Synthesis of pyrimidine and condensed pyrimidine derivatives and their evaluation for anti-inflammatory activity

Abstract

Condensation of various amines (Ia-c) with 4-isothiocyanato-4-methyl-2- pentanone (2a) at room temperature gave tetrahydropyrimidinethiones (3a-c) whereas condensation of 1a-e with 3-isothiocyanatobutanal at room temperature gave tetrahydropyrimidinethiones (4a-e). Amines 1a, d, f-i on condensation with 4-isothiocyanato-4- methyl-2-pentanone (2a) by heating under reflux for 8 h at pH ? 4 (for 1a, d) and at RT (for 1f-i) gave dihydropyrimidinethiones 5a-b and 5c-f, respectively. Condensation of 1f with 3-isothiocyanatobutanal gave dihydropyimidinethione 6. When isothiocyanate (2a) and phenylenediamine derivatives 1g, h were heated under reflux at pH ?4, tricyclic compounds 7a, b were obtained in good yields. Condensation of 3-isothiocyanatobutanal with o-phenylenediamines 1h and 1j at pH ? 5 by refluxing in methanol for 8 h gave products 8 and 9. All these compounds were screened for anti-inflammatory activity. Compounds 3c, 4c and 7a exhibited anti-inflammatory activity comparable to standard drug ibuprofen. © Springer Science+Business Media, LLC 2010.