Synthesis, biological evaluation and molecular docking of novel series of spiro [(2H,3H) quinazoline-2,1'- cyclohexan]-4(1H)- one derivatives as anti-inflammatory and analgesic agents.
Three series of Spiro [(2H,3H) quinazoline-2,1'-cyclohexan]-4(1H)-one derivatives have been synthesized. Some of the novel quinazolinone derivatives IIe, VIIIc, XIc, XIIb, XIIc, XVIb showed considerable potent anti-inflammatory and analgesic activity of superior G.I.T. safety profile in experimental rats in comparing to indomethacin and tramadol as reference drugs. Docking study into COX-2 has been made for derivatives of highest anti-inflammatory activity. The compound XVIb showed the nearest RMSD value to that of indomethacin.
Amin
K M
KM
Depatment of Therapeutical Chemistry, Faculty of Pharmacy, Cairo University, Egypt.
Kamel
M M
MM
Anwar
M M
MM
Khedr
M
M
Syam
Y M
YM
D000700:Analgesics / Q000009:adverse effects / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000009:adverse effects / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology*; D003510:Cyclohexanes / Q000737:chemistry; D003512:Cyclohexanones / Q000009:adverse effects / Q000138:chemical synthesis* / Q000494:pharmacology*; D051546:Cyclooxygenase 2 / Q000737:chemistry / Q000378:metabolism; D004487:Edema / Q000188:drug therapy; D005260:Female; D008297:Male; D008958:Models, Molecular; D008968:Molecular Conformation; D011799:Quinazolines / Q000009:adverse effects / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats; D014456:Ulcer / Q000139:chemically induced
D000700:Analgesics; D000893:Anti-Inflammatory Agents; D003510:Cyclohexanes; D003512:Cyclohexanones; D011799:Quinazolines; C550826:spiro((2H,3H)quinazoline-2,1'-cyclohexan)-4(1H)-one; C506365:Cyclohexane; D051546:Cyclooxygenase 2