An efficient and environmental benign solvent-free synthesis of
5-amino-3-aryl-1-(6'-chloropyridazin-3'-yl)pyrazoles
(4a-e) was accomplished by grinding 3-chloro-6-hydrazinopyridazine
(2) and β-ketonitriles (3a-e) in the presence of
p-toulenesulfonic acid as a catalyst. Subsequently, 6'-chloro
group in 4a-e was replaced with cyclic 2° amine derivatives
viz. pyrrolidine 5a, piperidine 5b and morpholine
5c to obtain 6a-e, 7a-e, 8a-e respectively. The
newly synthesized compounds were characterized by using IR, NMR (1H
and 13C), mass spectral studies, elemental analyses. All the
synthesized compounds were studied for their docking interaction with target
protein 6COX and screened for their in vivo analgesic mode of action
against swiss albino mice (animal model) using acetic-acid induced writhing
test. Consequently, docking simulations data justifies the potential of
synthesized series as an analgesic and very well correlated with in vivo
study. Preliminary results revealed that most of the synthesized compounds
exhibited moderate to good analgesic activity as compared to
reference/standard drug (s) sodium diclofenac and candidates 4d
and 7c protrude out as a promising lead for further investigation.