Design and synthesis of novel 2-phenyl-5-(1,3-diphenyl-1H-pyrazol-4-yl)-1,3,4-oxadiazoles as selective COX-2 inhibitors with potent anti-inflammatory activity.
A novel series of 2-phenyl-5-(1,3-diphenyl-1H-pyrazol-4-yl)-1,3,4-oxadiazoles were designed and synthesized for selective COX-2 inhibition with potent anti-inflammatory activity. Among the compounds tested, 9g (2-(3-(4-nitrophenyl)-1-phenyl-1H-pyrazol-4-yl)-5-phenyl-1,3,4-oxadiazole) was found to be the most potent inhibitor of COX-2 with IC50 of 0.31 μM showing promising degree of anti-inflammatory activity in the carrageenan-induced rat paw edema model with ED50 of 74.3 mg/kg. The lead compound 9g further showed suppression of acetic acid-induced writhes comparable to that of aspirin and gastro-sparing profile superior to the aspirin. Molecular docking analysis displayed higher binding affinity of ligands towards COX-2 than COX-1.
School of Pharmaceutical Sciences, Shoolini University, Solan, Himachal Pradesh, India. Electronic address: bansalsumit50@gmail.com.
Sumit
S
Bansal
School of Pharmaceutical Sciences, Jaipur National University, Jaipur 302017, India.
Manju
M
Bala
Department of Pharmaceutical Chemistry, Manipal College of Pharmaceutical Sciences, Manipal 576104, India. Electronic address: sharadpune_2009@yahoo.com.
Sharad Kumar
SK
Suthar
Doon Valley Institute of Pharmacy and Medicine, Karnal, Haryana 132001, India.
Shivani
S
Choudhary
School of Pharmaceutical Sciences, Shoolini University, Solan, Himachal Pradesh, India.
Shoumyo
S
Bhattacharya
Department of Pharmaceutical Chemistry, ASBASJSM College of Pharmacy, Bela, Ropar, Punjab 140111, India.
Varun
V
Bhardwaj
Department of Pharmaceutical Chemistry, Rajendra Institute of Technology & Sciences, Sirsa, Haryana, India.
Sumit
S
Singla
Department of Pharmaceutical Chemistry, Manipal College of Pharmaceutical Sciences, Manipal 576104, India.
Alex
A
Joseph
D000700:Analgesics / Q000009:adverse effects / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology*; D060326:Chemistry Techniques, Synthetic; D051545:Cyclooxygenase 1 / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000737:chemistry / Q000378:metabolism*; D052246:Cyclooxygenase 2 Inhibitors / Q000009:adverse effects / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D008297:Male; D051379:Mice; D062105:Molecular Docking Simulation; D010069:Oxadiazoles / Q000009:adverse effects / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology*; D011487:Protein Conformation; D051381:Rats; D013276:Stomach Ulcer / Q000139:chemically induced; D013329:Structure-Activity Relationship; D013379:Substrate Specificity
D000700:Analgesics; D000894:Anti-Inflammatory Agents, Non-Steroidal; D052246:Cyclooxygenase 2 Inhibitors; D010069:Oxadiazoles; C583463:1,3,4-oxadiazole; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2
1,3,4-Oxadiazole; Analgesic; Anti-inflammatory; COX-2; Molecular docking analysis; Pyrazole