Synthesis of 4-substituted pyridin-2(1H)-ones, pyridine-2(1H)-thiones, related derivatives as analogues of cardiotonic drug milrinone

A convenient method of synthesis of 4-substituted 5-(4'-pyridyl)pyridine-2( 1H)-ones 9-12 and pyridine-2(1H)-thione 18 was elaborated by a Michael reac tion of 4-pyridylacetone 3 and 2-cyano-3-R-acrylamides (thioamides) 4-6, 13 -14 with subsequent heterocyclization, dehydration and dehydrogenation The sodium salt of thione 19 as a water-soluble compound was obtained by treatm ent of thione 18 with sodium methylate. Alkylation of die salt of 1,4-dihyd ropyridine-2(3H)-thione 16 and pyridinethione 18 yielded the corresponding 2-alkylthioderivatives 21 and 23-24. By treatment of 2-carbamoylmethylthio- 1,4-dihydropyridine 21 with acetic acid 7H-thiazolo[3,2-a]pyridin-3(2H)-one 22 was obtained, but treatment of pyridine 21 with sodium methylate gave t hieno[2,3-b]pyridine 25. The synthesized compounds were screened in vitro f or cardiotonic activity on spontaneously contracted rabbit atria and guinea pig papillary muscle.