5-(2-chlorophenyl)-1-(2,6-dichlorophenyl)-7-(piperidin-4-ylamino)-3,4-dihydroquinazolin-2(1H)-one | 444661-91-0

• 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: 5-(2-chlorophenyl)-1-(2,6-dichlorophenyl)-7-(piperidin-4-ylamino)-3,4-dihydroquinazolin-2(1H)-one
• 英文别名: 5-(2-chlorophenyl)-1-(2,6-dichlorophenyl)-7-(piperidin-4-ylamino)-3,4-dihydroquinazolin-2-one
• CAS: 444661-91-0
• 化学式: C₂₅H₂₃Cl₃N₄O
• 分子量: 501.843
• InChiKey: KYTWYELKTBDZFP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.9
• 重原子数：
  33
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  56.4
• 氢给体数：
  3
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  丙酮 、 5-(2-chlorophenyl)-1-(2,6-dichlorophenyl)-7-(piperidin-4-ylamino)-3,4-dihydroquinazolin-2(1H)-one 在 sodium cyanoborohydride 作用下， 以 甲醇 为溶剂， 生成 5-(2-Chlorophenyl)-1-(2,6-dichlorophenyl)-7-[(1-propan-2-ylpiperidin-4-yl)amino]-3,4-dihydroquinazolin-2-one
  参考文献：
  名称：

  p38 Inhibitors: piperidine- and 4-aminopiperidine-substituted naphthyridinones, quinolinones, and dihydroquinazolinones

  摘要：

  We have synthesized a series of C7-piperidine- and 4-aminopiperidine-substituted naphthyridinones, quinolinones, and dihydroquinazolinones that are highly potent inhibitors of both p38 MAP kinase activity and TNF-alpha release. The 4-aminopenta-methylpiperidine naphthyridinone 5, which was designed to block metabolism at major 'hot spots', combined excellent inhibitory potency with good oral bioavailability in the rat. (C) 2002 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(02)00990-3
• 作为产物：
  描述：

  1-bromomethyl-2,6-dibromo-4-nitrobenzene 在 palladium on activated charcoal copper(l) iodide 、 四(三苯基膦)钯 、 氢气 、 三乙酰氧基硼氢化钠 、 sodium carbonate 、 potassium carbonate 、 溶剂黄146 、 N,N-二异丙基乙胺 、 三氟乙酸 作用下， 以 乙醇 、 二氯甲烷 、 乙酸乙酯 、 1,2-二氯乙烷 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 生成 5-(2-chlorophenyl)-1-(2,6-dichlorophenyl)-7-(piperidin-4-ylamino)-3,4-dihydroquinazolin-2(1H)-one
  参考文献：
  名称：

  p38 Inhibitors: piperidine- and 4-aminopiperidine-substituted naphthyridinones, quinolinones, and dihydroquinazolinones

  摘要：

  We have synthesized a series of C7-piperidine- and 4-aminopiperidine-substituted naphthyridinones, quinolinones, and dihydroquinazolinones that are highly potent inhibitors of both p38 MAP kinase activity and TNF-alpha release. The 4-aminopenta-methylpiperidine naphthyridinone 5, which was designed to block metabolism at major 'hot spots', combined excellent inhibitory potency with good oral bioavailability in the rat. (C) 2002 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(02)00990-3

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。
• Design and synthesis of potent, orally bioavailable dihydroquinazolinone inhibitors of p38 MAP kinase
  作者：John E. Stelmach、Luping Liu、Sangita B. Patel、James V. Pivnichny、Giovanna Scapin、Suresh Singh、Cornelis E.C.A. Hop、Zhen Wang、John R. Strauss、Patricia M. Cameron、Elizabeth A. Nichols、Stephen J. O'Keefe、Edward A. O'Neill、Dennis M. Schmatz、Cheryl D. Schwartz、Chris M. Thompson、Dennis M. Zaller、James B. Doherty

  DOI：10.1016/s0960-894x(02)00752-7

  日期：2003.1

  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.
• 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