Synthesis, docking studies and anti-inflammatory activity of some 2-amino-5,6,7,8-tetrahydroquinoline-3-carbonitriles and related compounds

Abstract

A series of 2-amino-5,6,7,8-tetrahydroquinoline-3-carbonitriles 4a-c has been synthesized and reacted with various reagents. Docking studies into the catalytic site of p38 mitogen activated protein kinase (MAPK) were used to identify potential anti-inflammatory lead compounds. The anticipated lead derivative 2-(pyridin-3-yl)-5-(4-methoxyphenyl)-6,7,8,9-tetrahydropyrimido[4,5- b]quinolin-4-amine 9b was endowed with good binding energy. Also, the obtained products were evaluated for their in vivo antiinflammatory activity as prostaglandin inhibitiors (% inhibition of edema and % inhibition of plasma PGE2 at the two dose levels were determined). The tested compounds exhibited significant anti-inflammatory activity and minor ulcerogenic effects, when compared to the reference standard indomethacin, with product 9b being of particular interest.