High analgesic and anti-inflammatory in vivo activities of six new hybrids NSAIAs tetrahydropyran derivatives.

Autor: Capim SL; Laboratório de Síntese Orgânica Medicinal da Paraíba LASOM-PB, Departamento de Química, Universidade Federal da Paraíba, Campus I, João Pessoa, PB 58059-900, Brazil., Gonçalves GM, Dos Santos GC, Marinho BG, Vasconcellos ML
Jazyk: angličtina
Zdroj: Bioorganic & medicinal chemistry [Bioorg Med Chem] 2013 Oct 01; Vol. 21 (19), pp. 6003-10. Date of Electronic Publication: 2013 Jul 29.
DOI: 10.1016/j.bmc.2013.07.041
Abstrakt: We present in this article syntheses of six new hybrids compounds (4-9) that were efficiently prepared in one or two steps (70-84.6%) from our previous prototype (±)-cis-4-chloro-6-(naphthalen-1-yl)-tetrahydro-2H-pyran-2-yl)methanol (3) and the NSAIAs: acetyl salicylic acid, indomethacin, ibuprofen, ketoprofen, naproxen and diclofenac. The acetic acid-induced writhing method is able to determine that all investigated new hybrids showed stronger antinociceptive properties (2- to 10-fold less ED50 values) than their precursors. The highest antinociceptive effect was observed for compound 9 showing more than 10-fold less ED50 values than diclofenac and ninefold less ED50 value than compound 2. All compounds presented greater activity than the control group in the tail-flick test confirming the central antinociceptive effect. New hybrids did not alter the motor performance of mice by rota-rod performance and open-field tests. Investigated compounds 4-9 were not toxic after oral administration (LD50 >2000mg/kg).
(Copyright © 2013 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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