6,7-dimethoxy-2,2-dimethyl-4-methylsulfanyl-1,2-dihydro-quinazoline | 708268-04-6

• 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: 6,7-dimethoxy-2,2-dimethyl-4-methylsulfanyl-1,2-dihydro-quinazoline
• 英文别名: 6,7-dimethoxy-2,2-dimethyl-4-methylsulfanyl-1H-quinazoline
• CAS: 708268-04-6
• 化学式: C₁₃H₁₈N₂O₂S
• 分子量: 266.364
• InChiKey: IFDDBNZRFHWKHB-UHFFFAOYSA-N

物化性质

• 沸点：
  376.1±42.0 °C(Predicted)
• 密度：
  1.19±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  18
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  68.2
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  6,7-dimethoxy-2,2-dimethyl-4-methylsulfanyl-1,2-dihydro-quinazoline 在 盐酸 作用下， 生成 2-amino-N'-(3-bromophenyl)-4,5-dimethoxybenzenecarboximidamide
  参考文献：
  名称：

  Benzamides and benzamidines as specific inhibitors of epidermal growth factor receptor and v-Src protein tyrosine kinases

  摘要：

  The benzamides 1 and the benzamidines 2 as well as the cyclic benzamidines 3 were designed and synthesized as the mimics of 4-anilinoquinazolines for an inhibitor of EGFR tyrosine kinase. The specific inhibitions of EGFR tyrosine kinase were observed in the benzamides 1c and 1d, and the benzamidine 2a, whereas the specific inhibitions of v-Src kinase were observed in the benzamide 1j and the benzamidine 2d at a 10 mug/mL concentration of compounds. The cyclic benzamidines 3a and 3b showed potent kinase inhibition of EGFR at a 1.0 mug/mL concentration. According to the docking simulation using the X-ray structure of EGFR kinase domain in complex with erlotimb, the LigScore2 scoring function value of erlotimb was calculated as 5.61, whereas that of the benzamide 1c was 5.05. In a similar manner, the LigScore2 value of the cyclic benzamidine 3a was calculated as 5.10. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2004.04.030
• 作为产物：
  描述：

  2-氨基-4,5-二甲氧基苯甲酰胺 在 劳森试剂 、 对甲苯磺酸 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 6.0h， 生成 6,7-dimethoxy-2,2-dimethyl-4-methylsulfanyl-1,2-dihydro-quinazoline
  参考文献：
  名称：

  Benzamides and benzamidines as specific inhibitors of epidermal growth factor receptor and v-Src protein tyrosine kinases

  摘要：

  The benzamides 1 and the benzamidines 2 as well as the cyclic benzamidines 3 were designed and synthesized as the mimics of 4-anilinoquinazolines for an inhibitor of EGFR tyrosine kinase. The specific inhibitions of EGFR tyrosine kinase were observed in the benzamides 1c and 1d, and the benzamidine 2a, whereas the specific inhibitions of v-Src kinase were observed in the benzamide 1j and the benzamidine 2d at a 10 mug/mL concentration of compounds. The cyclic benzamidines 3a and 3b showed potent kinase inhibition of EGFR at a 1.0 mug/mL concentration. According to the docking simulation using the X-ray structure of EGFR kinase domain in complex with erlotimb, the LigScore2 scoring function value of erlotimb was calculated as 5.61, whereas that of the benzamide 1c was 5.05. In a similar manner, the LigScore2 value of the cyclic benzamidine 3a was calculated as 5.10. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2004.04.030

文献信息

• Synthesis and biological evaluation of benzamides and benzamidines: structural requirement of a pyrimidine ring for inhibition of EGFR tyrosine kinase
  作者：Toru Asano、Tomohiro Yoshikawa、Hiroyuki Nakamura、Yoshimasa Uehara、Yoshinori Yamamoto

  DOI：10.1016/j.bmcl.2004.02.001

  日期：2004.5

  The benzamides 1 and the benzamidines 2-3 were synthesized as the mimics of 4-anilinoquinazolines, which possess inhibition of epidermal growth factor receptor (EGER) tyrosine kinase, and tested for cytotoxicity toward A431 and inhibitory activity toward autophosphorylation by the enzyme assay. High cell growth inhibition was observed in a series of the cyclic benzamides 3: the IC50 values are 0.09-0.32 mM. The benzamidines 3a and 3b exhibited high inhibition of EGER tyrosine kinase at a 1.0 muM concentration, although the benzamides 1 and the benzamidines 2 did not show significant kinase inhibition at a 10 muM concentration. (C) 2004 Elsevier Ltd. All rights reserved.