Synthesis of new thiazolo-celecoxib analogues as dual cyclooxygenase-2/15-lipoxygenase inhibitors: Determination of regio-specific different pyrazole cyclization by 2D NMR

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). [Display omitted] •New thiazolo-celecoxib analogues were designed and synthesized.•Thiazolo-celecoxib drug hybrid showed higher COX-2/15-LOX inhibition properties.•Designed compounds were evaluated as anti-inflammatory activity using Carrageenan-induced rat paw edema and proved activity.•Ulcer liability index of compounds was determined and they showed higher safety profiles.•Most of the compounds were effective as anti-inflammatory and more selective towards COX-2/15-LOX.