2-(3-Carboxy-4-chlorophenyl)-3,5-dioxo-2,3,4,5-tetrahydro-1,2,4-triazine-6-carboxylic acid | 524712-40-1

• 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: 2-(3-Carboxy-4-chlorophenyl)-3,5-dioxo-2,3,4,5-tetrahydro-1,2,4-triazine-6-carboxylic acid
• 英文别名: 2-(3-carboxy-4-chlorophenyl)-3,5-dioxo-1,2,4-triazine-6-carboxylic acid
• CAS: 524712-40-1
• 化学式: C₁₁H₆ClN₃O₆
• 分子量: 311.638
• InChiKey: BVWRHIRDAMQBNF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  21
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  136
• 氢给体数：
  3
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  2-(3-Carboxy-4-chlorophenyl)-3,5-dioxo-2,3,4,5-tetrahydro-1,2,4-triazine-6-carboxylic acid 在 草酰氯 、 caesium carbonate 、 巯基乙酸 、 sodium hydroxide 作用下， 以 二氯甲烷 、 水 、 丙酮 为溶剂， 生成 2-chloro-N-((1-hydroxycycloheptyl)methyl)-5-(4-methyl-3,5-dioxo-4,5-dihydro-1,2,4-triazin-2(3H)-yl)benzamide
  参考文献：
  名称：

  Optimization of the physicochemical and pharmacokinetic attributes in a 6-azauracil series of P2X7 receptor antagonists leading to the discovery of the clinical candidate CE-224,535

  摘要：

  High throughput screening (HTS) of our compound file provided an attractive lead compound with modest P2X(7) receptor antagonist potency and high selectivity against a panel of receptors and channels, but also with high human plasma protein binding and a predicted short half-life in humans. Multi-parameter optimization was used to address the potency, physicochemical and pharmacokinetic properties which led to potent P2X(7)R antagonists with good disposition properties. Compound 33 (CE-224,535) was advanced to clinical studies for the treatment of rheumatoid arthritis. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.04.077
• 作为产物：
  描述：

  (1,3-二氧代丙烷-1,3-二基)双氨基甲酸二乙酯 、 5-氨基-2-氯苯甲酸 在 盐酸 、 溶剂黄146 、 sodium nitrite 、 sodium acetate 作用下， 反应 1.83h， 以46%的产率得到2-(3-Carboxy-4-chlorophenyl)-3,5-dioxo-2,3,4,5-tetrahydro-1,2,4-triazine-6-carboxylic acid
  参考文献：
  名称：

  Optimization of the physicochemical and pharmacokinetic attributes in a 6-azauracil series of P2X7 receptor antagonists leading to the discovery of the clinical candidate CE-224,535

  摘要：

  High throughput screening (HTS) of our compound file provided an attractive lead compound with modest P2X(7) receptor antagonist potency and high selectivity against a panel of receptors and channels, but also with high human plasma protein binding and a predicted short half-life in humans. Multi-parameter optimization was used to address the potency, physicochemical and pharmacokinetic properties which led to potent P2X(7)R antagonists with good disposition properties. Compound 33 (CE-224,535) was advanced to clinical studies for the treatment of rheumatoid arthritis. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.04.077

文献信息

• Benzamide, heteroarylamide and reverse amides
  申请人：Pfizer Inc.

  公开号：US20030186981A1

  公开（公告）日：2003-10-02

  The present invention relates to novel to P2X 7 inhibitors of formula I 1 and to processes for their preparation, intermediates useful in their preparation, pharmaceutical compositions containing them, and their use in therapy. The active compounds of the present invention are potent inhibitors of P2X 7 and as such are useful in the treatment of inflammation, osteoarthritis, rheumatoid arthritis, cancer, reperfusion or ischemia in stroke or heart attack, autoimmune diseases and other disorders.

  本发明涉及一种新的P2X7抑制剂的I1式，以及其制备方法、制备中间体、含有它们的药物组合物，以及它们在治疗中的应用。本发明的活性化合物是P2X7的有效抑制剂，因此在治疗炎症、骨关节炎、类风湿关节炎、癌症、中风或心脏病发作中的再灌注或缺血、自身免疫疾病和其他疾病中具有用途。
• N-alkyl-adamantyl triazinyl benzamide derivatives
  申请人：Pfizer Inc.

  公开号：US20030144293A1

  公开（公告）日：2003-07-31

  The present invention relates to novel to N-alkyl adamantyl triazinyl benzylamide derivatives of formmula I 1 and to processs for their preparation, intermediates useful in their preparation, pharmaceutical compositions containing them, and their use in therapy. The active compounds of the present invention are useful in the treatment of inflammation, osteoarthritis, rhematoid arthritis, cancer, reperfusion or ischemia in stroke or heart attack, autoimmune diseases and other disorders.

  本发明涉及一种新型的N-烷基金刚烷三嗪基苯甲酰胺衍生物（I1式），以及它们的制备方法、在制备中有用的中间体、含有它们的药物组合物，以及它们在治疗中的应用。本发明的活性化合物在治疗炎症、骨关节炎、类风湿性关节炎、癌症、中风或心脏病的再灌注或缺血、自身免疫性疾病和其他疾病中有用。
• N-adamantylalkyl benzamide derivates as p2x7-receptor antagonists
  申请人：Pfizer Products Inc.

  公开号：EP1310493A1

  公开（公告）日：2003-05-14

  The present invention relates to novel to N-adamantylalkyl benzylamide derivatives of formmula I and to process for their preparation, intermediates useful in their preparation, pharmaceutical compositions containing them, and their use in the treatment of inflammation, osteoarthritis, rheumatoid arthritis, cancer, reperfusion or ischemia in stroke or heart attack, autoimmune diseases and other disorders.

  本发明涉及形式 I 的新型 N-金刚烷基苄酰胺衍生物 及其制备工艺、用于制备它们的中间体、含有它们的药物组合物，以及它们在治疗炎症、骨关节炎、类风湿性关节炎、癌症、中风或心脏病发作中的再灌注或缺血、自身免疫性疾病和其他疾病中的用途。
• BENZAMIDE AND HETEROARYLAMIDE AS P2X7 RECEPTOR ANTAGONISTS
  申请人：Pfizer Products Inc.

  公开号：EP1448535A1

  公开（公告）日：2004-08-25
• US6927219B2
  申请人：——

  公开号：US6927219B2

  公开（公告）日：2005-08-09