N'-(6-chloropyridazin-3-yl)-2-(quinolin-6-yl)acetohydrazide | 1266237-83-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: N'-(6-chloropyridazin-3-yl)-2-(quinolin-6-yl)acetohydrazide
• 英文别名: N'-(6-Chloropyridazin-3-yl)-2-(quinolin-6-yl)acetohydrazide；N'-(6-chloropyridazin-3-yl)-2-quinolin-6-ylacetohydrazide
• CAS: 1266237-83-5
• 化学式: C₁₅H₁₂ClN₅O
• 分子量: 313.746
• InChiKey: VSHRKGLXEAWCKI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  22
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  79.8
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  N'-(6-chloropyridazin-3-yl)-2-(quinolin-6-yl)acetohydrazide 在 四(三苯基膦)钯 盐酸 作用下， 以 甲醇 、 溶剂黄146 、 N,N-二甲基甲酰胺 为溶剂， 反应 8.0h， 生成 1-(3-(quinolin-6-ylmethyl)-[1,2,4]triazolo[4,3-b]pyridazin-6-yl)ethanone
  参考文献：
  名称：

  [EN] HETEROCYCLIC OXIME COMPOUNDS
  [FR] COMPOSÉS D'OXIMES HÉTÉROCYCLIQUES

  摘要：

  该发明涉及公式(I)的化合物及其盐，其中取代基如规范中所定义；公式(I)的化合物用于治疗人体或动物体，特别是针对c-Met酪氨酸激酶介导的疾病或症状；公式(I)的化合物用于制造治疗此类疾病的药物；包含公式(I)的化合物的药物组合物，可选地与组合伙伴一起，并且用于制备公式(I)的化合物的方法。

  公开号：

  WO2011020861A1
• 作为产物：
  描述：

  对氨基苯乙酸 在 硫酸 、 iron(II) sulfate 、 硝基苯 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 5.5h， 生成 N'-(6-chloropyridazin-3-yl)-2-(quinolin-6-yl)acetohydrazide
  参考文献：
  名称：

  Lessons from (S)-6-(1-(6-(1-Methyl-1H-pyrazol-4-yl)-[1,2,4]triazolo[4,3-b]pyridazin-3-yl)ethyl)quinoline (PF-04254644), an Inhibitor of Receptor Tyrosine Kinase c-Met with High Protein Kinase Selectivity but Broad Phosphodiesterase Family Inhibition Leading to Myocardial Degeneration in Rats

  摘要：

  The hepatocyte growth factor (HGF)/c-Met signaling axis is deregulated in many cancers and plays important roles in tumor invasive growth and metastasis. An exclusively selective c-Met inhibitor (S)-6-(1-(6-(1-methyl-1H-pyrazol -4-yl) - [1,2,4] triazolo [4,3-b pyridazin- 3-yl) ethyl) quinoline (8) was discovered from a highly selective high-throughput screening hit. via structure-based drug design and medicinal chemistry lead optimization. Compound 8 had many attractive properties meriting preclinical evaluation. Broad off-target screens identified 8 as a pan-phosphodiesterase (PDE) family inhibitor, which was implicated in a sustained increase in heart rate, increased cardiac output, and decreased contractility indices, as well as myocardial degeneration in in vivo safety evaluations in rats. Compound 8 was terminated as a preclinical candidate because of a narrow therapeutic window in cardio-related safety. The learning from multiparameter lead optimization and strategies to avoid the toxicity attrition at the late stage of drug discovery are discussed.

  DOI：

  10.1021/jm400926x

文献信息

• [EN] HETEROCYCLIC HYDRAZONE COMPOUNDS AND THEIR USES TO TREAT CANCER AND INFLAMMATION<br/>[FR] COMPOSÉS HYDRAZONE HÉTÉROCYCLIQUES ET LEURS UTILISATIONS POUR TRAITER LE CANCER ET L'INFLAMMATION
  申请人：NOVARTIS AG

  公开号：WO2011018454A1

  公开（公告）日：2011-02-17

  The invention relates to compounds of formula (I) and salts thereof: wherein the substituents are as defined in the specification; a compound of formula (I) for use in the treatment of the human or animal body, in particular with regard to c-Met tyrosine kinase mediated diseases or conditions; the use of a compound of formula (I) for manufacturing a medicament for the treatment of such diseases; pharmaceutical compositions comprising a compound of the formula (I), optionally in the presence of a combination partner, and processes for the preparation of a compound of formula (I).

  该发明涉及公式(I)的化合物及其盐：其中取代基如规范中所定义；公式(I)的化合物用于治疗人体或动物体，特别是针对c-Met酪氨酸激酶介导的疾病或症状；公式(I)的化合物用于制造治疗此类疾病的药物；包含公式(I)的化合物的药物组合物，可选地与组合伙伴一起，并且公式(I)的化合物的制备方法。
• TRIAZOLOPYRIDAZINE PROTEIN KINASE MODULATORS
  申请人：Smith Christopher Ronald

  公开号：US20100120739A1

  公开（公告）日：2010-05-13

  The present disclosure relates to triazolopyridazine protein kinase modulators of Formula (I), methods of using these compounds to treat diseases mediated by kinase activity.

  本公开涉及式(I)的三唑并吡嗪蛋白激酶调节剂，以及使用这些化合物治疗由激酶活性介导的疾病的方法。
• HETEROCYCLIC OXIME COMPOUNDS
  申请人：DAI Miao

  公开号：US20110065708A1

  公开（公告）日：2011-03-17

  The invention relates to compounds of formula (I) and salts thereof: wherein the substituents are as defined in the specification; a compound of formula (I) for use in the treatment of the human or animal body, in particular with regard to c-Met tyrosine kinase mediated diseases or conditions; the use of a compound of formula (I) for manufacturing a medicament for the treatment of such diseases; pharmaceutical compositions comprising a compound of the formula (I), optionally in the presence of a combination partner, and processes for the preparation of a compound of formula (I).

  本发明涉及公式（I）的化合物及其盐： 其中取代基如规范中所定义；公式（I）的化合物用于人或动物体内的治疗，特别是针对c-Met酪氨酸激酶介导的疾病或情况；使用公式（I）的化合物制造治疗此类疾病的药物；包括公式（I）的化合物的制药组合物，可选地与联合伙伴一起使用，以及制备公式（I）的化合物的过程。
• HETEROCYCLIC HYDRAZONE COMPOUNDS
  申请人：He Feng

  公开号：US20120142681A1

  公开（公告）日：2012-06-07

  The invention relates to compounds of formula (I) and salts thereof: wherein the substituents are as defined in the specification; a compound of formula (I) for use in the treatment of the human or animal body, in particular with regard to c-Met tyrosine kinase mediated diseases or conditions; the use of a compound of formula (I) for manufacturing a medicament for the treatment of such diseases; pharmaceutical compositions comprising a compound of the formula (I), optionally in the presence of a combination partner, and processes for the preparation of a compound of formula (I).

  本发明涉及式（I）的化合物及其盐：其中取代基如说明书所定义；式（I）的化合物用于治疗人体或动物体，特别是涉及c-Met酪氨酸激酶介导的疾病或病症；使用式（I）的化合物制造用于治疗此类疾病的药物；包含式（I）的化合物的药物组合物，可选地与组合伙伴共存，以及制备式（I）的化合物的过程。
• Heterocyclic hydrazone compounds
  申请人：He Feng

  公开号：US08497368B2

  公开（公告）日：2013-07-30

  The invention relates to compounds of formula (I) and salts thereof: wherein the substituents are as defined in the specification; a compound of formula (I) for use in the treatment of the human or animal body, in particular with regard to c-Met tyrosine kinase mediated diseases or conditions; the use of a compound of formula (I) for manufacturing a medicament for the treatment of such diseases; pharmaceutical compositions comprising a compound of the formula (I), optionally in the presence of a combination partner, and processes for the preparation of a compound of formula (I).

  本发明涉及化合物的公式（I）及其盐：其中取代基的定义如规范中所述；化合物的公式（I）用于治疗人体或动物体，特别是与c-Met酪氨酸激酶介导的疾病或状况有关；化合物的公式（I）的用途用于制造用于治疗此类疾病的药物；包含化合物的公式（I）的制药组合物，可选择在合作伙伴的存在下，以及制备化合物的公式（I）的过程。