title: Synthesis and molecular docking of new imidazoquinazolinones as analgesic agents and selective COX-2 inhibitors.
abstract: The discovery of new generation of selective COX-2 inhibitors with potential analgesic and anti-inflammatory activity and minimal side effects is a major interest.
  
  
  
  Novel imidazole and imidazo[1,5-a]quinazoline derivatives were prepared and evaluated for their analgesic and anti-inflammatory activities. COX-1/COX-2 isozyme selectivity testing and molecular docking were performed. Key physicochemical parameters were calculated.
  
  
  
  All tested compounds exhibited significant activities compared with indomethacin as reference drug. Pharmacological evaluation showed that compounds 3c and 14c possess promising analgesic activity, pronouncing anti-inflammatory effect and reasonable COX-2 selectivity. Molecular docking attributed their good activity to their hydrogen bonding interaction with key amino acids in COX isozymes Arg120, Tyr355 and Ser530. Most compounds obeyed 'Lipinski's rule of five' and possess promising pharmacokinetic properties.
authors.affiliation: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Cairo University, Cairo 11562, Egypt.
authors.forename: Hassanein H
authors.initials: HH
authors.lastname: Hassanein
authors.affiliation: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Cairo University, Cairo 11562, Egypt.
authors.forename: Hanan H
authors.initials: HH
authors.lastname: Georgey
authors.affiliation: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Cairo University, Cairo 11562, Egypt.
authors.forename: Marwa A
authors.initials: MA
authors.lastname: Fouad
authors.affiliation: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Cairo University, Cairo 11562, Egypt.|Molecular Modeling Unit, Faculty of Pharmacy, Cairo University, Kasr El-Aini Street, Cairo 11562, Egypt.
authors.forename: Ahmed M
authors.initials: AM
authors.lastname: El Kerdawy
authors.affiliation: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Cairo University, Cairo 11562, Egypt.
authors.forename: Mona F
authors.initials: MF
authors.lastname: Said
mesh_terms: D000700:Analgesics / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D016227:Benzoquinones; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D052246:Cyclooxygenase 2 Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D007093:Imidazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D051379:Mice; D062105:Molecular Docking Simulation; D015394:Molecular Structure; D010146:Pain / Q000139:chemically induced / Q000188:drug therapy*; D013329:Structure-Activity Relationship
chemical_list: D000700:Analgesics; D000894:Anti-Inflammatory Agents, Non-Steroidal; D016227:Benzoquinones; D052246:Cyclooxygenase 2 Inhibitors; D007093:Imidazoles; C004532:quinone; C029899:imidazole; D051546:Cyclooxygenase 2
keywords: COX inhibition; Lipinski's parameters; analgesic; anti-inflammatory; imidazo[1,5-a]quinazoline; imidazole