Synthesis, characterization and preliminary screening of regioisomeric 1-(3-pyridazinyl)-3-arylpyrazole and 1-(3-pyridazinyl)-5-arylpyrazole derivatives towards cyclooxygenase inhibition.
In a search for novel compounds with analgesic and anti-inflammatory activity, a series of regioisomeric 1-(3-pyridazinyl)-3-arylpyrazole (5a-f, 6a-f) and 1-(3-pyridazinyl)-5-arylpyrazole (7a-f, 8a-f) derivatives were synthesized. The structure of these regioisomers was confirmed by spectral techniques. The compounds were preliminarily screened at 8 microM concentration for their inhibitory activity against cyclooxygenase enzymes, COX-1 and COX-2, using a human whole blood test. The tested derivatives showed inhibitory activity for both enzymes and are worthy of further investigation for developing better leads.
Unlü
Serdar
S
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Gazi University, Etiler, Ankara 06330, Turkey. sunlu@gazi.edu.tr
Banoglu
Erden
E
Ito
Shigeru
S
Niiya
Tokihiro
T
Eren
Gökçen
G
Okçelik
Berna
B
Sahin
Mustafa Fethi
MF
D051545:Cyclooxygenase 1 / Q000097:blood; D051546:Cyclooxygenase 2 / Q000097:blood; D052246:Cyclooxygenase 2 Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D016861:Cyclooxygenase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D004353:Drug Evaluation, Preclinical; D006801:Humans; D066298:In Vitro Techniques; D007536:Isomerism; D009682:Magnetic Resonance Spectroscopy; D008565:Membrane Proteins / Q000037:antagonists & inhibitors / Q000097:blood; D011720:Pyrazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D008565:Membrane Proteins; D011720:Pyrazoles; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496511:PTGS1 protein, human; C496540:PTGS2 protein, human