title: Synthesis of new thiazolo-celecoxib analogues as dual cyclooxygenase-2/15-lipoxygenase inhibitors: Determination of regio-specific different pyrazole cyclization by 2D NMR.
abstract: Two new series of 1,5-diaryl pyrazoles (5a, 5b, 7a, 7b and 10) and 1,5-diaryl pyrazoline (12a and 12b) were prepared as both Cyclooxygenase-2 and 15-lipoxygenase inhibitors. Carrageenan-induced rat paw edema, ulcer index and anti-COX-1/COX-2 and 15-LOX inhibition assays were also included. Cyclization of different pyrazoles was discussed using 2D NMR such as HSQC, HMBC and NOSEY determinations. Compound 5a is more effective with ED50 = 0.98 and 3.98 μM against COX-2 and 15-lipoxygenase respectively, than the references celecoxib (1.54 μM) and meclofenamate sodium (5.64 μM).
authors.affiliation: Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Beni-Suef University, Beni-Suef, 62514, Egypt. Electronic address: eman.ahmed@pharm.bsu.edu.eg.
authors.forename: Eman K A
authors.initials: EK
authors.lastname: Abdelall
authors.affiliation: Pharmacology Department, Faculty of Veterinary, Cairo University, Cairo, Egypt.
authors.forename: Gehan M
authors.initials: GM
authors.lastname: Kamel
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D001093:Arachidonate 15-Lipoxygenase / Q000378:metabolism*; D002417:Cattle; D000068579:Celecoxib / Q000009:adverse effects / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D060326:Chemistry Techniques, Synthetic; D003500:Cyclization; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D052246:Cyclooxygenase 2 Inhibitors / Q000009:adverse effects / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D016859:Lipoxygenase Inhibitors / Q000009:adverse effects / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D011720:Pyrazoles / Q000737:chemistry*; D051381:Rats; D013237:Stereoisomerism; D013844:Thiazoles / Q000737:chemistry*; D014456:Ulcer / Q000139:chemically induced
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D052246:Cyclooxygenase 2 Inhibitors; D016859:Lipoxygenase Inhibitors; D011720:Pyrazoles; D013844:Thiazoles; C031280:pyrazole; D001093:Arachidonate 15-Lipoxygenase; D051546:Cyclooxygenase 2; D000068579:Celecoxib
keywords: 15-Lipoxygenase inhibitors; Anti-inflammatory; Celecoxib analogues; Cyclooxygenase inhibitors; DMFDMA; Ethyl trifloroacetate; SO(2)NH(2) pharmacophores