Synthesis and evaluation of 1,5-diaryl-substituted tetrazoles as novel selective cyclooxygenase-2 (COX-2) inhibitors

Sonochemical synthesis of 5-substituted 1H-tetrazoles catalyzed by ZrP2O7 nanoparticles and regioselective conversion into new 2,5-disubstituted tetrazoles

“…Recently, tetrazole derivatives have been synthesized by various catalysts such as Pd(OAc) 2 -ZnBr 2 [10], Yb(OTf) 3 [11], Zn(OTf) 3 [12], nanocrystalline ZnO, Zn/Al hydrotalcite [13], Zn hydroxyapatite [14], Cu 2 O [15,16], FeCl 3 -SiO 2 [17], CdCl 2 [18], BaWO 4 , γ-Fe 2 O 3 [19], mesoporous ZnS nanospheres [20], ZnS nanoparticles [21], CuFe 2 O 4 nanoparticles [22], copper (II) supported on Fe 3 O 4 @SiO 2 nanoparticles [23] and CoY zeolite [24]. 1,5-Disubstituted tetrazoles are important in biology and medicine as NAD(P)H oxidase inhibitors [25], glucokinase activators [26], hepatitis C virus serine protease NS3 inhibitors [27], selective cyclooxygenase-2 inhibitors [28], calcitonin gene-related peptide receptor antagonists and antimigraine agents [29]. Biological activities of 2,5-disubstituted tetrazoles are also reported such as antiviral and antifungal activities [30,31].…”

Synthesis, cyclooxygenase inhibition and anti-inflammatory evaluation of new 1,3,5-triaryl-4,5-dihydro-1H-pyrazole derivatives possessing methanesulphonyl pharmacophore

“…1 H NMR and 13 C NMR spectra were measured on a Bruker 400 MHz spectrometer (Faculty of Pharmacy, Beni-Suef University, Beni-Suef, Egypt) in D 2 O, DMSO-d 6 with TMS as the internal standard, where J (coupling constant) values were estimated in hertz (Hz). Mass spectra were run on Hewlett Packard 5988 spectrometer.…”

“…While COX-1 enzyme is constitutively expressed and plays an important role as a housekeeping enzyme such as protection of gastric mucosa, vascular homeostasis and platelet aggregation, COX-2 enzyme is expressed and significantly upregulated during acute and chronic inflammation, pain and oncogenesis 2 . Non-selective NSAIDs such as aspirin, ibuprofen and indomethacin inhibit the activities of both enzymes and in turn inhibit the production of gastro protective prostaglandins (PGs) synthesized through COX-1 pathway causing gastro intestinal side effects like ulcers, perforation and bleeding 3 .…”

“…Non-selective NSAIDs such as aspirin, ibuprofen and indomethacin inhibit the activities of both enzymes and in turn inhibit the production of gastro protective prostaglandins (PGs) synthesized through COX-1 pathway causing gastro intestinal side effects like ulcers, perforation and bleeding 3 . For this reason, selective COX-2 inhibitor drugs (coxibs) such as celecoxib (1), rofecoxib (2) and valdecoxib (3) (Figure 1) which have the same anti-inflammatory efficacy as traditional NSAIDs with minimized unwanted gastrointestinal side effects take much consideration in the last two decades 4 . Unfortunately, highly selective COX-2 inhibitors caused cardiovascular side effects such as increased systemic blood pressure and myocardial infarction that ultimately prompted the withdrawal of rofecoxib and valdecoxib 5 .…”

Novel tetrazole and cyanamide derivatives as inhibitors of cyclooxygenase-2 enzyme: design, synthesis, anti-inflammatory evaluation, ulcerogenic liability and docking study

“…It is reduced in COX-1 due to the presence of Ile523 rather than Val523 in COX-2. Conformational change is occurred as a result of the presence of Val523 in COX-2, leading to the formation of additional hydrophobic secondary internal pocket protruding off the primary binding site 39 . A large number of compounds have been synthesised and evaluated for their selective COX-2 inhibitory activity.…”