Future Medicinal Chemistry Research Article part of Future Med. Chem. (Epub ahead of print) ISSN 1756-8919 10.4155/fmc-2016-0240 © 2017 Future Science Ltd Aim: 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. Materials & methods: 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. Results: 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. Graphical abstract 3D representation showing its interaction with COX-1 enzyme active site. Graphical Abstract COX-1/COX-2 Ratio 17.50 Analgesic protection 100% % inhibition of Anti-inflammatory activity 76.16% (2h), 78.1% (3h) N N HOOC HO Cl 3c First draft submitted: 22 December 2016; Accepted for publication: 15 February 2017; Published online: 10 April 2017 Keywords:฀ analgesic฀•฀anti-infammatory฀•฀COX฀inhibition฀•฀imidazole฀•฀imidazo[1,5-a] quinazoline฀•฀Lipinski’s฀parameters Relieving pain is an important target in research as it is a very serious problem included in most of diseases. Pain may be physiological, neuropathic or inflammatory due to infection or tissue damage. Gener- ally, pain can be treated by the use of non- steroidal anti-inflammatory drugs (NSAIDs) or opiates [1] . Opioids are used mainly in Synthesis and molecular docking of new imidazoquinazolinones as analgesic agents and selective COX-2 inhibitors Hassanein H Hassanein 1 , Hanan H Georgey 1 , Marwa A Fouad* ,1 , Ahmed M El Kerdawy 1,2 & Mona F Said 1 1 Department฀of฀Pharmaceutical฀ Chemistry,฀Faculty฀of฀Pharmacy,฀Cairo฀ University,฀Cairo฀11562,฀Egypt 2 Molecular฀Modeling฀Unit,฀Faculty฀of฀ Pharmacy,฀Cairo฀University,฀Kasr฀El-Aini฀ Street,฀Cairo฀11562,฀Egypt *Author฀for฀correspondence:฀ Tel:฀+20฀122฀244฀1198฀ marwa.fouad@pharma.cu.edu.eg For reprint orders, please contact reprints@future-science.com