VUF 10505 | 1001065-76-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: VUF 10505
• 英文别名: 6-chloro-N-(4-methoxybenzyl)-2-(4-methylpiperazin-1-yl)-quinazolin-4-amine；6-chloro-N-[(4-methoxyphenyl)methyl]-2-(4-methylpiperazin-1-yl)quinazolin-4-amine
• CAS: 1001065-76-4
• 化学式: C₂₁H₂₄ClN₅O
• 分子量: 397.907
• InChiKey: WLKCSPVGPMCSMZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  28
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  53.5
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  N-甲基哌嗪 、 C₁₆H₁₃Cl₂N₃O 以 乙酸乙酯 为溶剂， 反应 0.17h， 以202 mg的产率得到VUF 10505
  参考文献：
  名称：

  Discovery of Quinazolines as Histamine H₄ Receptor Inverse Agonists Using a Scaffold Hopping Approach

  摘要：

  From a series of small fragments that was designed to probe the histamine H-4 receptor (H4R), we previously described quinoxaline-containing fragments that were grown into high affinity H4R ligands in a process that was guided by pharmacophore modeling. With a scaffold hopping exercise and using the same in silico models, we now report the identification and optimization of a series of quinazoline-containing H4R compounds. This approach led to the discovery of 6-chloi-o-N-(furan-3-yl)methyl)2-(4-methylpiperzin-1-yl)quinazolin-4-amine (VUF10499, 54) and 6-chloro-2-(4-methylpiperazin-1-yl)-N-(thiophen-2-ylmethyl)quinazolin-4-amine (VUF10497, 55) as potent human H4R inverse agonists (pK(i) = 8.12 and 7.57, respectively). Interestingly, both compounds also possess considerable affinity for the human histamine Hi receptor (H1R) and therefore represent a novel class of dual action H1R/H4R ligands, a profile that potentially leads to added therapeutic benefit. Compounds from this novel series of quirlazolines are antagonists at the rat H4R and were found to possess anti-inflammatory properties in vivo in the rat.

  DOI：

  10.1021/jm800876b

文献信息

• RAF INHIBITOR COMPOUNDS AND METHODS OF USE THEREOF
  申请人：Buckmelter Alexandre J.

  公开号：US20100063066A1

  公开（公告）日：2010-03-11

  Compounds of Formulas (I), (IIA) and (IIIA) are useful for inhibiting Raf kinase and for treating disorders mediated thereby. Methods of using compounds of Formulas (I), (IIA) and (IIIA) and stereoisomers and pharmaceutically acceptable salts thereof, for in vitro, in situ, and in vivo diagnosis, prevention or treatment of such disorders in mammalian cells, or associated pathological conditions are disclosed.

  化合物(I)、(IIA)和(IIIA)的配方对抑制Raf激酶和治疗由此介导的疾病很有用。公开了使用化合物(I)、(IIA)和(IIIA)及其立体异构体和药用盐，在哺乳动物细胞中进行体外、体内和体内诊断、预防或治疗这些疾病或相关病理状况的方法。
• Quinazolines and Related Heterocyclic Compounds, and Their Therapeutic Use
  申请人：Smits Rogier Adriaan

  公开号：US20100016293A1

  公开（公告）日：2010-01-21

  Compounds that interact with 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 Q is CR 1 or N; X is CR 2 or N, provided that Q and X are not both N; Y is CR 3 or N; Z is CH or N; R 1 , R 2 , R 3 , R 4 , R 5 and R 6 are independently H, F, Cl, Br, I, or a hydrocarbon group which optionally contains one or more heteroatoms; and R7 is a heterocyclic radical including one or more N atoms; or a pharmaceutically acceptable salt, ester or solvate thereof.

  与组织胺H4受体相互作用的化合物，可能用于治疗或预防由组织胺H4受体介导的疾病和症状，如炎症，其化学式为(I)，其中Q为CR1或N；X为CR2或N，前提是Q和X不同时为N；Y为CR3或N；Z为CH或N；R1、R2、R3、R4、R5和R6独立地为H、F、Cl、Br、I或可选择含有一个或多个杂原子的碳氢基团；R7为包含一个或多个N原子的杂环基团；或其药用盐、酯或溶剂化合物。
• FUSED BICYCLIC COMPOUNDS INTERACTING WITH THE HISTAMINE H4 RECEPTOR
  申请人：Vereniging voor Christelijk Hoger Onderwijs, Wetenschappelijk Onderzoek en Patiëntenzorg

  公开号：EP2044027A2

  公开（公告）日：2009-04-08
• [EN] RAF INHIBITOR COMPOUNDS AND METHODS OF USE THEREOF<br/>[FR] COMPOSÉS INHIBITEURS DE LA KINASE RAF ET PROCÉDÉS D'UTILISATION DE CEUX-CI
  申请人：ARRAY BIOPHARMA INC

  公开号：WO2008028141A2

  公开（公告）日：2008-03-06

  [EN] Compounds of Formulas (I), (IIA) and (IIIA) are useful for inhibiting Raf kinase and for treating disorders mediated thereby. Methods of using compounds of Formulas (I), (IIA) and (IIIA) and stereoisomers and pharmaceutically acceptable salts thereof, for in vitro, in situ, and in vivo diagnosis, prevention or treatment of such disorders in mammalian cells, or associated pathological conditions are disclosed.
  [FR] L'invention concerne des composés de formules (I), (IIA) et (IIIA) à utiliser pour inhiber la kinase Raf et pour traiter des états dont la médiation est assurée par ladite kinase. L'invention concerne également des procédés d'utilisation desdits composés de formules (I), (IIA) et (IIIA), de stéréoisomères et de sels acceptables sur le plan pharmaceutique de ceux-ci, pour le diagnostic, la prévention ou le traitement in vitro, in situ, et in vivo desdits états dans des cellules mammifère, ou d'états pathologique associés.
• [EN] QUINAZOLINES AND RELATED HETEROCYCLIC COMPOUNDS, AND THEIR THERAPEUTIC USE<br/>[FR] QUINAZOLINES ET COMPOSÉS HÉTÉROCYCLIQUES ASSOCIÉS, ET LEUR UTILISATION DANS LE DOMAINE THÉRAPEUTIQUE
  申请人：VERENIGING VOOR CHRISTELIJK HOGER ONDERWIJS WETENSCHAPPELIJK ONDERZOEK EN PATIENTENZORG

  公开号：WO2008003702A2

  公开（公告）日：2008-01-10

  [EN] Compounds that interact with 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 Q is CR¹ or N; X is CR² or N, provided that Q and X are not both N; Y is CR³ or N; Z is CH or N; R¹, R², R³, R⁴, R⁵ and R⁶ are independently H, F, Cl, Br, I, or a hydrocarbon group which optionally contains one or more heteroatoms; and R7 is a heterocyclic radical including one or more N atoms; or a pharmaceutically acceptable salt, ester or solvate thereof.
  [FR] L'invention concerne des composés qui interagissent avec le récepteur d'histamine H4 et peuvent être utiles pour le traitement ou la prévention de troubles et d'états induits par le récepteur de l'histamine H4, p. ex. l'inflammation. Les composés selon l'invention sont représentés par la formule (I) dans laquelle Q représente CR¹ ou N ; X représente CR² ou N, à condition que Q et X ne représentent pas tous les deux N ; Y représente CR³ ou N ; Z représente CH ou N ; R¹, R², R³, R⁴, R⁵ et R⁶ sont indépendamment H, F, Cl, Br, I ou un groupement hydrocarboné contenant éventuellement un ou plusieurs hétéroatomes ; et R7 représente un radical hétérocyclique comprenant un ou plusieurs atomes N ; ou un de leurs sels, esters ou solvates pharmaceutiquement acceptables.