VUF-5087
Chemical Name: 6-Chloro-4-oxo-2-[3-[2(E)-(2-quinolyl)vinyl]phenyl]-4H-1-benzopyran-8-carboxylic acid
CAS No. 205875-33-8
项目整合开发状态: Preclinical
项目研究机构: Vrije Universiteit (Originator)
合成路线:By condensation of 4-(2-quinolinylmethoxy)benzaldeyde (I) with 2-hydroxy-5(1H-tetrazol-5-yl)acetophenone (II) by means of KOH in ethanol/water.The intermediates (I) and (II) have been obtained as follows:Benzaldehyde (I): By condensation of 2-(chloromethyl)quinoline (III) with 4-hydroxybenzaldehyde (IV) by means of K2CO3 in hot DMF.Acetophenone (II): The acetylation of 4-hydroxybenzonitrile (V) with acetic anhydride/sulfuric acid and AlCl3 gives 5-cyano-2-hydroxyacetophenone (VI),which is then cyclized with sodium azide and ammonium chloride in hot DMF.
合成路线:The intermediate acetophenone (III) was prepared from 5-chlorosalicylic acid (I) by O-acetylation with acetic anhydride and a catalytic amount of sulfuric acid,followed by Fries rearrangement of the resulting acetate (II) on heating with aluminum chloride.Condensation of 2-methylquinoline (IV) with an excess of 1,3-benzene dicarboxaldehyde (V) in a refluxing mixture of acetic anhydride and xylene provided aldehyde (VI),which was then condensed with acetophenone (III) by treatment with KOH in a mixture of ethanol and tetrahydrofuran to give chalcone (VII).Finally,oxidative ring closure by refluxing with selenium dioxide in dioxan yielded the desired flavone.
📌 参考资料/链接：
参考文献标题:Synthesis and structure - activity relationships of carboxylated chalcones: A novel series of CysLT1 (LTD4) receptor antagonists
文献作者:Zwaagstra,M.E.; Timmerman,H.; Tamura,M.; Tohma,T.; Wada,Y.; Onogi,K.; Zhang,M.Q.
参考来源:J Med Chem 1997,40(7),1075
📄 详细内容
合成路线:The intermediate acetophenone (III) was prepared from 5-chlorosalicylic acid (I) by O-acetylation with acetic anhydride and a catalytic amount of sulfuric acid,followed by Fries rearrangement of the resulting acetate (II) on heating with aluminum chloride.Condensation of 2-methylquinoline (IV) with an excess of 1,3-benzene dicarboxaldehyde (V) in a refluxing mixture of acetic anhydride and xylene provided aldehyde (VI),which was then condensed with acetophenone (III) by treatment with KOH in a mixture of ethanol and tetrahydrofuran to give chalcone (VII).Finally,oxidative ring closure by refluxing with selenium dioxide in dioxan yielded the desired flavone.
参考文献标题:Synthesis and structure-activity relationships of carboxyflavones as structurally rigid CysLT1 (LTD4) receptor antagonists
文献作者:Zwaagstra,M.E.; Timmerman,H.; van de Stolpe,A.C.; de Kanter,F.J.; Tamura,M.; Wada,Y.; Zhang,M.Q.
参考来源:J Med Chem 1998,41(9),1428