8-溴-4-(4-甲基哌嗪-1-基)喹唑啉-2-胺 | 1258630-98-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 中文名称: 8-溴-4-(4-甲基哌嗪-1-基)喹唑啉-2-胺
• 英文名称: 8-bromo-4-(4-methylpiperazin-1-yl)quinazolin-2-amine
• CAS: 1258630-98-6
• 化学式: C₁₃H₁₆BrN₅
• 分子量: 322.208
• InChiKey: ZADMGAMTQIMWQB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  19
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  58.3
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  3-呋喃硼酸 、 8-溴-4-(4-甲基哌嗪-1-基)喹唑啉-2-胺 在 四(三苯基膦)钯 、 sodium carbonate 作用下， 以 乙醇 、 甲苯 为溶剂， 反应 1.0h， 以43%的产率得到8-(furan-3-yl)-4-(4-methylpiperazin-1-yl)quinazolin-2-amine
  参考文献：
  名称：

  Ligand based design of novel histamine H4 receptor antagonists; fragment optimization and analysis of binding kinetics

  摘要：

  The histamine H-4 receptor is a G protein-coupled receptor that has attracted much interest for its role in inflammatory and immunomodulatory functions. In our search for new H4R ligands, a low affinity isoquinoline fragment was optimized to 7-(furan-2-yl)-4-(piperazin-1-yl)quinazolin-2-amine (VUF11489), as a new H4R antagonist. Analysis of its binding kinetics at the human H4R showed this compound to have a very different dissociative half-life in comparison with reference antagonist JNJ7777120. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.10.104
• 作为产物：
  描述：

  2-氨基-8-溴喹唑啉-4(3H)-酮 在 N,N-二异丙基乙胺 、 三氯氧磷 作用下， 以 1,4-二氧六环 、 乙腈 为溶剂， 反应 17.75h， 生成 8-溴-4-(4-甲基哌嗪-1-基)喹唑啉-2-胺
  参考文献：
  名称：

  Ligand based design of novel histamine H4 receptor antagonists; fragment optimization and analysis of binding kinetics

  摘要：

  The histamine H-4 receptor is a G protein-coupled receptor that has attracted much interest for its role in inflammatory and immunomodulatory functions. In our search for new H4R ligands, a low affinity isoquinoline fragment was optimized to 7-(furan-2-yl)-4-(piperazin-1-yl)quinazolin-2-amine (VUF11489), as a new H4R antagonist. Analysis of its binding kinetics at the human H4R showed this compound to have a very different dissociative half-life in comparison with reference antagonist JNJ7777120. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.10.104

文献信息

• [EN] QUINAZOLINE DERIVATIVES AS HISTAMINE H4-RECEPT0R INHIBITORS FOR USE IN THE TREATMENT OF INFLAMMATORY DISORDERS<br/>[FR] DÉRIVÉS DE LA QUINAZOLINE SERVANT D'INHIBITEURS DU RÉCEPTEUR H4 DE L'HISTAMINE DESTINÉS À ÊTRE UTILISÉS DANS LE TRAITEMENT DE TROUBLES INFLAMMATOIRES
  申请人：VERENIGING VOOR CHRISTELIJK HOGER ONDERWIJS WETENSCHAPPELIJK ONDERZOEK EN PATIENTENZORG

  公开号：WO2010146173A1

  公开（公告）日：2010-12-23

  Compounds that modulate the histamine H4 receptor, and which may be useful for treating or preventing disorders and conditions mediated by the histamine H4 receptor, e.g. inflammation, are of Formula (I):

  调节组胺H4受体的化合物，可能用于治疗或预防由组胺H4受体介导的疾病和症状，例如炎症，其化学式为(I)：
• Quinazoline derivatives as histamine H4-receptor inhibitors for use in the treatment of inflammatory disorders
  申请人：Vereniging voor Christelijk Hoger Onderwijs, Wetenschappelijk Onderzoek en Patiëntenzorg

  公开号：EP2270002A1

  公开（公告）日：2011-01-05

  Compounds that modulate the histamine H4 receptor, and which may be useful for treating or preventing disorders and conditions mediated by the histamine H4 receptor, e.g. inflammation, are of formula (I) Wherein R2 is H or NRxRy, where Rx and Ry are each independently selected from H, C1-6 alkyl and (CH2)1-3C3-7cycloalkyl; or Rx and Ry, together with the nitrogen atom to which they are bound form a 4, 5 or 6 membered heterocyclic group; NR'R" is one of the following moieties, wherein R' and R" are taken together or separately as defined by each of one said moieties: q is 0 or 1; p is 0 or 1; r is 0 or 1; s is 0 or 1; Ra is H or OH or F; Rb and Rc are each independently H or C1-3 alkyl; Rd is H or OH or NH2; Re and Rf are each methyl, or Re and Rf taken together form a methylene or ethylene bridge; and R7 and R8 are independently selected form H, F, Cl, Br, I, C1-4 alkyl, C2-5 alkenyl, C2-5 alkynyl, C1-4 alkoxy, C1-4 alkylthio, (CH2)0-3C3-7cycloalkyl, O-C3-6 cycloalkyl, phenyl, benzyl, O-phenyl, NH-phenyl, S-phenyl, O-C1-4 alkyl-phenyl, C1-4 alkyl-phenyl, CF3, O-CF3, S-CF3, hydroxy, nitro, cyano, O-C1-4 alkyl-N(CH3)2, and NRmRn, wherein Rm and Rn are independently selected from H, C1-4 alkyl, phenyl, benzyl and phenethyl, and wherein any phenyl, alkyl or cycloalkyl moiety is optionally substituted with 1 to 3 substituents selected from C1-3 alkyl, halogen, hydroxy, amino and C1-3 alkoxy; or pharmaceutically acceptable salt, ester, or solvate thereof.

  可调节组胺 H4 受体并可用于治疗或预防由组胺 H4 受体介导的疾病和病症（如炎症）的化合物如式 (I) 所示 其中 R2是H或NRxRy，其中Rx和Ry各自独立地选自H、C1-6烷基和(CH2)1-3C3-7环烷基；或Rx和Ry与它们结合的氮原子一起形成4、5或6个成员的杂环基团； NR'R" 是下列分子之一，其中 R' 和 R" 可按上述各分子的定义一起或分开使用： q 为 0 或 1 p 为 0 或 1 R 为 0 或 1 s 为 0 或 1； Ra 是 H 或 OH 或 F； Rb 和 Rc 各自独立地为 H 或 C1-3 烷基； Rd 是 H 或 OH 或 NH2； Re 和 Rf 各自是甲基，或 Re 和 Rf 共同形成亚甲基或亚乙基桥；以及 R7 和 R8 独立地选形成 H、F、Cl、Br、I、C1-4 烷基、C2-5 烯基、C2-5 炔基、C1-4 烷氧基、C1-4 烷硫基、(CH2)0-3C3-7 环烷基、O-C3-6 环烷基、苯基、苄基、O-苯基、NH-苯基、S-苯基、O-C1-4 烷基-苯基、C1-4 烷基-苯基、CF3、O-CF3、S-CF3、羟基、硝基、氰基、O-C1-4-烷基-N(CH3)2，和 NRmRn，其中 Rm 和 Rn 独立选自 H、C1-4-烷基、苯基、苄基和苯乙基，任何苯基、烷基或环烷基可任选被 1 至 3 个选自 C1-3 烷基、卤素、羟基、氨基和 C1-3 烷氧基的取代基取代； 或其药学上可接受的盐、酯或溶液。
• H4 RECEPTOR INHIBITORS FOR TREATING TINNITUS
  申请人：Sensorion

  公开号：EP2858647A1

  公开（公告）日：2015-04-15
• US9688989B2
  申请人：——

  公开号：US9688989B2

  公开（公告）日：2017-06-27
• [EN] H4 RECEPTOR INHIBITORS FOR TREATING TINNITUS<br/>[FR] INHIBITEURS DES RÉCEPTEURS H4 POUR LE TRAITEMENT DES ACOUPHÈNES
  申请人：SENSORION

  公开号：WO2013182711A1

  公开（公告）日：2013-12-12

  The invention relates to Histamine type 4 receptor (H4R) inhibitors for treating tinnitus.