title: Synthesis and pharmacological evaluation of N-phenyl-acetamide sulfonamides designed as novel non-hepatotoxic analgesic candidates.
abstract: In this paper we report the design, synthesis and pharmacological evaluation of a series of N-phenyl-acetamide sulfonamide derivatives (5a-g), planned by structural modification on the prototype paracetamol (1). In this series (5a-g), compound LASSBio-1300 (5e; ID(50)=5.81 micromol/kg) stands out as a new non-hepatotoxic analgesic drug candidate. The increase of area, volume and electrostatic potential of paracetamol's analogues seems to be beneficial to the analgesic activity. Unlike paracetamol (1) and the other analogues (5a, 5d-g), compounds 5b and 5c presented an important anti-hypernociceptive activity associated to inflammatory pain.
authors.affiliation: 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: Maria Letícia de Castro
authors.initials: ML
authors.lastname: Barbosa
authors.forename: Gabriela Muniz de Albuquerque
authors.initials: GM
authors.lastname: Melo
authors.forename: Yolanda Karla Cupertino
authors.initials: YK
authors.lastname: da Silva
authors.forename: Raquel de Oliveira
authors.initials: Rde O
authors.lastname: Lopes
authors.forename: Everton Tenório
authors.initials: ET
authors.lastname: de Souza
authors.forename: Aline Cavalcanti
authors.initials: AC
authors.lastname: de Queiroz
authors.forename: Salete
authors.initials: S
authors.lastname: Smaniotto
authors.forename: Magna Suzana
authors.initials: MS
authors.lastname: Alexandre-Moreira
authors.forename: Eliezer J
authors.initials: EJ
authors.lastname: Barreiro
authors.forename: Lídia Moreira
authors.initials: LM
authors.lastname: Lima