 mug ml(-1) concentration, almost all 2-styrylquinazolinones showed some cytotoxic activity against the L1210 and K562 leukemia cell lines. However, only 6-chloro-2-styryl-3-(pyrimidin-2yl)-4(3H)-quinazolinone inhibited the growth of these cells by over 50%. This last compound was also the only member of the series that inhibited tubulin polymerization, with air IC50 value of 5.8 versus 3.2 muM for colchicine. It was also examined for effects on the growth of human MCF7 breast carcinoma cells and Burkitt lymphoma CA46 cells, which had IC50 values of 0.34 and 1.0 muM, respectively. At 10 muM 6-chloro-2-styryl-3-(pyrimidin-2yl)-4(3H)-quinazolinone induced G2/M arrest (66%) in Burkitt cells, with a mitotic index of 20%. At 3.4 muM, it caused disruption of the cellular microtubule system of the MCF7 cells. Both these cellular effects are consistent with its mechanism of action resulting from its inhibitory effect on tubulin assembly. (C) 2004 Elsevier SAS. All rights reserved.