6-{[(1R,2S)-2-aminocyclohexyl]amino}-5-cyano-2-(3-methylanilino)pyridine-3-carboxamide | 1374969-99-9

• 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: 6-{[(1R,2S)-2-aminocyclohexyl]amino}-5-cyano-2-(3-methylanilino)pyridine-3-carboxamide
• 英文别名: 6-{[(1R,2S)-2-aminocyclohexyl]amino}-5-cyano-2-[(3-methylphenyl)amino]pyridine-3-carboxamide；6-[[(1R,2S)-2-aminocyclohexyl]amino]-5-cyano-2-(3-methylanilino)pyridine-3-carboxamide
• CAS: 1374969-99-9
• 化学式: C₂₀H₂₄N₆O
• 分子量: 364.45
• InChiKey: XAMCCSYNPOEISO-DLBZAZTESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  27
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  130
• 氢给体数：
  4
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  6-{[(1R,2S)-2-aminocyclohexyl]amino}-5-cyano-2-(3-methylanilino)pyridine-3-carboxamide 、 乙酸酐 在 吡啶 作用下， 以 二氯甲烷 为溶剂， 反应 0.5h， 以67%的产率得到6-{[(1R,2S)-2-acetamidocyclohexyl]amino}-5-cyano-2-(3-methylanilino)pyridine-3-carboxamide
  参考文献：
  名称：

  Discovery of Novel Pyrido-pyridazinone Derivatives as FER Tyrosine Kinase Inhibitors with Antitumor Activity

  摘要：

  To obtain a new anticancer drug, we focused on FER tyrosine kinase. Starting with high-throughput screening with our in-house chemical library, compound 1, which has a pyridine moiety, was found. Referring to their X-ray crystal structure with FES proto-oncogene tyrosine kinase, as a surrogate of FER followed by chemical modification including scaffold hopping of the pyridine template, we discovered pyrido-pyridazinone derivatives with potent FER kinase inhibitory activity. Here, we disclose the structure-activity relationship on the scaffold and representative compound 21 (DS21360717), which showed in vivo antitumor efficacy in a subcutaneous tumor model.

  DOI：

  10.1021/acsmedchemlett.8b00631
• 作为产物：
  描述：

  tert-butyl [(1S,2R)-2-{[5-carbamoyl-3-cyano-6-(3-methylanilino)pyridin-2-yl]amino}cyclohexyl]carbamate 在 盐酸 作用下， 以 乙醇 为溶剂， 以100%的产率得到6-{[(1R,2S)-2-aminocyclohexyl]amino}-5-cyano-2-(3-methylanilino)pyridine-3-carboxamide
  参考文献：
  名称：

  Discovery of Novel Pyrido-pyridazinone Derivatives as FER Tyrosine Kinase Inhibitors with Antitumor Activity

  摘要：

  To obtain a new anticancer drug, we focused on FER tyrosine kinase. Starting with high-throughput screening with our in-house chemical library, compound 1, which has a pyridine moiety, was found. Referring to their X-ray crystal structure with FES proto-oncogene tyrosine kinase, as a surrogate of FER followed by chemical modification including scaffold hopping of the pyridine template, we discovered pyrido-pyridazinone derivatives with potent FER kinase inhibitory activity. Here, we disclose the structure-activity relationship on the scaffold and representative compound 21 (DS21360717), which showed in vivo antitumor efficacy in a subcutaneous tumor model.

  DOI：

  10.1021/acsmedchemlett.8b00631

文献信息

• BENZAMIDES AND NICOTINAMIDES AS SYK MODULATORS
  申请人：Jia Zhaozhong J.

  公开号：US20120142671A1

  公开（公告）日：2012-06-07

  The present invention is directed to compounds of formula I and pharmaceutically acceptable salts, esters, and prodrugs thereof which are inhibitors of Syk kinase. The present invention is also directed to intermediates used in making such compounds, the preparation of such a compound, pharmaceutical compositions containing such a compound, methods of inhibition Syk kinase activity, methods of inhibition the platelet aggregation, and methods to prevent or treat a number of conditions mediated at least in part by Syk kinase activity, such as Non Hodgkin's Lymphoma.

  本发明涉及公式I的化合物及其药学上可接受的盐、酯和前药，这些化合物是Syk激酶的抑制剂。本发明还涉及用于制备这些化合物的中间体，制备这种化合物的方法，含有这种化合物的药物组合物，抑制Syk激酶活性的方法，抑制血小板聚集的方法，以及预防或治疗至少部分由Syk激酶活性介导的多种疾病，如非霍奇金淋巴瘤的方法。
• US8846928B2
  申请人：——

  公开号：US8846928B2

  公开（公告）日：2014-09-30
• US9359375B2
  申请人：——

  公开号：US9359375B2

  公开（公告）日：2016-06-07
• US9902688B2
  申请人：——

  公开号：US9902688B2

  公开（公告）日：2018-02-27
• [EN] BENZAMIDES AND NICOTINAMIDES AS SYK MODULATORS<br/>[FR] BENZAMIDES ET NICOTINAMIDES EN TANT QUE MODULATEURS DE SYK
  申请人：PORTOLA PHARM INC

  公开号：WO2012061418A2

  公开（公告）日：2012-05-10

  The present invention is directed to compounds of formula I and pharmaceutically acceptable salts, esters, and prodrugs thereof which are inhibitors of Syk kinase. The present invention is also directed to intermediates used in making such compounds, the preparation of such a compound, pharmaceutical compositions containing such a compound, methods of inhibition Syk kinase activity, methods of inhibition the platelet aggregation, and methods to prevent or treat a number of conditions mediated at least in part by Syk kinase activity, such as Non Hodgkin's Lymphoma.