3-(2,6-Dichlorophenyl)-1,6-naphthyridine-2,7-diamine | 179342-45-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: 3-(2,6-Dichlorophenyl)-1,6-naphthyridine-2,7-diamine
• 英文别名: 3-(2,6-Dichlorophenyl)-[1,6]-naphthyridine-2,7-diamine；2,7-diamino-3-(2,6-dichlorophenyl)-[1,6]naphthyridine
• CAS: 179342-45-1
• 化学式: C₁₄H₁₀Cl₂N₄
• 分子量: 305.166
• InChiKey: RFCMDTOLDNJWEN-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：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  77.8
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3-(2,6-Dichlorophenyl)-1,6-naphthyridine-2,7-diamine 在 氟化氢吡啶 、 sodium nitrite 作用下， 反应 2.5h， 以75%的产率得到3-(2,6-Dichlorophenyl)-7-fluoro-1,6-naphthyridin-2-amine
  参考文献：
  名称：

  Synthesis of 7-substituted 3-aryl-1,6-naphthyridin-2-amines and 7-substituted 3-aryl-1,6-naphthyridin-2(1H )-ones via diazotization of 3-aryl-1,6-naphthyridine-2,7-diamines

  摘要：

  由3-芳基-1重氮化制备3-芳基-7-卤代-1,6-萘啶-2-胺和3-芳基-7-卤代-1,6-萘啶-2(1H)-酮报道了 ,6-萘啶-2,7-二胺。在各种溶剂（浓 HCl、50% HBF4、70% HF-吡啶、20% 和 90% H2SO4、稀 HCl 和纯 TFA）中研究了反应。通过适当选择溶剂和其他条件，可以获得目标化合物的良好产率，尽管在某些情况下也会产生各种不同的副产物。随后用烷基胺取代 7-卤素取代基提供了获得更复杂的 7-取代 1,6-萘啶衍生物的途径，这些衍生物是潜在的酪氨酸激酶抑制剂。

  DOI：

  10.1039/b002599m
• 作为产物：
  描述：

  乙二醇乙醚 、 2,6-二氯苯乙腈 、 4,6-二氨基-3-吡啶甲醛 在 sodium 作用下， 反应 0.5h， 生成 3-(2,6-Dichlorophenyl)-1,6-naphthyridine-2,7-diamine 、 2,6-二氯苯基乙酰胺 、 7-amino-2-[(2,6-dichlorophenyl)methyl]pyrido[4,3-d]pyrimidine 、 3-[2-chloro-6-(2-ethoxyethoxy)phenyl]-1,6-naphthyridine-2,7-diamine
  参考文献：
  名称：

  作为pp60（c-src）选择性抑制剂的7-取代的3-（2,6-二氯苯基）-1,6-萘吡啶-2（1H）-one的合成与构效关系。

  摘要：

  7-取代的3-（2,6-二氯苯基）-1,6-萘啶-2（1H）-ones是有效的蛋白酪氨酸激酶抑制剂，对c-Src具有选择性。化合物的制备方法是：将4，6-二氨基乙醛与2，6-二氯苯基乙腈缩合，并通过在50％氟硼酸水溶液中进行长时间的重氮化，分别将产物的2-和7-氨基分别转化为羟基和氟代。N-甲基化，然后用脂族二胺，芳族胺或其衍生的锂阴离子处理，得到所需化合物。为了评估相关吡啶并[2,3-d]嘧啶-7（8H）-的两个环A氮杂原子对化合物的相对贡献，还制备了所选的异构体1，8-萘啶-2（1H）-对。抑制活性。评价了化合物通过c-Src，FGF-1受体和PDGF-β受体酶防止模型底物磷酸化的能力。总体而言，针对不同激酶的活性具有高度相关性，其中c-Src通常对结构变化最敏感。1，带有基本脂肪族侧链的6-萘啶-2（1H）-one类似物[7-NH（CH（2））（n）（）NRR，7-NHPhO（CH（

  DOI：

  10.1021/jm000148t

文献信息

• Naphthyridinones for inhibiting protein tyrosine kinase and cell cycle
  申请人：Warner-Lambert Company

  公开号：US06150359A1

  公开（公告）日：2000-11-21

  This invention relates to the inhibition of protein tyrosine kinase (PTK) and cell cycle kinase mediated cellular proliferation. More specifically, this invention relates to naphthyridinones and their use in inhibiting cellular proliferation and PTK or cell cycle kinase enzymatic activity.

  这项发明涉及抑制蛋白酪氨酸激酶（PTK）和细胞周期激酶介导的细胞增殖。更具体地说，这项发明涉及萘啶酮及其在抑制细胞增殖和PTK或细胞周期激酶酶活性中的用途。
• 3-(3,5-Dimethoxyphenyl)-1,6-naphthyridine-2,7-diamines and Related 2-Urea Derivatives Are Potent and Selective Inhibitors of the FGF Receptor-1 Tyrosine Kinase
  作者：Andrew M. Thompson、Cleo J. C. Connolly、James M. Hamby、Stacey Boushelle、Brian G. Hartl、Aneesa M. Amar、Alan J. Kraker、Denise L. Driscoll、Randall W. Steinkampf、Sandra J. Patmore、Patrick W. Vincent、Bill J. Roberts、William L. Elliott、Wayne Klohs、Wilbur R. Leopold、H. D. Hollis Showalter、William A. Denny

  DOI：10.1021/jm000161d

  日期：2000.11.1

  A series of 3-aryl-1,6-naphthyridine-2, 7-diamines and related 2-ureas were prepared and evaluated as inhibitors of the FGF receptor-1 tyrosine kinase. Condensation of 4,6-diamino-nicotinaldehyde and substituted phenylacetonitriles gave intermediate naphthyridine-2,7-diamines, and direct reaction of the monoanion of these (NaH/DMF) with alkyl or aryl isocyanates selectively gave the 2-ureas in varying yields (23-93%). For the preparation of more soluble 7-alkylamino-2-ureas, a number of protecting groups for the 2-amine were evaluated (phthaloyl, 4-methoxybenzyl) following selective blocking of the 7-amine (trityl), but these were not superior to the (required) 2-tert-Bu-urea group itself. Direct alkylation of the anion of the (unprotected) 7-amino group with excess 4-(3-chloropropyl)morpholine in DMF gave low (10%) yields of the desired product, but alkylation of the 7-acetamido anion, followed by mild alkaline hydrolysis, raised this to 64%. 3-Phenyl analogues were nonspecific inhibitors of isolated c-Src, FGFR, and PDGFR tyrosine kinases, whereas 3-(2,6-dichlorophenyl) analogues were most effective against c-Src and FGFR, and 3-(3,5-dimethoxyphenyl) derivatives showed high selectivity for FGFR alone. A water-soluble (7-morpholinylpropyl amino) analogue retained high FGFR potency (IC50 31 nM) and selectivity. Pairwise comparison of the 1,6-naphthyridines and the corresponding known pyrido[2,3-d]pyrimidine analogues showed little differences in potency or patterns of selectivity, suggesting that the 1-aza atom of the latter is not important for activity. A 7-acetamide derivative inhibited the growth of FGFR-expressing tumor cell lines and was particularly potent against HUVECs (IC50 4 nM). This compound was also a very potent inhibitor of HUVEC microcapillary formation (IC50 0.01 nM) and Matrigel invasion (IC50 7 nM) and showed significant in vivo antitumor effects in a highly vascularized mammary adenocarcinoma 16/c model at nontoxic doses. The compounds are worthy of further evaluation as antiangiogenesis agents.
• 6-ARYL PYRIDO[2,3-d]PYRIMIDINES AND NAPHTHYRIDINES FOR INHIBITING PROTEIN TYROSINE KINASE MEDIATED CELLULAR PROLIFERATION
  申请人：WARNER-LAMBERT COMPANY

  公开号：EP0790997B1

  公开（公告）日：2000-03-22
• US5733913A
  申请人：——

  公开号：US5733913A

  公开（公告）日：1998-03-31
• US5952342A
  申请人：——

  公开号：US5952342A

  公开（公告）日：1999-09-14