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Docking simulations, synthesis, and anti-inflammatory activity evaluation of 2-(N-alkyl)amino-3-nitroimidazo[1,2-a]pyridines

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Abstract

A set of imidazo[1,2-a]pyridine derivatives was submitted to a docking analysis on COX-1 and COX-2. Although most of the compounds showed affinity for both COX-1 and COX-2, compound 1h showed a higher COX-1 affinity while 1i was more selective to COX-2. None of them had ∆G value higher than indomethacin. Compounds 1b, 1c, and 1g were synthesized and evaluated as potential anti-inflammatory agents. Compound 2-(N-cyclopropyl)amino-3-nitroimidazo[1,2-a]pyridine (1c) which gave a very poor affinity for either COX-1 or COX-2, showed anti-inflammatory activity (20 mg/kg) on the cotton pellet granuloma bioassay, with no induction of gastrointestinal damage.

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Acknowledgment

This study was partially supported by the Secretaría de Investigación y de Posgrado, COFAA, (IPN). ICyTDF and CONACYT Grant No. 49937, 62488, 91426.

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Authors and Affiliations

  1. Departamento de Farmacia, Escuela Nacional de Ciencias Biológicas, Campus Zacatenco, Instituto Politécnico Nacional, Av. Wilfrido Massieu s/n Col. Zacatenco, CP 07730, Mexico, DF, Mexico

    Yazmín K. Márquez-Flores & Ma. Estela Meléndez-Camargo

  2. Departamento de Química Orgánica, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Prolongación de Plan de Ayala y Carpio s/n Col. Sto. Tomás, CP 11340, Mexico, DF, Mexico

    Ma. Elena Campos-Aldrete & Héctor Salgado-Zamora

  3. Laboratorio de Modelado Molecular y Bioinformática, SEPI, Escuela Superior de Medicina, Instituto Politécnico Nacional, Plan de San Luis y Díaz Mirón, CP 11340, Mexico, DF, Mexico

    José Correa-Basurto

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  1. Yazmín K. Márquez-Flores
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  2. Ma. Elena Campos-Aldrete
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  3. Héctor Salgado-Zamora
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  4. José Correa-Basurto
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  5. Ma. Estela Meléndez-Camargo
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Correspondence to Ma. Estela Meléndez-Camargo.

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Márquez-Flores, Y.K., Campos-Aldrete, M.E., Salgado-Zamora, H. et al. Docking simulations, synthesis, and anti-inflammatory activity evaluation of 2-(N-alkyl)amino-3-nitroimidazo[1,2-a]pyridines. Med Chem Res 21, 775–782 (2012). https://doi.org/10.1007/s00044-011-9585-5

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  • DOI: https://doi.org/10.1007/s00044-011-9585-5

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