6-chloro-2-(4-methylpiperazin-1-yl)quinazolin-4(3H)-one | 33017-92-4

• 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: 6-chloro-2-(4-methylpiperazin-1-yl)quinazolin-4(3H)-one
• 英文别名: VUF10331；6-chloro-2-(4-methyl-piperazin-1-yl)-3H-quinazolin-4-one；4(3H)-Quinazolinone, 6-chloro-2-(4-methyl-1-piperazinyl)-；6-chloro-2-(4-methylpiperazin-1-yl)-3H-quinazolin-4-one
• CAS: 33017-92-4
• 化学式: C₁₃H₁₅ClN₄O
• 分子量: 278.741
• InChiKey: BNASSGFQLMOZKG-UHFFFAOYSA-N

物化性质

• 熔点：
  >250 °C
• 沸点：
  435.5±55.0 °C(Predicted)
• 密度：
  1.44±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 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：
  47.9
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  6-氯喹唑啉-2,4-二酮 在 sodium hydroxide 、 N,N-二甲基苯胺 、 三氯氧磷 作用下， 以 乙醇 、 水 为溶剂， 反应 8.0h， 生成 6-chloro-2-(4-methylpiperazin-1-yl)quinazolin-4(3H)-one
  参考文献：
  名称：

  Synthesis and antihyperglycemic activity of suitably functionalized 3H-quinazolin-4-ones☆

  摘要：

  A series of 2-sec-amino-3H-quinazolin-4-ones (4a-p) and 4-sec-amino-2-chloroquinazolines (5a-b) have been synthesized by nucleophilic substitution reaction of 2-chloro-4(3H)-quinazolones (3) and 2,4-dichloroquinazolines (2) with amines, respectively. Most of the synthesized compounds were evaluated for antihyperglycemic activity but only 4a,b,d,j,o displayed significant reduction in blood glucose level in streptozotocin and sucrose loaded rat models. (C) 2003 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(03)00142-1

文献信息

• Efficient Copper-Catalyzed Synthesis of 2-Amino-4(<i>3H</i>)-quinazolinone and 2-Aminoquinazoline Derivatives
  作者：Hua Fu、Renzhong Qiao、Xuhu Huang、Haijun Yang、Yufen Zhao

  DOI：10.1055/s-0029-1216871

  日期：——

  We have developed a versatile and efficient method for copper-catalyzed synthesis of both 2-amino-4(3H)-quinazolinone and 2-aminoquinazoline derivatives. The protocol uses readily available substituted 2-halobenzoic acids, 2-bromobenzaldehyde, 2-bromophenyl ketones and guanidines as the starting materials, inexpensive copper(I) iodide as the catalyst, and the method has important application values

  我们已经开发了一种通用且有效的方法，用于铜催化的2-氨基-4（3H）-喹唑啉酮和2-氨基喹唑啉衍生物的合成。该方案使用容易获得的取代的2-卤代苯甲酸，2-溴苯甲醛，2-溴苯基酮和胍作为起始原料，廉价的碘化亚铜（I）作为催化剂，该方法对于在N-杂环结构中的应用具有重要的应用价值。有机化学和药物化学。 铜催化-交叉偶联-2-氨基-4（3H）-喹唑啉酮-2-氨基喹唑啉-合成方法
• 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。
• Discovery of Quinazolines as Histamine H₄ Receptor Inverse Agonists Using a Scaffold Hopping Approach
  作者：Rogier A. Smits、Iwan J. P. de Esch、Obbe P. Zuiderveld、Joachim Broeker、Kamonchanok Sansuk、Elena Guaita、Gabriella Coruzzi、Maristella Adami、Eric Haaksma、Rob Leurs

  DOI：10.1021/jm800876b

  日期：2008.12.25

  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.
• [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.