5-氯-4,6-二羟基-3-羧酸乙酯 | 846541-71-7

• 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
• 中文名称: 5-氯-4,6-二羟基-3-羧酸乙酯
• 中文别名: 5-氯-4,6-二羟基烟酸乙酯
• 英文名称: ethyl 5-chloro-4,6-dihydroxynicotinate
• 英文别名: 5-chloro-4,6-dihydroxy-nicotinic acid ethyl ester；5-Chlor-4,6-dihydroxy-nicotinsaeure-aethylester；5-Chloro-4,6-dihydroxynicotinic acid ethyl ester；ethyl 5-chloro-4-hydroxy-6-oxo-1H-pyridine-3-carboxylate
• CAS: 846541-71-7
• 化学式: C₈H₈ClNO₄
• 分子量: 217.609
• InChiKey: SEFFUTOCCLZPNV-UHFFFAOYSA-N

物化性质

• 熔点：
  257-258 °C
• 沸点：
  314.5±42.0 °C(Predicted)
• 密度：
  1.49±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  14
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  75.6
• 氢给体数：
  2
• 氢受体数：
  4

安全信息

• 海关编码：
  2933399090

反应信息

• 作为反应物：
  描述：

  5-氯-4,6-二羟基-3-羧酸乙酯 在 sodium hydroxide 、 TEA 、 sodium hydride 、 lithium hexamethyldisilazane 、 三氯氧磷 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 、 正己烷 为溶剂， 反应 21.5h， 生成 methyl 4-(4-bromo-2-chlorophenylamino)-5-chloro-6-methoxynicotinate
  参考文献：
  名称：

  Potent and Selective Mitogen-Activated Protein Kinase Kinase (MEK) 1,2 Inhibitors. 1. 4-(4-Bromo-2-fluorophenylamino)-1- methylpyridin-2(1H)-ones

  摘要：

  The role of MEK 1,2 in cancer tumorgenesis has been clearly demonstrated preclinically, and two selective inhibitors are currently undergoing clinical evaluation to determine their role in the human disease. We have discovered 4-(4-bromo-2-fluorophenylamino)-1-methylpyridin-2(1H)-ones as a new class of ATP noncompetitive MEK inhibitors. These inhibitors exhibit excellent cellular potency and good pharmacokinetic properties and have demonstrated the ability to inhibit ERK phosphorylation in HT-29 tumors from mouse xenograft studies.

  DOI：

  10.1021/jm050834y
• 作为产物：
  描述：

  4,6-二羟基烟酸乙酯 在 N-氯代丁二酰亚胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 72.0h， 生成 5-氯-4,6-二羟基-3-羧酸乙酯
  参考文献：
  名称：

  Potent and Selective Mitogen-Activated Protein Kinase Kinase (MEK) 1,2 Inhibitors. 1. 4-(4-Bromo-2-fluorophenylamino)-1- methylpyridin-2(1H)-ones

  摘要：

  The role of MEK 1,2 in cancer tumorgenesis has been clearly demonstrated preclinically, and two selective inhibitors are currently undergoing clinical evaluation to determine their role in the human disease. We have discovered 4-(4-bromo-2-fluorophenylamino)-1-methylpyridin-2(1H)-ones as a new class of ATP noncompetitive MEK inhibitors. These inhibitors exhibit excellent cellular potency and good pharmacokinetic properties and have demonstrated the ability to inhibit ERK phosphorylation in HT-29 tumors from mouse xenograft studies.

  DOI：

  10.1021/jm050834y

文献信息

• Heterocyclic inhibitors of MEK and methods of use thereof
  申请人：Wallace Eli

  公开号：US20050054701A1

  公开（公告）日：2005-03-10

  Disclosed are compounds of the Formula I and pharmaceutically acceptable salts and prodrugs thereof, wherein R 1 , R 2 , R 7 , R 8 , R 9 and R 10 , W and Y are as defined in the specification. Such compounds are MEK inhibitors and useful in the treatment of hyperproliferative diseases, such as cancer and inflammation, in mammals. Also disclosed are methods of using such compounds in the treatment of hyperproliferative diseases in mammals and pharmaceutical compositions containing such compounds.

  揭示了Formula I的化合物及其药用盐和前药，其中R1、R2、R7、R8、R9和R10、W和Y如规范中所定义。这些化合物是MEK抑制剂，在哺乳动物中用于治疗高增殖性疾病，如癌症和炎症。还公开了在哺乳动物中使用这些化合物治疗高增殖性疾病的方法以及含有这些化合物的药物组合物。
• NICOTINAMIDES AS JAK KINASE MODULATORS
  申请人：Bauer Shawn M.

  公开号：US20120108566A1

  公开（公告）日：2012-05-03

  The present invention is directed to compounds of formula I and pharmaceutically acceptable salts, esters, and prodrugs thereof which are inhibitors of JAK 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 JAK kinase activity, methods of inhibition the platelet aggregation, and methods to prevent or treat a number of conditions mediated at least in part by JAK kinase activity, such as undesired thrombosis and Non Hodgkin's Lymphoma.

  本发明涉及具有公式I的化合物及其药用可接受的盐、酯和前药，这些化合物是JAK激酶的抑制剂。本发明还涉及用于制备这类化合物的中间体，该化合物的制备，含有该化合物的药物组合物，抑制JAK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JAK激酶活性介导的多种疾病条件的方法，例如不良血栓形成和非霍奇金淋巴瘤。
• Method of treating inflammatory diseases
  申请人：Koch Kevin

  公开号：US20060030610A1

  公开（公告）日：2006-02-09

  Disclosed are methods of treating inflammatory diseases and disorders, such as arthritis and inflammatory bowel disease, in mammals.

  本发明涉及一种治疗哺乳动物的炎症性疾病和疾病的方法，例如关节炎和炎症性肠病的方法。
• Nicotinamides as JAK kinase modulators
  申请人：Bauer Shawn M.

  公开号：US09102625B2

  公开（公告）日：2015-08-11

  The present invention is directed to compounds of formula I and pharmaceutically acceptable salts, esters, and prodrugs thereof which are inhibitors of JAK 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 JAK kinase activity, methods of inhibition the platelet aggregation, and methods to prevent or treat a number of conditions mediated at least in part by JAK kinase activity, such as undesired thrombosis and Non Hodgkin's Lymphoma.

  本发明涉及化合物I的制备及其药物可接受的盐、酯和前药，这些化合物是JAK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，含有这种化合物的制药组合物，抑制JAK激酶活性的方法，抑制血小板聚集的方法，以及预防或治疗由JAK激酶活性至少部分介导的多种情况，如不良血栓形成和非霍奇金淋巴瘤的方法。
• den Hertog et al., Recueil des Travaux Chimiques des Pays-Bas, 1950, vol. 69, p. 673,690
  作者：den Hertog et al.

  DOI：——

  日期：——