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Drug Res (Stuttg) 2020; 70(11): 493-502
DOI: 10.1055/a-1202-9959
Original Article

Design, Synthesis and Biological Evaluation of 5-amino-3-aryl-1-(6'-chloropyridazin-3'-yl)pyrazoles and their Derivatives as Analgesic Agents

Swati,
Ranjana Aggarwal
1   Department of Chemistry, Kurukshetra University, Kurukshetra, India
2   Department of Scientific and Industrial Research NISTADS, New Delhi, India
,
Pawan Kaushik
3   Department of Pharmaceutical Sciences, Kurukshetra University, Kurukshetra, India
,
Ajay Kumar
3   Department of Pharmaceutical Sciences, Kurukshetra University, Kurukshetra, India
,
Deepika Saini
3   Department of Pharmaceutical Sciences, Kurukshetra University, Kurukshetra, India
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Abstract

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.

Key words

analgesic drugs - anti-inflammatory drugs - biopharmaceuticals - drug research

Supplementary Material



Publication History

Received: 24 March 2020

Accepted: 18 May 2020

Article published online:
24 July 2020

© 2020. Thieme. All rights reserved.

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