Synthesis and preliminary pharmacological screening of 2,4-disubstituted N,N-dialkyl-1,8-naphthyridine-3-carboxamides
Di Braccio, M.; Roma, G.; Balbi, A.; Sottofattori, E.; Carazzone, M.
Farmaco 44(9): 865-881
1989
ISSN/ISBN: 0014-827X PMID: 2604838 Document Number: 346787
By treating at 100 degrees C 2-aminonicotinic acid with ethyl N,N-dialkylmalonamate (I) and phosphorus oxychloride N,N-dialkyl-4-chloro-1,2-dihydro-2-oxo-1,8-naphthyridine- 3-carboxamides (II) were obtained. The reaction of compounds (II) with an excess of refluxing phosphorus oxychloride afforded N,N-dialkyl-2,4-dichloro-1,8-naphthyridine-3-carboxamides (III), which in turn were treated at room temperature with excess primary amines to give a mixture of isomeric N,N-dialkyl-2-(alkylamino or cycloalkylamino)-4-chloro-1,8-naphthyridine-3-carboxamides (IV) and N,N-dialkyl-4-(alkylamino or cycloalkylamino)-2-chloro-1,8-naphthyridine-3-carboxamides (V). When this last reaction was performed at 160 degrees C, only N,N-dialkyl-2,4-bis(alkylamino or cycloalkylamino)-1,8-naphthyridine-3-carboxamides (VI) were obtained; under the same conditions (IV c) or (V c) reacted with methylamine to give isomeric 2,4-bis(alkylamino)derivatives (VII) or (VIII), respectively. Compounds (II b), (III b), (IV a,c,d), (V a,c,d) were submitted to a wide preliminary pharmacological screening. Some of them, depending on the structure, showed antihypertensive [(IV c)], anti-inflammatory [(IV c) greater than (III b)], or, in the behavioral test, anti-aggressive [(IV d) greater than (III b)] activity. Furthermore compound (III b) caused moderate inhibition of the 5-HT induced contraction of the guinea-pig ileum.