Synthesis of compounds containing isocoumarin-pyrazole hybridderivatives and investigation of their inhibitory effects on humancarbonic anhydrase isozymes

In this thesis, the synthesis and characterization of a new series of isocoumarin derivatives, isocoumarin-phenylhydrazone, isocoumarin-pyrazole and isocoumarin-chalcone (51 compounds in total), hybrid compounds and inhibition effect of 36 of them on four human carbonic anhydrase (hCA, EC 4.2.1.1) isoforms, (h)CA I, II, IX and XII, were studied. The synthesised isocoumarin derivative compounds were classified into 3 different groups. The 1st group isocoumarin derivatives were coded as (X(1-20)), the 2nd group isocoumarin derivatives were coded as (4a-4p) and the 3rd group isocoumarin derivatives were coded as (5a-5o). For this purpose, a total of 20 compounds, group 1 isocoumarin derivatives (X(1-20)), including five phenylhydrazone, five 1-phenyl-pyrazole and ten 3-substituted and 3,4-disubstituted isocoumarin derivatives containing pyrazole-substituted pyrimidine trion/thioxo-pyrimidine dion units were first synthesized and characterized. Subsequently, 16 isocoumarin-chalcone hybrids, group 2 isocoumarin derivatives (4a-4p), were synthesized and characterized. Then, 15 new isocoumarin-pyrazole hybrid compounds, group 3 isocoumarin derivatives (5a-5o), were synthesised and characterised by reacting the synthesised isocoumarinchalcone, group 2 isocoumarin derivatives (4a-4p), hybrid compounds with substituted phenyl hydrazine compounds under suitable conditions. The inhibition effects of the synthesized compounds in groups 1 and 2 on human carbonic anhydrase isoforms, (h)CA I, II, IX, and XII, were investigated. Isocoumarins, isomeric to coumarins which act as effective carbonic anhydrase (CA, EC 4.2.1.1) inhibitors, were investigated for the first time in this study as inhibitors of this enzyme. FT-IR, 1HNMR, and 13C-NMR techniques were used for the structural characterization of the compounds synthesized.