methyl 5-bromo-1-(2,6-dichlorophenyl)-3-(4-methoxybenzyl)-2-oxo-1,2,3,4-tetrahydroquinazoline-7-carboxylate | 444663-84-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: methyl 5-bromo-1-(2,6-dichlorophenyl)-3-(4-methoxybenzyl)-2-oxo-1,2,3,4-tetrahydroquinazoline-7-carboxylate
• 英文别名: methyl 5-bromo-1-(2,6-dichlorophenyl)-3-[(4-methoxyphenyl)methyl]-2-oxo-4H-quinazoline-7-carboxylate
• CAS: 444663-84-7
• 化学式: C₂₄H₁₉BrCl₂N₂O₄
• 分子量: 550.236
• InChiKey: FHIQBCDOBKEJSJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.7
• 重原子数：
  33
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  59.1
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  methyl 5-bromo-1-(2,6-dichlorophenyl)-3-(4-methoxybenzyl)-2-oxo-1,2,3,4-tetrahydroquinazoline-7-carboxylate 在 三氟乙酸 作用下， 生成 Methyl 5-bromo-1-(2,6-dichlorophenyl)-2-oxo-3,4-dihydroquinazoline-7-carboxylate
  参考文献：
  名称：

  Design and synthesis of potent, orally bioavailable dihydroquinazolinone inhibitors of p38 MAP kinase

  摘要：

  The development of potent, orally bioavailable (in rat) and selective dihydroquinazolinone inhibitors of p38alpha MAP kinase is described. These analogues are hybrids of a pyridinylimidazole p38alpha inhibitor reported by Merck Research Laboratories and VX-745. Optimization of the C-5 phenyl and the C-7 piperidinyl substituents led to the identification of 15i which gave excellent suppression of TNF-alpha production in LPS-stimulated whole blood (IC50 = 10 nM) and good oral exposure in rats (F = 68%, AUCn PO = 0.58 muM h). (C) 2002 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(02)00752-7
• 作为产物：
  描述：

  3,5-二溴-4-甲基苯甲酸甲酯 在 N-溴代丁二酰亚胺(NBS) 、 copper(l) iodide 、 potassium carbonate 、 过氧化苯甲酰 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 0.25h， 生成 methyl 5-bromo-1-(2,6-dichlorophenyl)-3-(4-methoxybenzyl)-2-oxo-1,2,3,4-tetrahydroquinazoline-7-carboxylate
  参考文献：
  名称：

  Design and synthesis of potent, orally bioavailable dihydroquinazolinone inhibitors of p38 MAP kinase

  摘要：

  The development of potent, orally bioavailable (in rat) and selective dihydroquinazolinone inhibitors of p38alpha MAP kinase is described. These analogues are hybrids of a pyridinylimidazole p38alpha inhibitor reported by Merck Research Laboratories and VX-745. Optimization of the C-5 phenyl and the C-7 piperidinyl substituents led to the identification of 15i which gave excellent suppression of TNF-alpha production in LPS-stimulated whole blood (IC50 = 10 nM) and good oral exposure in rats (F = 68%, AUCn PO = 0.58 muM h). (C) 2002 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(02)00752-7

文献信息

• (Halo-benzo carbonyl)heterocyclo fused phenyl p38 kinase inhibiting agents
  申请人：——

  公开号：US20030092712A1

  公开（公告）日：2003-05-15

  Compounds described by the chemical formula (I) or a pharmaceutically acceptable salt thereof: 1 are inhibitors of p38 useful in the treatment of inflammatory diseases such as arthritis.

  根据化学公式(I)或其药物可接受的盐描述的化合物： 1 是p38的抑制剂，可用于治疗类风湿性关节炎等炎症性疾病。
• [EN] (HALO-BENZO CARBONYL)HETEROCYCLO FUSED PHENYL P38 KINASE INHIBITING AGENTS<br/>[FR] AGENTS INHIBITEURS DE P38 KINASE (HALO-BENZO CARBONYL)HETEROCYCLO- FUSIONNES PHENYL
  申请人：MERCK & CO INC

  公开号：WO2002058695A1

  公开（公告）日：2002-08-01

  Compounds described by the chemical formula (I) or a pharmaceutically acceptable salt thereof, are inhibitors of p38 useful in the treatment of inflammatory diseases such as arthritis.

  化学式（I）或其药学上可接受的盐所描述的化合物是p38的抑制剂，可用于治疗炎症性疾病，如关节炎。
• EP1345603A4
  申请人：——

  公开号：EP1345603A4

  公开（公告）日：2004-09-08
• (HALO-BENZO CARBONYL)HETEROCYCLO FUSED PHENYL P38 KINASE INHIBITING AGENTS
  申请人：Merck & Co., Inc.

  公开号：EP1345603A1

  公开（公告）日：2003-09-24
• US6809199B2
  申请人：——

  公开号：US6809199B2

  公开（公告）日：2004-10-26