2-chloro-5-(3,5-dioxo-4,5-dihydro-3H-[1,2,4]triazin-2-yl)-benzoyl chloride | 531507-38-7

• 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)-benzoyl chloride
• 英文别名: 2-chloro-5-(3,5-dioxo-1,2,4-triazin-2-yl)benzoyl chloride
• CAS: 531507-38-7
• 化学式: C₁₀H₅Cl₂N₃O₃
• 分子量: 286.074
• InChiKey: OPGPMMKHORXZDT-UHFFFAOYSA-N

物化性质

• 密度：
  1.70±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 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：
  78.8
• 氢给体数：
  1
• 氢受体数：
  4

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)-benzoyl chloride 在 caesium carbonate 、 sodium hydroxide 作用下， 以 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 、 草酰氯 、 溶剂黄146 、 巯基乙酸 、 sodium hydroxide 、 sodium nitrite 作用下， 以 二氯甲烷 、 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)-benzoyl chloride
  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。
• 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
• METHOD FOR PREPARING 5-¬4-(2-HYDROXY-ETHYL)-3,5-DIOXO-4,5-DIHYDRO-3H-¬1,2,4|-TRIAZIN-2-YL|BENZAMIDE DERIVATIVES WITH P2X7 INHIBITING ACTIVITY BY REACTION OF THE DERIVATIVE UNSUBSTITUTED IN 4-POSITION OF THE TRIAZINE WITH AN OXIRAN IN THE PRESENCE OF A LEWIS ACID
  申请人：Pfizer Products Incorporated

  公开号：EP1768965A1

  公开（公告）日：2007-04-04
• METHOD FOR PREPARING 5-[4-(2-HYDROXY-PROPYL)-3,5-DIOXO-4,5-DIHYDRO-3H[1,2,4]TRIAZIN-2-YL]-BENZAMIDE DERIVATIVES BY DEPROTECTING THE HYDROXYL-PROTECTED PRECURSERS
  申请人：Pfizer Products Inc.

  公开号：EP1776352A1

  公开（公告）日：2007-04-25