N-[1-(3-fluoro-benzyl)-1H-indazol-5-yl]-5-[(2,2,2-trifluoro-ethyl)-hydrazonomethyl]-pyrimidine-4,6-diamine | 1054315-71-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并吡唑类
• 英文名称: N-[1-(3-fluoro-benzyl)-1H-indazol-5-yl]-5-[(2,2,2-trifluoro-ethyl)-hydrazonomethyl]-pyrimidine-4,6-diamine
• 英文别名: 4-N-[1-[(3-fluorophenyl)methyl]indazol-5-yl]-5-[(E)-(2,2,2-trifluoroethylhydrazinylidene)methyl]pyrimidine-4,6-diamine
• CAS: 1054315-71-7
• 化学式: C₂₁H₁₈F₄N₈
• 分子量: 458.421
• InChiKey: KVQIKILPEUOSQA-GESPGMLMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  33
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  106
• 氢给体数：
  3
• 氢受体数：
  11

反应信息

• 作为产物：
  描述：

  4-amino-6-[1-(3-fluoro-benzyl)-1H-indazol-5-ylamino]-pyrimidine-5-carbaldehyde 、 2,2,2-三氟乙基肼 以 甲醇 为溶剂， 生成 N-[1-(3-fluoro-benzyl)-1H-indazol-5-yl]-5-[(2,2,2-trifluoro-ethyl)-hydrazonomethyl]-pyrimidine-4,6-diamine
  参考文献：
  名称：

  4-Amino-6-arylamino-pyrimidine-5-carbaldehyde hydrazones as potent ErbB-2/EGFR dual kinase inhibitors

  摘要：

  Members of a novel class of 4-amino-6-arylamino-pyrimidine-5-carbaldehyde hydrazones were identified as potent dual ErbB-2/EGFR kinase inhibitors using concept-guided design approach. These compounds inhibited the growth of ErbB-2 over-expressing human tumor cell lines (BT474, N87, and SK-BR-3) in vitro. Compound 15 emerged as a key lead and showed significant ability to inhibit growth factor-induced receptor phosphorylation in SK-BR-3 cells (IC(50)=54 nM) and cellular proliferation in vitro (IC(50)=14, 58, and 58 nM for BT474, N87, and SK-BR-3 respectively). The X-ray co-crystal structure of EGFR with a close analog (17) was determined and validated our design rationale.

  DOI：

  10.1016/j.bmcl.2008.07.020

文献信息

• HYDRAZONE DERIVATIVES AS KINASE INHIBITORS
  申请人：Xu Guozhang

  公开号：US20080114004A1

  公开（公告）日：2008-05-15

  The present invention is directed to novel bicyclic pyrimidine compounds of Formula (I) or a form or composition thereof as inhibitors of ATP-protein kinase interactions, wherein substituents on each side of the iminomethyl double bond in Formula (I) may be in the E or Z configuration; and wherein R 1 , R 2 , R 3 and R 4 are as defined herein.

  本发明涉及一种新型的双环嘧啶化合物，其化学式为（I），或其形式或组合物，作为ATP-蛋白激酶相互作用的抑制剂，其中在化学式（I）中亚甲基双键的两侧的取代基可以是E或Z构型；R1、R2、R3和R4如本文中所定义。
• US7893064B2
  申请人：——

  公开号：US7893064B2

  公开（公告）日：2011-02-22
• [EN] HYDRAZONE DERIVATIVES AS KINASE INHIBITORS<br/>[FR] DÉRIVÉS D'HYDRAZONE EN TANT QU'INHIBITEURS DE KINASE
  申请人：JANSSEN PHARMACEUTICA NV

  公开号：WO2008054633A1

  公开（公告）日：2008-05-08

  [EN] The present invention is directed to novel bicyclic pyrimidine compounds of Formula (I or a form or com osition thereof as inhibitors of ATP-protein kinase interactions, wherein substituents on each side of the iminomethyl double bond in Formula (I) may be in the E or Z configuration; and wherein R₁, R₂, R₃ and R₄ are as defined herein.
  [FR] La présente invention concerne de nouveaux composés bicycliques de pyrimidine selon la formule (I), ou une forme ou une composition de ces composés, en tant qu'inhibiteurs des interactions ATP-protéine kinase, dans laquelle les substituants situés de chaque côté de la double liaison iminométhyle dans la formule (I) peuvent être à configuration E ou Z ; et dans laquelle R₁, R₂, R₃ et R₄ sont tels que définis ici.
• 4-Amino-6-arylamino-pyrimidine-5-carbaldehyde hydrazones as potent ErbB-2/EGFR dual kinase inhibitors
  作者：Guozhang Xu、Marta C. Abad、Peter J. Connolly、Michael P. Neeper、Geoffrey T. Struble、Barry A. Springer、Stuart L. Emanuel、Niranjan Pandey、Robert H. Gruninger、Mary Adams、Sandra Moreno-Mazza、Angel R. Fuentes-Pesquera、Steven A. Middleton

  DOI：10.1016/j.bmcl.2008.07.020

  日期：2008.8

  Members of a novel class of 4-amino-6-arylamino-pyrimidine-5-carbaldehyde hydrazones were identified as potent dual ErbB-2/EGFR kinase inhibitors using concept-guided design approach. These compounds inhibited the growth of ErbB-2 over-expressing human tumor cell lines (BT474, N87, and SK-BR-3) in vitro. Compound 15 emerged as a key lead and showed significant ability to inhibit growth factor-induced receptor phosphorylation in SK-BR-3 cells (IC(50)=54 nM) and cellular proliferation in vitro (IC(50)=14, 58, and 58 nM for BT474, N87, and SK-BR-3 respectively). The X-ray co-crystal structure of EGFR with a close analog (17) was determined and validated our design rationale.