title: High analgesic and anti-inflammatory in vivo activities of six new hybrids NSAIAs tetrahydropyran derivatives.
abstract: 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).
authors: Laboratório de Síntese Orgânica Medicinal da Paraíba LASOM-PB, Departamento de Química, Universidade Federal da Paraíba, Campus I, João Pessoa, PB 58059-900, Brazil.
authors: Saulo L
authors: SL
authors: Capim
authors: Gabriela M
authors: GM
authors: Gonçalves
authors: Gabriela C M
authors: GC
authors: Dos Santos
authors: Bruno G
authors: BG
authors: Marinho
authors: Mário L A A
authors: ML
authors: Vasconcellos
mesh_terms: D000700:Analgesics / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D004008:Diclofenac / Q000737:chemistry / Q000494:pharmacology; D051379:Mice; D015394:Molecular Structure; D009043:Motor Activity / Q000187:drug effects; D011714:Pyrans / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000700:Analgesics; D000893:Anti-Inflammatory Agents; D000894:Anti-Inflammatory Agents, Non-Steroidal; D011714:Pyrans; D004008:Diclofenac
keywords: Antinociceptive; Hybridization; In vivo; NSAIAs; Tetrahydropyran