Novel 5-substituted 1H-tetrazoles as cyclooxygenase-2 (COX-2) inhibitors

Al‐Hourani, Baker Jawabrah; Sharma, Sai Kiran; Suresh, Mavanur R.; Wuest, Frank

doi:10.1016/j.bmcl.2012.01.093

Cited by 37 publications

(14 citation statements)

References 12 publications

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“…COX-1 and COX-2 use identical catalytic mechanism to catalyse the same reactions by sharing the same substrates and producing the same products. They are very similar in their protein tertiary conformation as demonstrated from their X-ray crystal structures 38 . These similarities in the structure of both COX isoforms represent a great challenge for the development of selective COX-2 inhibitors.…”

Section: Introductionmentioning

confidence: 81%

“…Two distinct isoforms of COX enzyme are present, a constitutive form (COX-1), associated with several side effects such as haemorrhagia and gastrointestinal (GI) ulceration, and an inducible form (COX-2) which is different in the regulation and tissue distribution from COX-1 [34][35][36] . In 2012, AlHourani et al reported a novel COX-1 splice variant termed as COX-3 37 . COX-1 and COX-2 use identical catalytic mechanism to catalyse the same reactions by sharing the same substrates and producing the same products.…”

Section: Introductionmentioning

confidence: 99%

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

Lamie

Philoppes

Azouz

et al. 2017

Journal of Enzyme Inhibition and Medicinal Chemistry

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Nineteen new compounds containing tetrazole and/or cyanamide moiety have been designed and synthesised. Their structures were confirmed using spectroscopic methods and elemental analyses. Anti-inflammatory activity for all the synthesised compounds was evaluated in vivo . The most active compounds 4c , 5a , 5d–f , 8a and b and 9a and b were further investigated for their ulcerogenic liability and analgesic activity. Pyrazoline derivatives 9b and 8b bearing trimethoxyphenyl part and SO 2 NH 2 or SO 2 Me pharmacophore showed equal or nearly the same ulcerogenic liability (UI: 0.5, 0.75, respectively), to celecoxib (UI: 0.50). Most of tested compounds showed potent central and/or peripheral analgesic activities. Histopathological investigations were done to evaluate test compounds effect on rat's gastric tissue. The obtained results were in consistent with the in vitro data on COX evaluation. Docking study was also done for all the target compounds inside COX-2-active site.

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Section: Introductionmentioning

confidence: 81%

Section: Introductionmentioning

confidence: 99%

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

Lamie

Philoppes

Azouz

et al. 2017

Journal of Enzyme Inhibition and Medicinal Chemistry

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“…Moreover, the presence of electron withdrawing group in one of the aryl substitutions in the para position is more preferable than corresponding electron donating group [18]. Various previous studies were implemented to synthesize selective COX-2 inhibitors by using different methods [18][19][20][21][22]. e reported syntheses are commonly complex which makes the production costs more expensive and beyond the reach of an ordinary person.…”

Section: Introductionmentioning

confidence: 99%

Synthesis, Biological Activity, and Molecular Modeling Studies of Pyrazole and Triazole Derivatives as Selective COX-2 Inhibitors

Assali

Abualhasan

Sawaftah

et al. 2020

Journal of Chemistry

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Series of diaryl-based pyrazole and triazole derivatives were designed and synthesized in a facile synthetic approach in order to produce selective COX-2 inhibitor. ese series of derivatives were synthesized by different reactions like Vilsmeier-Haack reaction and click reaction. In vitro COX-1 and COX-2 inhibition studies showed that five compounds were potent and selective inhibitors of the COX-2 isozyme with IC 50 values in 0.551-0.002 μM range. In the diarylpyrazole derivatives, compound 4b showed the best inhibitory activity against COX-2 with IC 50 � 0.017 μM as one of the N-aromatic rings was substituted with sulfonamide and the other aromatic ring was unsubstituted. However, when the N-aromatic ring was substituted with sulfonamide and the other aromatic ring was substituted with sulfone (compound 4d), best COX-2 selectivity was achieved (IC 50 � 0.098 μM, SI � 54.847). In the diaryltriazole derivatives, compound 15a showed the best inhibitory activity in comparison to all synthesized compounds including the reference celecoxib with IC 50 � 0.002 μM and SI � 162.5 as it could better fit the extra hydrophobic pocket which is present in the COX-2 enzyme. Moreover, the docking study supports the obtained SAR data and binding similarities and differences on both isozymes.

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“…The present studies aim to interpret structure, spectra and molecular properties of a steroidal tetrazole, 7a-Aza-B-homostigmast-5-eno [7a,7-d] that exhibits remarkable antimicrobial and cytotoxic activities [1]. Tetrazole constitutes a class of nitrogen containing heterocyclic compounds exhibiting robust biological activities [1][2][3][4][5][6][7]. Recently, tetrazole and its derivatives have successfully been employed as carboxylic acid isosteres.…”

Section: Introductionmentioning

confidence: 99%

DFT, Hirshfeld surfaces, spectral and in vivo cytotoxic studies of 7a-Aza-B-homostigmast-5-eno [7a,7-d] tetrazole

Alam

Nami

Khan

et al. 2015

Journal of Molecular Structure

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Novel 5-substituted 1H-tetrazoles as cyclooxygenase-2 (COX-2) inhibitors

Cited by 37 publications

References 12 publications

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

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

Synthesis, Biological Activity, and Molecular Modeling Studies of Pyrazole and Triazole Derivatives as Selective COX-2 Inhibitors

DFT, Hirshfeld surfaces, spectral and in vivo cytotoxic studies of 7a-Aza-B-homostigmast-5-eno [7a,7-d] tetrazole

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