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Design, synthesis, and evaluation of anti-inflammatory and ulcerogenicity of novel pyridazinone derivatives

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Abstract

A series of pyridazinone-containing compounds were designed and synthesized as congeners for diclofenac, the most potent and widely used NSAID. The target compounds were evaluated for their anti-inflammatory activity on rat paw edema inflammation model against diclofenac as a reference compound. Seven of the tested compounds demonstrated more than 50% inhibition of carrageenan-induced rat paw edema at a dose 10 mg/kg. The compounds, 6-(2-bromophenylamino)pyridazin-3(2H)-one 2a and 6-(2,6-dimethylphenylamino)pyridazin-3(2H)-one 2e, displayed 74 and 73.5% inflammation-inhibitory activity, respectively, which is comparable to diclofenac (78.3%) at the same dose level after 4 h. The most active compounds as anti-inflammatory agents, 2a, 2e, and 6a, displayed fewer number of ulcers and milder ulcer score than indomethacin in ulcerogenicity screening.

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Authors and Affiliations

  1. Pharmaceutical Chemistry Department, Faculty of Pharmacy, Ain Shams University, Cairo, 11566, Egypt

    K. A. M. Abouzid

  2. Organic Chemistry Department, Faculty of Pharmacy, Cairo University, Cairo, Egypt

    N. A. Khalil & E. M. Ahmed

  3. Pharmacology Department, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt

    A. Esmat

  4. Department of Pharmacology, Medical Division, National Research Center, Dokki, Cairo, Egypt

    A. M. Al-Abd

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  1. K. A. M. Abouzid
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  2. N. A. Khalil
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  3. E. M. Ahmed
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  4. A. Esmat
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  5. A. M. Al-Abd
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Correspondence to K. A. M. Abouzid.

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Abouzid, K.A.M., Khalil, N.A., Ahmed, E.M. et al. Design, synthesis, and evaluation of anti-inflammatory and ulcerogenicity of novel pyridazinone derivatives. Med Chem Res 21, 3581–3590 (2012). https://doi.org/10.1007/s00044-011-9895-7

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  • DOI: https://doi.org/10.1007/s00044-011-9895-7

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