N⁴-(3-Bromo-phenyl)-N⁷,N⁷-dimethyl-6-nitro-quinazoline-4,7-diamine | 171745-09-8

• 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: N⁴-(3-Bromo-phenyl)-N⁷,N⁷-dimethyl-6-nitro-quinazoline-4,7-diamine
• 英文别名: 4-N-(3-bromophenyl)-7-N,7-N-dimethyl-6-nitroquinazoline-4,7-diamine
• CAS: 171745-09-8
• 化学式: C₁₆H₁₄BrN₅O₂
• 分子量: 388.223
• InChiKey: GOUUCLJKCPCYMJ-UHFFFAOYSA-N

物化性质

• 沸点：
  541.4±50.0 °C(Predicted)
• 密度：
  1.603±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  24
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  86.9
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  N⁴-(3-Bromo-phenyl)-N⁷,N⁷-dimethyl-6-nitro-quinazoline-4,7-diamine 在 铁粉 作用下， 以 乙醇 、 水 为溶剂， 生成 N⁴-(3-Bromo-phenyl)-N⁷,N⁷-dimethyl-quinazoline-4,6,7-triamine
  参考文献：
  名称：

  Tyrosine Kinase Inhibitors. 8. An Unusually Steep Structure−Activity Relationship for Analogues of 4-(3-Bromoanilino)-6,7-dimethoxyquinazoline (PD 153035), a Potent Inhibitor of the Epidermal Growth Factor Receptor

  摘要：

  4-(3-Bromoanilino)-6,7-dimethoxyquinazoline (32, PD 153035) is a very potent inhibitor (IC50 0.025 nM) of the tyrosine kinase activity of the epidermal growth factor receptor (EGFR), binding competitively at the ATP site. Structure-activity relationships for close analogues of 32 are very steep. Some derivatives have IC(50)s UP to 80-fold better than predicted from simple additive binding energy arguments, yet analogues possessing combinations of similar phenyl and quinazoline substituents do not show this ''supra-additive'' effect. Because some substituents which are mildly deactivating by themselves can be strongly activating when used in the correct combinations, it is proposed that certain substituted analogues possess the ability to induce a change in the conformation of the receptor when they bind. There is some bulk tolerance for substitution in the 6- and 7-positions of the quinazoline, so that 32 is not the optimal inhibitor for the induced conformation. The diethoxy derivative 56 [4-(3-bromoanilino)-6,7-diethoxyquinazoline] shows an IC50 Of 0.006 nM, making it the most potent inhibitor of the tyrosine kinase activity of the EGFR yet reported.

  DOI：

  10.1021/jm9503613
• 作为产物：
  描述：

  4,7-二氯-6-硝基喹唑啉 在 盐酸 作用下， 以 乙醇 、 水 、 异丙醇 为溶剂， 反应 1.5h， 生成 N⁴-(3-Bromo-phenyl)-N⁷,N⁷-dimethyl-6-nitro-quinazoline-4,7-diamine
  参考文献：
  名称：

  Tyrosine Kinase Inhibitors. 8. An Unusually Steep Structure−Activity Relationship for Analogues of 4-(3-Bromoanilino)-6,7-dimethoxyquinazoline (PD 153035), a Potent Inhibitor of the Epidermal Growth Factor Receptor

  摘要：

  4-(3-Bromoanilino)-6,7-dimethoxyquinazoline (32, PD 153035) is a very potent inhibitor (IC50 0.025 nM) of the tyrosine kinase activity of the epidermal growth factor receptor (EGFR), binding competitively at the ATP site. Structure-activity relationships for close analogues of 32 are very steep. Some derivatives have IC(50)s UP to 80-fold better than predicted from simple additive binding energy arguments, yet analogues possessing combinations of similar phenyl and quinazoline substituents do not show this ''supra-additive'' effect. Because some substituents which are mildly deactivating by themselves can be strongly activating when used in the correct combinations, it is proposed that certain substituted analogues possess the ability to induce a change in the conformation of the receptor when they bind. There is some bulk tolerance for substitution in the 6- and 7-positions of the quinazoline, so that 32 is not the optimal inhibitor for the induced conformation. The diethoxy derivative 56 [4-(3-bromoanilino)-6,7-diethoxyquinazoline] shows an IC50 Of 0.006 nM, making it the most potent inhibitor of the tyrosine kinase activity of the EGFR yet reported.

  DOI：

  10.1021/jm9503613

文献信息

• Tyrosine Kinase Inhibitors. 8. An Unusually Steep Structure−Activity Relationship for Analogues of 4-(3-Bromoanilino)-6,7-dimethoxyquinazoline (PD 153035), a Potent Inhibitor of the Epidermal Growth Factor Receptor
  作者：Alexander J. Bridges、Hairong Zhou、Donna R. Cody、Gordon W. Rewcastle、Amy McMichael、H. D. Hollis Showalter、David W. Fry、Alan J. Kraker、William A. Denny

  DOI：10.1021/jm9503613

  日期：1996.1.1

  4-(3-Bromoanilino)-6,7-dimethoxyquinazoline (32, PD 153035) is a very potent inhibitor (IC50 0.025 nM) of the tyrosine kinase activity of the epidermal growth factor receptor (EGFR), binding competitively at the ATP site. Structure-activity relationships for close analogues of 32 are very steep. Some derivatives have IC(50)s UP to 80-fold better than predicted from simple additive binding energy arguments, yet analogues possessing combinations of similar phenyl and quinazoline substituents do not show this ''supra-additive'' effect. Because some substituents which are mildly deactivating by themselves can be strongly activating when used in the correct combinations, it is proposed that certain substituted analogues possess the ability to induce a change in the conformation of the receptor when they bind. There is some bulk tolerance for substitution in the 6- and 7-positions of the quinazoline, so that 32 is not the optimal inhibitor for the induced conformation. The diethoxy derivative 56 [4-(3-bromoanilino)-6,7-diethoxyquinazoline] shows an IC50 Of 0.006 nM, making it the most potent inhibitor of the tyrosine kinase activity of the EGFR yet reported.