Versatile synthesis of functionalised dibenzothiophenes via Suzuki coupling and microwave-assisted ring closure
作者:Sonsoles Rodriguez-Aristegui、Kate M. Clapham、Lauren Barrett、Céline Cano、Marine Desage-El Murr、Roger J. Griffin、Ian R. Hardcastle、Sara L. Payne、Tommy Rennison、Caroline Richardson、Bernard T. Golding
DOI:10.1039/c1ob05282a
日期:——
5-tetramethyl-1,3,2-dioxaborolan-2-yl)-4H-chromen-4-one to give the respective 6-, 7-, 8- or 9-substituted dibenzothiophen-4-ylchromenones. These compounds were evaluated as inhibitors of DNA-dependent protein kinase (DNA-PK) and compared to the parent 8-(dibenzo[b,d]thiophen-4-yl)-2-morpholin-4-yl-4H-chromen-4-one. Notably, derivatives bearing hydroxy or methoxy substituents at C-8 or C-9 retained activity
通过2,6-二溴苯胺与苯基硼酸(被Me,NO 2,OH,OMe或Cl取代)的Suzuki交叉偶联,获得氨基取代的联苯,优选在微波辐射的辅助下进行。氨基转化为硫醇之前,先进行碱诱导的分子内取代,然后通过微波加热促进其生成目标二苯并噻吩的第二个C–S键。将所获得的1-,2-,3-或4-取代的6-卤代二苯并噻吩与2-吗啉-4--4-基-8-(4,4,5,5-四甲基-1,3)进行钯介导的偶联,2-二氧杂硼烷-2-基)-4 H-chromen-4-one给出各自的6-,7-,8-或9-取代的二苯并噻吩-4-基色农酮。这些化合物被评估为DNA依赖性蛋白激酶(DNA-PK)的抑制剂,并与母体8-(dibenzo [ b,d ] thiophen-4-yl)-2-morpholin-4-yl-4 H -chromen进行了比较。 -4-一 值得注意的是,在C-8或C-9上带有羟基或甲氧基取代基的衍生物保留