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Synthesis and biological evaluation of imidazo[1,2-\({{\varvec{b}}}\)]pyridazines as inhibitors of TNF-\({\varvec{\upalpha }}\) production

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Abstract

Tumor necrosis factor-alpha (TNF-\(\upalpha )\) is an important pro-inflammatory cytokine responsible for a diverse range of inflammatory diseases including rheumatoid arthritis. In the present manuscript, our medicinal chemistry efforts on the design, synthesis and TNF-\(\upalpha \) evaluation of a series of 3, 6-disubstituted imidazo[1,2-b]pyridazine is described. The best compounds were 3-pyridyl and (4-(methylsulfonyl)phenyl) analogs 8q and 8w, showing inhibition of TNF-\(\upalpha \) production with IC\(_{50 }\)values of 0.9 and 0.4 \(\upmu \)M, respectively. The identified leads have potential for further development for treatment of inflammatory diseases.

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Acknowledgements

MRK thanks Medicinal Chemistry, Analytical Chemistry and Department of Pharmacology of Piramal Enterprises Ltd. Goregaon, Mumbai for analytical and biological studies. Authors are also thankful to the Management and Principal of Padmashri Vikhe Patil College Pravaranagar for providing all necessary facilities. SSP thanks to UGC, New Delhi, INDIA for financial assistance wide file no. 47-618/13 (WRO) dated 20/05/2014.

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Authors and Affiliations

  1. Department of Chemistry, Post Graduate and Research Centre, Padmashri Vikhe Patil College of Arts, Science and Commerce, Pravaranagar, A/P Loni, Tal. Rahata, Dist., Ahmednagar, 413713, India

    Shivaji S. Pandit, Mahesh R. Kulkarni, Yashwant B. Pandit & Nitin P. Lad

  2. Department of Medicinal Chemistry, Piramal Enterprises Limited 1, Nirlon Complex, Off Western Exp. Highway, Near NSE Complex, Goregaon East, Mumbai, Maharashtra, 400 063, India

    Mahesh R. Kulkarni, Usha Ghosh & Nitin P. Lad

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  1. Shivaji S. Pandit
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Correspondence to Shivaji S. Pandit.

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Pandit, S.S., Kulkarni, M.R., Ghosh, U. et al. Synthesis and biological evaluation of imidazo[1,2-\({{\varvec{b}}}\)]pyridazines as inhibitors of TNF-\({\varvec{\upalpha }}\) production. Mol Divers 22, 545–560 (2018). https://doi.org/10.1007/s11030-017-9798-8

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  • DOI: https://doi.org/10.1007/s11030-017-9798-8

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