4-<(3-bromophenyl)amino>-7-fluoroquinazoline | 198961-95-4

• 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: 4-<(3-bromophenyl)amino>-7-fluoroquinazoline
• 英文别名: N-(3-bromophenyl)-7-fluoroquinazolin-4-amine；4-[(3-bromophenyl)amino]-7-fluoroquinazoline
• CAS: 198961-95-4
• 化学式: C₁₄H₉BrFN₃
• 分子量: 318.148
• InChiKey: RKEKUEHWOSEQMZ-UHFFFAOYSA-N

物化性质

• 沸点：
  422.9±40.0 °C(Predicted)
• 密度：
  1.619±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  19
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  37.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  N-(3-氨丙基)吗啉 、 4-<(3-bromophenyl)amino>-7-fluoroquinazoline 以 二甲基亚砜 为溶剂， 反应 26.0h， 以78%的产率得到4-[(3-bromophenyl)amino]-7-[(3-morpholinopropyl)amino]quinazoline
  参考文献：
  名称：

  Irreversible inhibitors of tyrosine kinases

  摘要：

  本发明提供了一种不可逆抑制酪氨酸激酶的化合物。还提供了一种治疗癌症、再狭窄、动脉粥样硬化、子宫内膜异位症和牛皮癣的方法，以及包含一种不可逆抑制酪氨酸激酶的化合物的药物组合物。

  公开号：

  US06344459B1
• 作为产物：
  描述：

  7-氟-4-喹唑啉酮 在 盐酸 、 三氯氧磷 作用下， 以 异丙醇 为溶剂， 反应 1.0h， 生成 4-<(3-bromophenyl)amino>-7-fluoroquinazoline
  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

• [EN] IRREVERSIBLE INHIBITORS OF TYROSINE KINASES<br/>[FR] INHIBITEURS IRREVERSIBLES DE TYROSINE KINASES
  申请人：WARNER-LAMBERT COMPANY

  公开号：WO1997038983A1

  公开（公告）日：1997-10-23

  (EN) The present invention provides compounds that are irreversible inhibitors of tyrosine kinases. Also provided is a method of treating cancer, restenosis, atherosclerosis, endometriosis, and psoriasis and a pharmaceutical composition that comprises a compound that is an irreversible inhibitor of tyrosine kinases.(FR) La présente invention concerne des composés qui sont des inhibiteurs irréversibles de tyrosine kinases. L'invention, qui concerne également un traitement du cancer, de la resténose, de l'athérosclérose, de l'endométriose et du psoriasis, concerne en outre une spécialité pharmaceutique comprenant un composé qui est un inhibiteur irréversible de tyrosine kinases.

  (中文)本发明提供了一些不可逆酪氨酸激酶抑制剂化合物。还提供了一种治疗癌症、再狭窄、动脉粥样硬化、子宫内膜异位症和牛皮癣的方法，以及包含一种不可逆酪氨酸激酶抑制剂化合物的制药组合物。
• Pyrimido[5,4-d]pyrimidines derivatives as irreversible inhibitors of tyrosine kinases
  申请人：Warner-Lambert Company

  公开号：US07786131B2

  公开（公告）日：2010-08-31

  The present invention relates to pyrimido [5,4-d] pyrimidine compounds of Formula II or a pharmaceutically acceptable salt thereof, wherein Q is and X, E1, E2, E3, R6 and p are as defined herein. The compounds of this invention are irreversible inhibitors of tyrosine kinases and are useful in the treatment of cancer, atherosclerosis, restenosis, endometriosis and psoriasis.

  本发明涉及式II或其药学上可接受的盐的嘧啶并[5,4-d]嘧啶化合物，其中Q为，X、E1、E2、E3、R6和p如本文所定义。本发明的化合物是酪氨酸激酶的不可逆抑制剂，可用于治疗癌症、动脉粥样硬化、再狭窄、子宫内膜异位症和银屑病。
• IRREVERSIBLE INHIBITORS OF TYROSINE KINASES
  申请人：WARNER-LAMBERT COMPANY

  公开号：EP0892789B1

  公开（公告）日：2002-02-27
• QUINAZOLINE DERIVATIVES FOR THE TREATMENT OF HERPESVIRAL INFECTIONS
  申请人：GPC Biotech AG

  公开号：EP1673346A1

  公开（公告）日：2006-06-28
• Quinazoline derivatives for the treatment of herpesviral infections
  申请人：Herget Thomas

  公开号：US20070123537A1

  公开（公告）日：2007-05-31

  The present invention relates to phenyl-quinazolinyl-amine derivatives and pharmaceutically acceptable salts thereof and pharmaceutical compositions comprising at least one of these derivatives and/or pharmaceutically salts thereof, as well as the use of these derivatives for the prophylaxis and/or treatment of herpesviral induced infections, including opportunistic infections, especially for the prophylaxis and/or treatment of infections and diseases induced by HCMV.