4,5,6-三氯烟酸 | 847608-28-0

• 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: 4,5,6-三氯烟酸
• 英文名称: 4,5,6-trichloronicotinic acid
• 英文别名: 4,5,6-trichloropyridine-3-carboxylic acid
• CAS: 847608-28-0
• 化学式: C₆H₂Cl₃NO₂
• 分子量: 226.446
• InChiKey: GDRLWCPMLULBNF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  12
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  50.2
• 氢给体数：
  1
• 氢受体数：
  3

安全信息

• 海关编码：
  2933399090

反应信息

• 作为反应物：
  描述：

  4,5,6-三氯烟酸 在 sodium hydride 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 乙醇 、 正己烷 为溶剂， 反应 17.0h， 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 sodium hydroxide 、 N-氯代丁二酰亚胺 、 TEA 、 三氯氧磷 作用下， 以 四氢呋喃 、 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 76.5h， 生成 4,5,6-三氯烟酸
  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

• Design, synthesis and pharmacological evaluation of bicyclic and tetracyclic pyridopyrimidinone analogues as new KRASG12C inhibitors
  作者：Xuanzheng Xiao、Mengzhen Lai、Zilan Song、Meiyu Geng、Jian Ding、Hua Xie、Ao Zhang

  DOI：10.1016/j.ejmech.2020.113082

  日期：2021.3

  clinical KRASG12C inhibitor AMG510, a scaffold hopping strategy was conducted including a F-OH cyclization approach and a pyridinyl N-atom working approach leading to new tetracyclic and bicyclic analogues. Compound 26a was identified possessing binding potency of 1.87 μM against KRASG12C and cell growth inhibition of 0.79 μM in MIA PaCa-2 pancreatic cancer cells. Treatment of 26a with NCI-H358 cells

  KRAS 是 RAS 家族中最常见改变的癌基因，尤其是 G12C 突变体 (KRAS G12C )，它已成为许多癌症的有前途的药物靶点。在首创临床KRAS G12C抑制剂AMG510的双环吡啶并嘧啶酮框架的基础上，进行了支架跳跃策略，包括F-OH环化方法和吡啶基N原子工作方法，从而产生新的四环和双环类似物。化合物26a经鉴定对 KRAS G12C具有 1.87 μM 的结合效力，并且在 MIA PaCa-2 胰腺癌细胞中具有 0.79 μM 的细胞生长抑制作用。用 NCI-H358 细胞处理26a导致 KRAS-GTP 水平下调以及下游 ERK 和 AKT 磷酸化的减少，呈剂量依赖性。分子对接表明26a的氟苯酚部分占据疏水口袋区域，从而与Arg68形成氢键。这些结果将有助于指导进一步的结构修饰。
• 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。
• 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。
• Novel Pyridine Compounds
  申请人：Bach Peter

  公开号：US20090227555A2

  公开（公告）日：2009-09-10

  The present invention relates to certain novel pyridin compounds of Formula (I) to processes for preparing such compounds, to their utility as P2Y12 inhibitors and as anti-thrombotic agents etc, and processes for their preparation, their use as medicaments in cardiovascular diseases as well as pharmaceutical compositions containing them.

  本发明涉及某些新型的Formula (I)吡啶化合物，以及制备这些化合物的方法，它们作为P2Y12抑制剂和抗血栓剂等的用途，以及它们的制备过程，它们在心血管疾病中作为药物的用途，以及包含它们的制药组合物。
• Pyridine Analogues
  申请人：Andersen Soren

  公开号：US20080312208A1

  公开（公告）日：2008-12-18

  The present invention relates to certain new pyridin analogues of Formula (I) Chemical formula should be inserted here. Please see paper copy Formula (I) to processes for preparing such compounds, to their utility as P2Y 12 inhibitors and as anti-thrombotic agents etc, their use as medicaments in cardiovascular diseases as well as pharmaceutical compositions containing them.

  本发明涉及某些新的Formula (I)式吡啶类似物，化学式应在此处插入。请参见纸质副本Formula (I)，以及制备这些化合物的过程，它们作为P2Y12抑制剂和抗血栓剂等的效用，它们在心血管疾病中作为药物的用途以及含有它们的制药组合物。