Synthesis, docking studies and anti-inflammatory activity of some 2-amino-5,6,7,8-tetrahydroquinoline-3-carbonitriles and related compounds.
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.
Applied Organic Chemistry Department, National Research Centre, Dokki, Cairo 12622, Egypt. oiel_salam@yahoo.com
O I
OI
Abd El-Salam
D A
DA
Abou El Ella
N S M
NS
Ismail
M
M
Abdullah
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000138:chemical synthesis* / Q000494:pharmacology* / Q000633:toxicity; D002351:Carrageenan; D015232:Dinoprostone / Q000097:blood; D004487:Edema / Q000139:chemically induced / Q000517:prevention & control; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology; D007202:Indicators and Reagents; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D009570:Nitriles / Q000138:chemical synthesis* / Q000494:pharmacology* / Q000633:toxicity; D011804:Quinolines / Q000138:chemical synthesis* / Q000494:pharmacology* / Q000633:toxicity; D051381:Rats; D013055:Spectrophotometry, Infrared; D013276:Stomach Ulcer / Q000139:chemically induced / Q000473:pathology; D013329:Structure-Activity Relationship; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors
D000893:Anti-Inflammatory Agents; D004791:Enzyme Inhibitors; D007202:Indicators and Reagents; D009570:Nitriles; D011804:Quinolines; D002351:Carrageenan; D048051:p38 Mitogen-Activated Protein Kinases; D015232:Dinoprostone