(E)-2-(prop-1-en-1-yl)quinazolin-4(3H)-one | 127033-49-2

• 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: (E)-2-(prop-1-en-1-yl)quinazolin-4(3H)-one
• 英文别名: ((E)-2-Propenyl)-3H-quinazolin-4-one；2-[(E)-prop-1-enyl]-3H-quinazolin-4-one
• CAS: 127033-49-2
• 化学式: C₁₁H₁₀N₂O
• 分子量: 186.213
• InChiKey: CAKJWBJMCIKHHV-GORDUTHDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  14
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  41.5
• 氢给体数：
  1
• 氢受体数：
  1

反应信息

• 作为产物：
  描述：

  (E)-But-2-enoic acid (2-cyano-phenyl)-amide 在 sodium hydroxide 、 双氧水 作用下， 以 乙醇 为溶剂， 反应 1.0h， 生成 (E)-2-(prop-1-en-1-yl)quinazolin-4(3H)-one
  参考文献：
  名称：

  Synthesis and biological evaluation of 2-styrylquinazolin-4(3H)-ones, a new class of antimitotic anticancer agents which inhibit tubulin polymerization

  摘要：

  A novel series of 2-styrylquinazolin-4(3H-ones which inhibited tubulin polymerization and the growth of L1210 murine leukemia cells was discovered. Extensive structure-activity relationship studies suggest that the entire quinazolinone structure was required, but activity was further enhanced by halide or small hydrophobic substituents at position 6. These analogues did not substantially interfere with the binding of radiolabeled colchicine, vinblastine, or GTP to tubulin and weakly stimulated GTP hydrolysis uncoupled from polymerization. Several analogues have shown in vivo tumor growth inhibitory activity in the L1210 leukemia model, with the lead compound 5o exhibiting good antitumor activity against murine solid tumors as well as human tumor xenografts.

  DOI：

  10.1021/jm00168a029

文献信息

• [EN] AROMATIC NITROGEN-CONTAINING 6-MEMBERED RING COMPOUNDS AND THEIR USE<br/>[FR] COMPOSÉS CYCLIQUES AROMATIQUES AZOTÉS À 6 CHAÎNONS ET LEUR UTILISATION
  申请人：MITSUBISHI TANABE PHARMA CORP

  公开号：WO2010030027A1

  公开（公告）日：2010-03-18

  The present invention provides aromatic nitrogen-containing 6-membered ring compounds having execellent PDE10 inhibitory activity. The present invention relates to an aromatic nitrogen-containing 6-membered ring compound represented by the following formula [I0] or a pharmaceutically acceptable salt thereof, a method for preparing the same, and use of said compounds for PDE10 inhibitors, and a pharmaceutical composition comprising said compounds as an active ingredient: Formula [I0] wherein: X1, X2 and X3 each independently are N or CH, and at least two of X1, X2 and X3 are N; A is *-CH=CH-, *-C(Alk)=CH-, *-CH2-CH2- or *-O-CH2- (* is a bond with R1); Alk is a lower alkyl group; Ring B is an optionally substituted nitrogen-containing aliphatic heterocyclic group; R1 is an optionally substituted nitrogen-containing heterocyclic group, a nitrogen-containing heterocyclic moiety of which is a moiety selected from the group consisting of quinoxalinyl, quinolyl, isoquinolyl, quinazolinyl, pyrazinyl, pyrimidinyl and a moiety thereof fused with a 5 to 6-membered aliphatic ring thereto; Y0 is a group selected from the group consisting of the following (1) to (5): (1) an optionally substituted phenyl or an optionally substituted aromatic monocyclic 5 to 6-membered heterocyclic group; (2) an optionally substituted aminocarbonyl; (3) an optionally substituted amino lower alkyl; (4) -O-R2 wherein R2 is hydrogen, an optionally substituted lower alkyl, lower cycloalkyl, aliphatic monocyclic 5 to 6-membered heterocyclic group, or Formula [AA]; (5) mono- or di-substituted amino; provided that, when Y0 is mono- or di-substituted amino, the nitrogen-containing heterocyclic moiety of R1 is not quinoxalinyl or quinolyl.

  本发明提供了具有出色的PDE10抑制活性的芳香氮含6元环化合物。本发明涉及以下式[I0]所代表的芳香氮含6元环化合物或其药学上可接受的盐，其制备方法，以及将所述化合物用作PDE10抑制剂，以及包含所述化合物作为活性成分的药物组合物：式[I0]其中：X1、X2和X3各自独立地为N或CH，并且至少两个X1、X2和X3为N；A为*-CH=CH-，*-C(Alk)=CH-，*-CH2- -或*-O- -（*为与R1的键）；Alk为低碳烷基基团；环B为可选择取代的含氮脂肪杂环基团；R1为可选择取代的含氮杂环基团，其中的氮杂环基团为从喹喔啉基，喹啉基，异喹啉基，喹唑啉基，吡嗪基，嘧啶基中选取的基团，或者与其中的5至6元脂环融合的基团；Y0为从以下（1）到（5）组成的基团：（1）可选择取代的苯基或可选择取代的芳香单环5至6元杂环基团；（2）可选择取代的氨基羰基；（3）可选择取代的氨基低碳烷基；（4）-O-R2其中R2为氢，可选择取代的低碳烷基，低环烷基，脂肪单环5至6元杂环基团，或式[AA]；（5）单取代或双取代氨基；但是，当Y0为单取代或双取代氨基时，R1的含氮杂环基团不是喹喔啉基或喹啉基。
• A Direct Method for Synthesis of Quinoxalines and Quinazolinones Using Epoxides as Alkyl Precursor
  作者：Xueyan Lv、Lili Lv、Shichen Li、Chengcheng Ding、Bingchuan Yang、Chen Ma

  DOI：10.3390/molecules28217391

  日期：——

  An iodine-mediated one-pot synthesis of pyrrolo/indolo [1,2-a]quinoxalines and quinazolin-4-one via utilizing epoxides as alkyl precursors under metal-free conditions has been described. Both 1-(2-aminophenyl)-pyrrole and 2-aminobenzamide could be applied to this protocol. A total of 33 desired products were obtained with moderate to good yields. This methodology was suitable for wide-scale preparation

  描述了在无金属条件下利用环氧化物作为烷基前体，碘介导的吡咯并/吲哚[1,2-a]喹喔啉和喹唑啉-4-酮的一锅法合成。1-(2-氨基苯基)-吡咯和2-氨基苯甲酰胺都可以应用于该方案。总共获得了 33 种所需产物，收率中等至良好。该方法适合大规模制备，所得产品可以进一步修饰为有前景的药物活性试剂。
• JIANG, J. B.;HESSON, D. P.;DUSAK, B. A.;DEXTER, D. L.;KANG, G. J.;HAMEL, +, J. MED. CHEM., 33,(1990) N, C. 1721-1728
  作者：JIANG, J. B.、HESSON, D. P.、DUSAK, B. A.、DEXTER, D. L.、KANG, G. J.、HAMEL, +

  DOI：——

  日期：——
• AROMATIC NITROGEN-CONTAINING 6-MEMBERED RING COMPOUNDS AND THEIR USE
  申请人：Mitsubishi Tanabe Pharma Corporation

  公开号：EP2342191B1

  公开（公告）日：2013-03-20