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通过合成得到了一系列新颖的苯并[b]氧杂棘-5(2H)-酮类化合物单晶,结构经~1HNMR,~(13)CNMR和HREIMS确证,E-7-[(2,5-二羟基苯基)甲亚基]氨基-3,4-二氢-苯并[b]氧杂棘-5(2H)-酮(8k)和E-7-[(2,3,4-三羟基苯基)亚基]氨基-3,4-二氢-苯并[b]氧杂棘-5-(2H)-酮(8n)的结构经单晶X衍射方法进一步确证.系统测试了化合物对蛋白酪氨酸激酶(PTKs),如ErbB1,ErbB2,c-Met,ALK,FGFR1,RET和KDR等的抑制活性,结果表明含有邻苯二酚片段的化合物对蛋白酪氨酸激酶具有显著的抑制活性,其中E-7-[(3,4-二羟基苯基)甲亚基]氨基-3,4-二氢-苯并[b]氧杂棘-5(2H)-酮(8i)对ErbB1和ErbB2的IC50分别为1.0和0.33μmol/L,8n对RET的IC_(50)为0.7μmol/L,7-[(3,4-二羟基苯基)甲基]氨基-2,3,4,5-四氢-苯并[b]氧杂棘-5-醇(10b)对ErbB2的IC_(50)为1.02μmol/L.
A series of novel single crystals of benzo [b] oxepin-5 (2H) -one were synthesized and their structures were confirmed by ~ 1HNMR, ~ 13CNMR and HREIMS. E-7- [ Dihydroxybenzo [b] oxepin-5 (2H) -one (8k) and E-7 - [(2,3,4 - trihydroxyphenyl) amino] -3,4-dihydro-benzo [b] oxepin-5- (2H) -one (8n) was confirmed by single crystal X-ray diffraction. The inhibitory activity of the compounds on protein tyrosine kinases (PTKs) such as ErbB1, ErbB2, c-Met, ALK, FGFR1, RET and KDR and the like shows that the compound containing the catechol fragment has a With significant inhibitory activity, wherein E-7 - [(3,4-dihydroxyphenyl) methylidene] amino-3,4- dihydro- benzo [b] oxepin-5 (2H) -one 8i) had IC50 of 1.0 and 0.33μmol / L for ErbB1 and ErbB2, respectively, 0.7μmol / L for IC 50 of RET for 8n, and 7 - [(3,4-dihydroxyphenyl) methyl] The IC 50 of 3,4,5-tetrahydro-benzo [b] oxepin-5-ol (10b) to ErbB2 was 1.02 μmol / L.