Imidazola ciklu saturošu termošoka proteīna Hsp90 inhibitoru sintēzes pētījumi

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Latvijas Universitāte

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Darba mērķis bija izstrādāt 1-alkil-2-arilmetil-1H-tiēno[2,3-d]-imidazol-5-karbonskābes un to atvasinājumu iegūšanas metodes no 1-alkil-2-arilmetil-4-brom-1H-imidazol-5-karbaldehīdiem. Darbā pētītas šo intermediātu sintēzes iespējas no tādām komerciāli pieejamām izejvielām kā 2,4,5-tribromimidazols un arilacetonitrila atvasinājumi. Sekmīgi veiktas sintezēto 1-alkil-2-arilmetil-4-brom-1H-imidazol-5-karbaldehīdu sametināšanas reakcijas ar 2-merkaptoacetamīdu un etil-2-merkaptoacetātu, un tālāka iegūto sametināšanas produktu ciklizācija par attiecīgajiem 1-alkil-2-arilmetil-1H-tiēno[2,3-d]-imidazol-5-karbonskābes atvasinājumiem, izmantojot gan parasto sildīšanu, gan mikroviļņu tehnoloģiju.
The aim of the present work was to elaborate methods of the preparation of 1-alkyl-2-arylmethyl-1H-thieno[2,3-d]-imidazole-5-carboxylic acids and their derivatives from 1-alkyl-2-arylmethyl-4-bromo-1H-imidazole-5-carbaldehydes. The possibilities of synthesis of these intermediates from such commercially available starting materials as 2,4,5-tribromoimidazole and arylacetonitrile derivatives were studied. Successful experiments of the coupling reaction of prepared 1-alkyl-2-arylmethyl-4-bromo-1H-imidazole-5-carbaldehydes with 2-mercaptoacetamide and ethyl 2-mercaptoacetate followed by the cyclization of the obtained coupling products into the corresponding derivatives of 1-alkyl-2-arylmethyl-1H-thieno[2,3-d]-imidazole-5-carboxylic acids both by routine heating and microwave technique were performed.

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