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.
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Gazi University, Etiler, Ankara 06330, Turkey. sunlu@gazi.edu.tr
Serdar
S
Unlü
Erden
E
Banoglu
Shigeru
S
Ito
Tokihiro
T
Niiya
Gökçen
G
Eren
Berna
B
Okçelik
Mustafa Fethi
MF
Sahin
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