Synthesis and evaluation of analgesic, anti-inflammatory and ulcerogenic activities of some triazolo- and 2-pyrazolyl-pyrido[2,3-d]-pyrimidines

Abstract

New series of 2-hydrazino-7,8-dihydro-6H-cyclopenta[5,6]pyrido[2,3-d]pyrimidines and its 1,7,8,9-tetrahydrocyclopenta[5,6]pyrido[2,3-d][1,2,4]triazolo[4,3-a]pyrimidine, 1,7,8,-9-tetrahydrocyclopenta[5,6]pyrido[2,3-d][1,2,3,4]tetrazolo[4,5-a]pyrimidine, 8,9-dihydro-7H-cyclopenta[5,6]pyrido[2,3-d]imidazolo[1,2-a]pyrimidine, 2-(pyrazol-1-yl)-7,8-dihydro-6H-cyclopenta[5,6]pyrido[2,3-d]pyrimidine derivatives were prepared in order to obtain new compounds with potential anti-inflammatory and analgesic activity and low ulcerogenic effect. The compounds possessing potent anti-inflammatory activity were further tested for their analgesic and ulcerogenic activities. Compounds 3-amino-6-(4-aryl)-9-(4-arylmethylene)-cyclopenta[5,6]pyrido[2,3-d][1,2,4]triazolo[4,3-a]pyrimidin-5(H)-one (4c), 1-amino-2-methyl-6-(4-aryl)-9-(4-aryl-methylene)-cyclopenta[5,6]pyrido[2,3-d]imidazolo[1,2-a]pyrimidin-5(H)-one (6a), 2-amino-5-(4-aryl)-8-(4-arylmethylene)-cyclopenta[5,6]pyrido[2,3-d]pyrimidine-4(H)-one (9), 2-(3-amino-5-hydroxypyrazol-1-yl)-5-(4-aryl)-8-(4-arylmethylene)-cyclopenta[5,6]-pyrido[2,3-d]pyrimidin-4(H)-one (10a) and 3-thioxo-6-(4-aryl)-9-(4-arylmethylene)-cyclopenta[5,6]pyrido[2,3-d][1,2,4]triazolo[4,3-a]pyrimidin-5(H)-one (13) showed significant analgesic effects. Compound 2-(3-amino-5-hydroxypyrazol-1-yl)-5-(4-aryl)-8-(4-arylmethylene)-cyclopenta[5,6]pyrido[2,3-d]pyrimidin-4(H)-one (10a) was evaluated as the lead compound having higher anti-inflammatory activity (82.8%) than ibuprofen (79.5%) and lower ulcerogenic effect.U radu je opisana sinteza serije 2-hidrazino-7,8-dihidro-6H-ciklopenta[5,6]pirido[2,3-d]pirimidina i njihovih 1,7,8,9-tetrahidrociklopenta[5,6]pirido[2,3-d][1,2,4]triazolo[4,3-a]pirimidinskih, 1,7,8,9-tetrahidrociklopenta[5,6]pirido[2,3-d][1,2,3,4]tetrazolo[4,5-a]pirimidinskih, 8,9-dihidro-7H-ciklopenta[5,6]pirido[2,3-d]imidazolo[1,2-a]pirimidinskih i 2-(pirazol-1-il)-7,8-dihidro-6H-ciklopenta[5,6]pirido[2,3-d]pirimidinskih derivata s potencijalnim protuupalnim i analgetskim te manjim ulcerogenim djelovanjem. Spojevima s izraženim protuupalnim djelovanjem testirano je analgetsko i ulcerogeno djelovanje. Spojevi 3-amino-6-(4-aril)-9-(4-arilmetilen)-ciklopenta[5,6]pirido[2,3-d][1,2,4]triazolo[4,3-a]pirimidin-5(H)-on (4c), 1-amino-2-metil-6-(4-aril)-9-(4-aril-metilen)-ciklopenta[5,6]pirido[2,3-d]imidazolo[1,2-a]pirimidin-5(H)-on (6a), 2-amino-5-(4-aril)-8-(4-arilmetilen)-ciklopenta[5,6]pirido[2,3-d]pirimidin-4(H)-on (9), 2-(3-amino-5-hidroksipirazol-1-il)-5-(4-aril)-8-(4-arilmetilen)- ciklopenta[5,6]-pirido[2,3-d]pirimidin-4(H)-on (10a) i 3-tiokso-6-(4-aril)-9-(4-arilmetilen)-ciklopenta[5,6]pirido[2,3-d][1,2,4]triazolo[4,3-a]pirimidin-5(H)-on (13) pokazali su značajno analgetsko djelovanje. Spoj 2-(3-amino-5-hidroksipirazol-1-il)-5-(4-aril)-8-(4-arilmetilen)-ciklopenta[5,6]pirido[2,3-d]pirimidin-4(H)-on (10a) je vodeći spoj s jačim protuupalnim djelovanjem (82,8%) od ibuprofena (79,5%), a slabijim ulcerogenim djelovanjem