(1H-indazol-3-yl)-{2-[(isoquinolin-6-ylmethyl)-amino]-phenyl}-methanone | 821767-49-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (1H-indazol-3-yl)-{2-[(isoquinolin-6-ylmethyl)-amino]-phenyl}-methanone
• 英文别名: (1H-Indazol-3-yl)(2-{[(isoquinolin-6-yl)methyl]amino}phenyl)methanone；1H-indazol-3-yl-[2-(isoquinolin-6-ylmethylamino)phenyl]methanone
• CAS: 821767-49-1
• 化学式: C₂₄H₁₈N₄O
• 分子量: 378.433
• InChiKey: UAVAQFBWBVCGMG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.4
• 重原子数：
  29
• 可旋转键数：
  5
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.04
• 拓扑面积：
  70.7
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  1H-indazol-3-yl-[2-(isoquinolin-6-ylmethylideneamino)phenyl]methanone 在 sodium cyanoborohydride 作用下， 以 甲醇 为溶剂， 反应 48.0h， 生成 (1H-indazol-3-yl)-{2-[(isoquinolin-6-ylmethyl)-amino]-phenyl}-methanone
  参考文献：
  名称：

  Synthesis and evaluation of heteroaryl-ketone derivatives as a novel class of VEGFR-2 inhibitors

  摘要：

  We have discovered novel inhibitors of VEGFR-2 kinase with low nanomolar potency in both enzymatic and cell-based assays. Active series are heteroaryl-ketone compounds containing a central aromatic ring with either an indazolyl or indolyl keto group in the ortho orientation to the benzylic amine group (Fig. 1). The best compounds were demonstrated to be inactive against a small select panel of tyrosine and serine/threonine kinases with the exception of VEGFR-1 kinase, a close family member. In addition, the lead candidate 8 displayed acceptable exposure levels when administered orally to mice. (c) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2008.06.083

文献信息

• [EN] HETEROARYLAMINO-PHENYLKETONE DERIVATIVES AND THEIR USE AS KINASE INHIBITORS<br/>[FR] DERIVES D'HETEROARYLAMINO-PHENYLCETONE ET LEUR UTILISATION EN TANT QU'INHIBITEURS DE KINASES
  申请人：IMCLONE SYSTEMS INC

  公开号：WO2005000813A1

  公开（公告）日：2005-01-06

  The present invention relates to compounds that inhibit VEGF receptor tyrosine kinases, especially KDR, pharmaceutical compositions that contain such compounds, methods of treating VEGF receptor kinase-dependent diseases and conditions in mammals using such compounds and composition and methods for their manufacture.

  本发明涉及抑制VEGF受体酪氨酸激酶，特别是KDR的化合物，包含这种化合物的药物组合物，使用这种化合物和组合物治疗哺乳动物中依赖VEGF受体激酶的疾病和病况的方法，以及其制造方法。
• Synthesis and evaluation of heteroaryl-ketone derivatives as a novel class of VEGFR-2 inhibitors
  作者：Eugene L. Piatnitski Chekler、Reeti Katoch-Rouse、Alexander S. Kiselyov、Dan Sherman、Xiaohu Ouyang、Ki Kim、Ying Wang、Yaron R. Hadari、Jacqueline F. Doody

  DOI：10.1016/j.bmcl.2008.06.083

  日期：2008.8

  We have discovered novel inhibitors of VEGFR-2 kinase with low nanomolar potency in both enzymatic and cell-based assays. Active series are heteroaryl-ketone compounds containing a central aromatic ring with either an indazolyl or indolyl keto group in the ortho orientation to the benzylic amine group (Fig. 1). The best compounds were demonstrated to be inactive against a small select panel of tyrosine and serine/threonine kinases with the exception of VEGFR-1 kinase, a close family member. In addition, the lead candidate 8 displayed acceptable exposure levels when administered orally to mice. (c) 2008 Elsevier Ltd. All rights reserved.