6-amino-5-(1-(2,6-dichloro-3-fluorophenyl)ethoxy)-nicotinonitrile | 756508-98-2

• 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: 6-amino-5-(1-(2,6-dichloro-3-fluorophenyl)ethoxy)-nicotinonitrile
• 英文别名: 6-Amino-5-[1-(2,6-dichloro-3-fluoro-phenyl)-ethoxy]-nicotinonitrile；6-amino-5-[1-(2,6-dichloro-3-fluorophenyl)ethoxy]pyridine-3-carbonitrile
• CAS: 756508-98-2
• 化学式: C₁₄H₁₀Cl₂FN₃O
• 分子量: 326.157
• InChiKey: VIGFRDNZWPHYHT-UHFFFAOYSA-N

物化性质

• 沸点：
  459.7±45.0 °C(Predicted)
• 密度：
  1.46±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  21
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  71.9
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  6-amino-5-(1-(2,6-dichloro-3-fluorophenyl)ethoxy)-nicotinonitrile 在 硼烷 、 盐酸 作用下， 以 四氢呋喃 、 甲醇 、 水 为溶剂， 反应 5.0h， 以94%的产率得到5-aminomethyl-3-[1-(2,6-dichloro-3-fluoro-phenyl)-ethoxy]-pyridin-2-ylamine
  参考文献：
  名称：

  [EN] AMINOHETEROARYL COMPOUNDS AS PROTEIN KINASE INHIBITORS
  [FR] COMPOSES D'AMINOHETEROARYLE UTILISES EN TANT QU'INHIBITEURS DE PROTEINE KINASE

  摘要：

  公开号：

  WO2004076412A3
• 作为产物：
  描述：

  2,6-二氯-3-氟苯乙酮 在 1,1'-双(二苯基膦)二茂铁 、 tris-(dibenzylideneacetone)dipalladium(0) 、 N-溴代丁二酰亚胺(NBS) 、 lithium aluminium tetrahydride 、 铁粉 、 溶剂黄146 、 三苯基膦 、 偶氮二甲酸二乙酯 作用下， 以 四氢呋喃 、 乙醇 、 水 、 N,N-二甲基甲酰胺 、 甲苯 、 乙腈 为溶剂， 反应 11.75h， 生成 6-amino-5-(1-(2,6-dichloro-3-fluorophenyl)ethoxy)-nicotinonitrile
  参考文献：
  名称：

  Structure Based Drug Design of Crizotinib (PF-02341066), a Potent and Selective Dual Inhibitor of Mesenchymal–Epithelial Transition Factor (c-MET) Kinase and Anaplastic Lymphoma Kinase (ALK)

  摘要：

  Because of the critical roles of aberrant signaling in cancer, both c-MET and ALK receptor tyrosine kinases are attractive oncology targets for therapeutic intervention. The cocrystal structure of 3 (PHA-665752), bound to c-MET kinase domain, revealed a novel ATP site environment, which served as the target to guide parallel, multiattribute drug design. A novel 2-amino-5-aryl-3-benzyloxypyridine series was created to more effectively make the key interactions achieved with 3. In the novel series, the 2-aminopyridine core allowed a 3-benzyloxy group to reach into the same pocket as the 2,6-dichlorophenyl group of 3 via a more direct vector and thus with a better ligand efficiency (LE). Further optimization of the lead series generated the clinical candidate crizotinib (PF-02341066), which demonstrated potent in vitro and in vivo c-MET kinase and ALK inhibition, effective tumor growth inhibition, and good pharmaceutical properties.

  DOI：

  10.1021/jm2007613

文献信息

• Enantiomerically pure aminoheteroaryl compounds as protein kinase inhibitors
  申请人：Cui Jean Jingrong

  公开号：US20060046991A1

  公开（公告）日：2006-03-02

  Enantiomerically pure compound of formula 1 are provided, as well as methods for their synthesis and use. Preferred compounds are potent inhibitors of the c-Met protein kinase, and are useful in the treatment of abnormal cell growth disorders, such as cancers.

  提供了式1的对映纯化合物，以及它们的合成和使用方法。优选化合物是c-Met蛋白激酶的强效抑制剂，并且在治疗异常细胞生长紊乱，如癌症方面具有用处。
• [EN] AMINOHETEROARYL COMPOUNDS AS PROTEIN TYROSINE KINASE INHIBITORS<br/>[FR] COMPOSES AMINOHETEROARYLES EN TANT QU'INHIBITEURS DES PROTEINES TYROSINE KINASES
  申请人：PFIZER

  公开号：WO2006021886A1

  公开（公告）日：2006-03-02

  Aminoheteroaryl compounds are provided, as well as methods for their synthesis and use. Preferred compounds are potent inhibitors of the c-Met protein kinase, and are useful in the treatment of abnormal cell growth disorders, such as cancers.

  提供了氨基杂环芳基化合物，以及它们的合成和使用方法。优选化合物是c-Met蛋白激酶的强效抑制剂，并且在治疗异常细胞生长紊乱，如癌症方面具有用处。
• ENANTIOMERICALLY PURE AMINOHETEROARYL COMPOUNDS AS PROTEIN KINASE INHIBITORS
  申请人：CUI Jingrong Jean

  公开号：US20140288086A1

  公开（公告）日：2014-09-25

  Enantiomerically pure compound of formula 1 are provided, as well as methods for their synthesis and use. Preferred compounds are potent inhibitors of the c-Met protein kinase, and are useful in the treatment of abnormal cell growth disorders, such as cancers.

  本发明提供了公式1的对映纯化合物，以及它们的合成和使用方法。首选化合物是c-Met蛋白激酶的强效抑制剂，可用于治疗异常细胞增生性疾病，例如癌症。
• Aminoheteroaryl compounds as protein kinase inhibitors
  申请人：Cui Jean Jingrong

  公开号：US20050009840A1

  公开（公告）日：2005-01-13

  Aminopyridine and aminopyrazine compounds of formula (1), compositions including these compounds, and methods of their use are provided. Preferred compounds of formula 1 have activity as protein kinase inhibitors, including as inhibitors of c-MET.

  提供了公式（1）的氨基吡啶和氨基吡嗪化合物、包括这些化合物的组合物以及它们的使用方法。公式1的优选化合物具有作为蛋白激酶抑制剂的活性，包括作为c-MET的抑制剂。
• AGENT FOR PREVENTING AND/OR TREATING AMYOTROPHIC LATERAL SCLEROSIS
  申请人：Kyoto University

  公开号：EP3246046A1

  公开（公告）日：2017-11-22

  The present invention provides a prophylactic and/or therapeutic agent for amyotrophic lateral sclerosis (ALS), which contains one or more kinase inhibitors selected from the group consisting of an epithelial cell growth factor receptor (EGFR) inhibitor, a fibroblast growth factor receptor (FGFR) inhibitor, an Aurorakinase inhibitor, a protein kinase A (PKA) inhibitor, a protein kinase C (PKC) inhibitor, an MEK inhibitor, an Met inhibitor, a JNK inhibitor, a Syk inhibitor and a JAK inhibitor, a prostaglandin analogue and an estrogen receptor antagonist, or one or more kinase inhibitors selected from the group consisting of Tivozanib and an analog thereof, SB 216763, Cdk2 Inhibitor II, BUDESONIDE, RIBOFLAVIN, alpha-TOCHOPHEROL, AMODIAQUINE, SU9516, Sunitinib and an analog thereof, GSK-3 Inhibitor XIII, Bisindolylmaleimide I, HYDROQUINONE, FLUNISOLIDE, MGCD-265, Indirubin-3'-monoxime, HYDRASTINE (1R,9S), PIPERINE, BUTAMBEN, Axitinib and an analog thereof, APOMORPHINE, FENBUFEN, Bosutinib (SKI-606) and an analog thereof, a Wee1 Inhibitor, Cdk2 Inhibitor IV, NU6140, 3-hydroxybutyric acid, AT9283, Imatinib, Nilotinib, Rebastinib, and Bafetinib for the prophylaxis and/or treatment of ALS. Particularly, using a compound already on the market as a pharmaceutical product, a pharmaceutical product for the prophylaxis or treatment of ALS can be developed rapidly at a low cost.

  本发明提供了一种肌萎缩性脊髓侧索硬化症（ALS）的预防和/或治疗剂，它含有一种或多种激酶抑制剂，这些激酶抑制剂选自由上皮细胞生长因子受体（EGFR）抑制剂、成纤维细胞生长因子受体（FGFR）抑制剂、Aurorakinase抑制剂、蛋白激酶A（PKA）抑制剂、蛋白激酶C（PKC）抑制剂组成的组、成纤维细胞生长因子受体 (FGFR) 抑制剂、Aurorakinase 抑制剂、蛋白激酶 A (PKA) 抑制剂、蛋白激酶 C (PKC) 抑制剂、MEK 抑制剂、Met 抑制剂、JNK 抑制剂、Syk 抑制剂和 JAK 抑制剂、前列腺素类似物和雌激素受体拮抗剂、或一种或多种激酶抑制剂，这些激酶抑制剂选自以下组别：Tivozanib 及其类似物、SB 216763、Cdk2 抑制剂 II、BUDESONIDE、RIBOFLAVIN、alpha-TOCHOPHEROL、AMODIAQUINE、SU9516、Sunitinib 及其类似物、GSK-3 抑制剂 XIII、Bisindolylmaleimide I、HYDROQUINONE、FLUNISOLIDE、MGCD-265、吲哚啉-3'-monoxime、氢化胱氨酸 (1R,9S)、哌啶、布坦本、阿希替尼及其类似物、阿朴磷、芬布芬、博苏替尼 (SKI-606) 及其类似物、Wee1抑制剂、Cdk2抑制剂IV、NU6140、3-羟基丁酸、AT9283、伊马替尼、尼洛替尼、雷巴替尼和巴非替尼，用于预防和/或治疗ALS。特别是，利用已作为药品上市的化合物，可以低成本快速开发出预防或治疗 ALS 的药品。