title: Design, synthesis, antinociceptive and anti-inflammatory activities of novel piroxicam analogues.
abstract: In this paper we report the design, synthesis, antinociceptive and anti-inflammatory activities of a series of benzothiazine N-acylhydrazones 14a–h, planned by structural modification of piroxicam (1), a non steroidal anti-inflammatory drug. Among the synthesized analogues, compounds 14f (LASSBio-1637) and 14g (LASSBio-1639) were identified as novel antinociceptive and anti-inflammatory prototypes, active by oral administration, acting by a mechanism of action that seems to be different from that of piroxicam, since they were inactive as an inhibitor of cyclooxygenase (COX-1 and COX-2) at concentrations of 10 mM.
authors.affiliation: Bio - Laboratório de Avaliação e Síntese de Substâncias Bioativas, Faculdade de Farmácia, Universidade Federal do Rio de Janeiro, P.O. Box 68024, 21944-971 Rio de Janeiro, RJ, Brazil.
authors.forename: Amanda Silva
authors.initials: AS
authors.lastname: de Miranda
authors.forename: Walfrido
authors.initials: W
authors.lastname: Bispo Júnior
authors.forename: Yolanda Karla Cupertino
authors.initials: YK
authors.lastname: da Silva
authors.forename: Magna Suzana
authors.initials: MS
authors.lastname: Alexandre-Moreira
authors.forename: Rosane de Paula
authors.initials: Rde P
authors.lastname: Castro
authors.forename: José Ricardo
authors.initials: JR
authors.lastname: Sabino
authors.forename: Luciano Morais
authors.initials: LM
authors.lastname: Lião
authors.forename: Lídia Moreira
authors.initials: LM
authors.lastname: Lima
authors.forename: Eliezer J
authors.initials: EJ
authors.lastname: Barreiro
mesh_terms: D000284:Administration, Oral; D000700:Analgesics / Q000138:chemical synthesis / Q000494:pharmacology; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000138:chemical synthesis / Q000494:pharmacology; D001581:Benzothiadiazines / Q000138:chemical synthesis / Q000494:pharmacology; D051545:Cyclooxygenase 1 / Q000737:chemistry; D051546:Cyclooxygenase 2 / Q000737:chemistry; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D008565:Membrane Proteins / Q000737:chemistry; D051379:Mice; D015394:Molecular Structure; D010894:Piroxicam / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000700:Analgesics; D000893:Anti-Inflammatory Agents; D001581:Benzothiadiazines; D016861:Cyclooxygenase Inhibitors; D008565:Membrane Proteins; D010894:Piroxicam; C077623:Ptgs2 protein, mouse; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496512:Ptgs1 protein, mouse