2-chloro-5-(3,5-dioxo-4,5-dihydro-3H-[1,2,4]triazin-2-yl)-benzoic acid | 524712-41-2

• 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-chloro-5-(3,5-dioxo-4,5-dihydro-3H-[1,2,4]triazin-2-yl)-benzoic acid
• 英文别名: 2-Chloro-5-(3,5-dioxo-4,5-dihydro-1,2,4-triazin-2(3H)-YL)benzoic acid；2-chloro-5-(3,5-dioxo-1,2,4-triazin-2-yl)benzoic acid
• CAS: 524712-41-2
• 化学式: C₁₀H₆ClN₃O₄
• 分子量: 267.628
• InChiKey: PLVVNHOUDKRXOX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  99.1
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-chloro-5-(3,5-dioxo-4,5-dihydro-3H-[1,2,4]triazin-2-yl)-benzoic acid 在 草酰氯 、 caesium carbonate 、 sodium hydroxide 作用下， 以 二氯甲烷 、 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：

  5-氨基-2-氯苯甲酸 在 盐酸 、 溶剂黄146 、 巯基乙酸 、 sodium hydroxide 、 sodium nitrite 作用下， 以 水 为溶剂， 反应 1.83h， 生成 2-chloro-5-(3,5-dioxo-4,5-dihydro-3H-[1,2,4]triazin-2-yl)-benzoic 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。
• Methods for preparing P2X7 inhibitors
  申请人：Li Bryan Zhengong

  公开号：US20050288256A1

  公开（公告）日：2005-12-29

  The present invention relates to the methods for preparing compounds of the formula I: or the pharmaceutically acceptable salts thereof, wherein R 1 , R 2 , R 4 , R 10 , and R 11 have any of the values defined in the specification. The compounds of the present invention are useful in the treatment of diseases, including inflammatory diseases such as rheumatoid arthritis.

  本发明涉及制备以下化合物的方法：或其在药学上可接受的盐，其中R1、R2、R4、R10和R11具有规范中定义的任一值。本发明的化合物在治疗疾病方面具有用途，包括类风湿性关节炎等炎症性疾病。
• 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