4-amino-6-[1-(3-fluoro-benzyl)-1H-indazol-5-ylamino]-pyrimidine-5-carbaldehyde | 1021942-18-6

• 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: 4-amino-6-[1-(3-fluoro-benzyl)-1H-indazol-5-ylamino]-pyrimidine-5-carbaldehyde
• 英文别名: 4-amino-6-[[1-[(3-fluorophenyl)methyl]indazol-5-yl]amino]pyrimidine-5-carbaldehyde
• CAS: 1021942-18-6
• 化学式: C₁₉H₁₅FN₆O
• 分子量: 362.366
• InChiKey: CEFIYYCIBJYHLH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  27
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.05
• 拓扑面积：
  98.7
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  4-amino-6-[1-(3-fluoro-benzyl)-1H-indazol-5-ylamino]-pyrimidine-5-carbaldehyde 在 盐酸羟胺 作用下， 以 甲醇 为溶剂， 生成 4-amino-6-[1-(3-fluoro-benzyl)-1H-indazol-5-ylamino]-pyrimidine-5-carbaldehyde oxime
  参考文献：
  名称：

  Discovery of novel 4-amino-6-arylaminopyrimidine-5-carbaldehyde oximes as dual inhibitors of EGFR and ErbB-2 protein tyrosine kinases

  摘要：

  We herein disclose a novel series of 4-aminopyrimidine-5-carbaldehyde oximes that are potent and selective inhibitors of both EGFR and ErbB-2 tyrosine kinases, with IC50 values in the nanomolar range. Structure-activity relationship (SAR) studies elucidated a critical role for the 4-amino and C-6 arylamino moieties. The X-ray co-crystal structure of EGFR with 37 was determined and validated our design rationale. (C) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2008.05.024
• 作为产物：
  描述：

  4-氨基-6-氯-5-醛基嘧啶 、 5-氨基-1-(3-氟苄基)吲唑 在 N,N-二异丙基乙胺 作用下， 以 二甲基亚砜 为溶剂， 反应 2.0h， 生成 4-amino-6-[1-(3-fluoro-benzyl)-1H-indazol-5-ylamino]-pyrimidine-5-carbaldehyde
  参考文献：
  名称：

  HYDRAZONE DERIVATIVES AS KINASE INHIBITORS

  摘要：

  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。

  公开号：

  US20080114004A1

文献信息

• SUBSTITUTED PYRIMIDINYL OXIME KINASE INHIBITORS
  申请人：Xu Guozhang

  公开号：US20070270425A1

  公开（公告）日：2007-11-22

  The present invention is directed to substituted pyrimidine compounds of formula (I): and forms thereof, their synthesis and use for treating, preventing or ameliorating a chronic or acute protein kinase mediated disease, disorder or condition.

  本发明涉及公式（I）的取代嘧啶化合物及其形式，它们的合成和用于治疗、预防或改善慢性或急性蛋白激酶介导的疾病、疾病或病况。
• Substituted Pyrimidinyl Oxime Kinase Inhibitors
  申请人：Battista Kathleen A.

  公开号：US20120157412A1

  公开（公告）日：2012-06-21

  The present invention is directed to substituted pyrimidine compounds of formula (I): and forms thereof, their synthesis and use for treating, preventing or ameliorating a chronic or acute protein kinase mediated disease, disorder or condition.

  本发明涉及式(I)的取代嘧啶化合物及其形式，它们的合成和用于治疗、预防或改善慢性或急性蛋白激酶介导的疾病、紊乱或状况的用途。
• Hydrazone derivatives as kinase inhibitors
  申请人：Janssen Pharmaceutica NV

  公开号：US07893064B2

  公开（公告）日：2011-02-22

  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 R1, R2, R3 and R4 are as defined herein.

  本发明涉及公式（I）的新型双环嘧啶化合物或其形式或组合物，作为ATP-蛋白激酶相互作用的抑制剂，其中在公式（I）中亚胺甲基双键的两侧取代基可以处于E或Z构型；R1、R2、R3和R4如本文所定义。
• 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.
• US7893064B2
  申请人：——

  公开号：US7893064B2

  公开（公告）日：2011-02-22