Synthesis and pharmacological evaluation of N-phenyl-acetamide sulfonamides designed as novel non-hepatotoxic analgesic candidates.
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.
Barbosa
Maria Letícia de Castro
ML
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.
Melo
Gabriela Muniz de Albuquerque
GM
da Silva
Yolanda Karla Cupertino
YK
Lopes
Raquel de Oliveira
Rde O
de Souza
Everton Tenório
ET
de Queiroz
Aline Cavalcanti
AC
Smaniotto
Salete
S
Alexandre-Moreira
Magna Suzana
MS
Barreiro
Eliezer J
EJ
Lima
Lídia Moreira
LM