N⁴-(3-bromo-4-chlorophenyl)pyrido[3,4-d]pyrimidine-4,6-diamine | 2135696-75-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶并嘧啶类
• 英文名称: N⁴-(3-bromo-4-chlorophenyl)pyrido[3,4-d]pyrimidine-4,6-diamine
• 英文别名: N4-(3-bromo-4-chlorophenyl)pyrido[3,4-d]pyrimidine-4,6-diamine；4-N-(3-bromo-4-chlorophenyl)pyrido[3,4-d]pyrimidine-4,6-diamine
• CAS: 2135696-75-0
• 化学式: C₁₃H₉BrClN₅
• 分子量: 350.605
• InChiKey: IEWDHQAQUHRRPT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  20
• 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：
  76.7
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  二乙基磷乙酸 、 N⁴-(3-bromo-4-chlorophenyl)pyrido[3,4-d]pyrimidine-4,6-diamine 在 1-丙基磷酸酐 、 三乙胺 作用下， 以 乙酸乙酯 为溶剂， 反应 16.0h， 以88.5%的产率得到diethyl (2-((4-((3-bromo-4-chlorophenyl)amino)pyrido[3,4-d]pyrimidin-6-yl)amino)-2-oxoethyl)phosphonate
  参考文献：
  名称：

  [EN] USE OF QUINAZOLINE-BASED TYROSINE KINASE INHIBITORS FOR THE TREATMENT OF CANCERS WITH NRG1 FUSIONS
  [FR] UTILISATION D'INHIBITEURS DE TYROSINE KINASE À BASE DE QUINAZOLINE POUR TRAITER DES CANCERS AVEC FUSIONS DU GÈNE NRG1

  摘要：

  本文提供了选择癌症患者接受基于喹唑啉的酪氨酸激酶抑制剂治疗的方法，可以单独使用或与抗HER2/HER3抗体结合使用，以及治疗所选癌症患者的方法。如果患者的癌症具有NRG1融合，就会选择这些癌症患者接受治疗。然后，选择的患者将接受基于喹唑啉的酪氨酸激酶抑制剂单独使用或与抗HER2/HER3抗体结合使用。

  公开号：

  WO2021155144A1
• 作为产物：
  描述：

  4-氯-6-氟吡啶并[3,4-D]嘧啶 在 三氟乙酸 作用下， 以 二氯甲烷 、 N,N-二甲基乙酰胺 、 二甲基亚砜 为溶剂， 反应 48.0h， 生成 N⁴-(3-bromo-4-chlorophenyl)pyrido[3,4-d]pyrimidine-4,6-diamine
  参考文献：
  名称：

  [EN] USE OF QUINAZOLINE-BASED TYROSINE KINASE INHIBITORS FOR THE TREATMENT OF CANCERS WITH NRG1 FUSIONS
  [FR] UTILISATION D'INHIBITEURS DE TYROSINE KINASE À BASE DE QUINAZOLINE POUR TRAITER DES CANCERS AVEC FUSIONS DU GÈNE NRG1

  摘要：

  本文提供了选择癌症患者接受基于喹唑啉的酪氨酸激酶抑制剂治疗的方法，可以单独使用或与抗HER2/HER3抗体结合使用，以及治疗所选癌症患者的方法。如果患者的癌症具有NRG1融合，就会选择这些癌症患者接受治疗。然后，选择的患者将接受基于喹唑啉的酪氨酸激酶抑制剂单独使用或与抗HER2/HER3抗体结合使用。

  公开号：

  WO2021155144A1

文献信息

• [EN] HETEROCYCLIC INHIBITORS OF TYROSINE KINASE<br/>[FR] INHIBITEURS HÉTÉROCYCLIQUES DE TYROSINE KINASE
  申请人：UNIV TEXAS

  公开号：WO2020219906A1

  公开（公告）日：2020-10-29

  The present disclosure relates to heterocyclic compounds and methods which may be useful as inhibitors of HER2 or EGFR for the treatment or prevention of disease, including cancer.

  本公开涉及杂环化合物和方法，这些方法可能作为HER2或EGFR的抑制剂，用于治疗或预防疾病，包括癌症。
• KINASE INHIBITORS, PRODRUG FORMS THEREOF AND THEIR USE IN THERAPY
  申请人：Smaill Jeffrey Bruce

  公开号：US20120202832A1

  公开（公告）日：2012-08-09

  The invention provides kinase inhibitors of Formula I: wherein either: (1) R 1 is H, and (a) R 2 is (3-chlorobenzyl)oxy- and R 3 is chloro; (b) R 2 and R 3 , together with the carbon atoms to which they are attached, form 1-(3-fluorobenzyl)-1H-pyrazole; (c) R 2 is 2-pyridinylmethoxy and R 3 is chloro; (d) R 2 and R 3 are both chloro; (e) R 2 is chloro and R 1 is bromo; (f) R 2 and R 3 are both bromo; (g) R 2 is fluoro and R 3 is ethynyl; (h) R 2 is chloro and R 3 is ethynyl; (i) R 2 is bromo and R 3 is ethynyl; (j) other than when R 1 is in the 3-position in combination with R 3 , in the 4-position, R 2 is bromo and R 3 is fluoro; (k) R 2 is 2-pyridinylmethoxy and R 3 is fluoro; or (l) R 2 is 2-pyridinylmethoxy and R 1 is bromo; or (2) at least one of R 1 , R 2 and R 3 is selected from benzyloxy, 3-chlorobenzyloxy and 2-pyridinylmethoxy and when at least one of R 1 , R 2 and R 3 is not benzyloxy, 3-chlorobenzyloxy or 2-pyridinylmethoxy, each of the others is independently selected from H, halogen, and C 2 -C 4 alkynyl, with the proviso that when one of R 1 , R 2 and R 3 is benzyloxy or 2-pyridinylmethoxy, the other two of R 1 , R 2 and R 3 are not H; or (3) two of R 1 , R 2 and R 3 , together with the carbon atoms to which they are attached, form 1-(3-fluorobenzyl)-1H-pyrazole; and the other is selected from H, halogen and C 2 -C 4 alkynyl. Also provided are reductive prodrugs, comprising a kinase inhibitor as defined above and a reductive trigger linked directly or indirectly to a nitrogen of the kinase inhibitor. Further provided are pharmaceutical compositions, comprising the kinase inhibitors or the prodrugs, and the use of such compositions in therapy, in particular for treating cancer.

  本发明提供了式I的激酶抑制剂：其中：(1) R1为H，且(a) R2为(3-氯苯基)氧基，R3为氯；(b) R2和R3与它们连接的碳原子一起形成1-(3-氟苯基)-1H-吡唑；(c) R2为2-吡啶甲氧基，R3为氯；(d) R2和R3均为氯；(e) R2为氯，R1为溴；(f) R2和R3均为溴；(g) R2为氟，R3为乙炔基；(h) R2为氯，R3为乙炔基；(i) R2为溴，R3为乙炔基；(j) 当R1与R3组合时，R1在3位，R2在4位，R2为溴，R3为氟，除外；(k) R2为2-吡啶甲氧基，R3为氟；或(l) R2为2-吡啶甲氧基，R1为溴；或(2) R1、R2和R3中至少有一个选择自苄氧基、3-氯苯甲氧基和2-吡啶甲氧基，当R1、R2和R3中至少有一个不是苄氧基、3-氯苯甲氧基或2-吡啶甲氧基时，其他每个基团独立选择自H、卤素和C2-C4炔基，但当R1、R2和R3中有一个为苄氧基或2-吡啶甲氧基时，另外两个基团不为H；或(3) R1、R2和R3中的两个与它们连接的碳原子一起形成1-(3-氟苯基)-1H-吡唑；另外一个基团选择自H、卤素和C2-C4炔基。还提供了还原前药，包括定义如上的激酶抑制剂和直接或间接连接到激酶抑制剂的氮上的还原触发剂。还提供了制药组合物，包括激酶抑制剂或前药，以及在治疗中使用这种组合物，特别是用于治疗癌症。
• Kinase inhibitors, prodrug forms thereof and their use in therapy
  申请人：Smaill Jeffrey Bruce

  公开号：US09101632B2

  公开（公告）日：2015-08-11

  The invention provides kinase inhibitors of Formula I: wherein either: (1) R1 is H, and (a) R2 is (3-chlorobenzyl)oxy-and R3 is chloro; (b) R2 and R3, together with the carbon atoms to which they are attached, form 1-(3-fluorobenzyl)-1H-pyrazole; (c) R2 is 2-pyridinylmethoxy and R3 is chloro; (d) R2 and R3 are both chloro; (e) R2 is chloro and R1 is bromo; (f) R2 and R3 are both bromo; (g) R2 is fluoro and R3 is ethynyl; (h) R2 is chloro and R3 is ethynyl; (i) R2 is bromo and R3 is ethynyl; (j) other than when R1 is in the 3-position in combination with R3, in the 4-position, R2 is bromo and R3 is fluoro; (k) R2 is 2-pyridinylmethoxy and R3 is fluoro; or (l) R2 is 2-pyridinylmethoxy and R1 is bromo; or (2) at least one of R1, R2 and R3 is selected from benzyloxy, 3-chlorobenzyloxy and 2-pyridinylmethoxy and when at least one of R1, R2 and R3 is not benzyloxy, 3-chlorobenzyloxy or 2-pyridinylmethoxy, each of the others is independently selected from H, halogen, and C2-C4 alkynyl, with the proviso that when one of R1, R2 and R3 is benzyloxy or 2-pyridinylmethoxy, the other two of R1, R2 and R3 are not H; or (3) two of R1, R2 and R3, together with the carbon atoms to which they are attached, form 1-(3-fluorobenzyl)-1H-pyrazole; and the other is selected from H, halogen and C2-C4 alkynyl. Also provided are reductive prodrugs, comprising a kinase inhibitor as defined above and a reductive trigger linked directly or indirectly to a nitrogen of the kinase inhibitor. Further provided are pharmaceutical compositions, comprising the kinase inhibitors or the prodrugs, and the use of such compositions in therapy, in particular for treating cancer.

  本发明提供了Formula I的激酶抑制剂：其中要么：（1）R1为H，且（a）R2为（3-氯苯基）氧基且R3为氯；（b）R2和R3与它们附着的碳原子一起形成1-（3-氟苯基）-1H-吡唑；（c）R2为2-吡啶甲氧基且R3为氯；（d）R2和R3均为氯；（e）R2为氯且R1为溴；（f）R2和R3均为溴；（g）R2为氟且R3为乙炔基；（h）R2为氯且R3为乙炔基；（i）R2为溴且R3为乙炔基；（j）当R1与R3相结合时，不在3位，而在4位时，R2为溴且R3为氟；（k）R2为2-吡啶甲氧基且R3为氟；或（l）R2为2-吡啶甲氧基且R1为溴；或（2）至少有一个R1，R2和R3选自苄氧基，3-氯苯甲氧基和2-吡啶甲氧基，当至少有一个R1，R2和R3不是苄氧基，3-氯苯甲氧基或2-吡啶甲氧基时，其他每个都独立地选自H，卤素和C2-C4炔基，但是当R1，R2和R3中有一个是苄氧基或2-吡啶甲氧基时，其他两个不是H；或（3）两个R1，R2和R3与它们附着的碳原子一起形成1-（3-氟苯基）-1H-吡唑；另外还提供了还原型前药，包括定义如上的激酶抑制剂和与激酶抑制剂的氮直接或间接连接的还原性触发剂。还提供了制药组合物，包括激酶抑制剂或前药，以及这种组合物在治疗中的应用，特别是用于治疗癌症。