Synthesis and pharmacological evaluation of pyrazine N-acylhydrazone derivatives designed as novel analgesic and anti-inflammatory drug candidates.
In this paper, we report the synthesis and pharmacological evaluation of pyrazine N-acylhydrazone (NAH) derivatives (2a-s) designed as novel analgesic and anti-inflammatory drug candidates. This series was planned by molecular simplification of prototype 1 (LASSBio-1018), previously described as a non-selective cyclooxygenase inhibitor. Derivatives 2a-s were evaluated in several animal models of pain and inflammation, standing-out compound 2o (2-N'-[(E)-(3,4,5-trimethoxyphenyl) methylidene]-2-pyrazinecarbohydrazide; LASSBio-1181), that was also active in a murine model of chronic inflammation (i.e., adjuvant-induced arthritis test in rats) and can be considered a new analgesic and anti-inflammatory lead for drug development.
da Silva
Yolanda Karla Cupertino
YK
LaFI-Laboratório de Farmacologia e Imunidade, Instituto de Ciências Biológicas e da Saúde, Universidade Federal de Alagoas, Maceió, AL, Brazil.
Augusto
Cristina Villarinho
CV
de Castro Barbosa
Maria Letícia
ML
de Albuquerque Melo
Gabriela Muniz
GM
de Queiroz
Aline Cavalcanti
AC
de Lima Matos Freire Dias
Thays
T
Júnior
Walfrido Bispo
WB
Barreiro
Eliezer J
EJ
Lima
Lídia Moreira
LM
Alexandre-Moreira
Magna Suzana
MS
D000700:Analgesics / Q000138:chemical synthesis / Q000737:chemistry* / Q000627:therapeutic use*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000627:therapeutic use*; D001168:Arthritis / Q000139:chemically induced / Q000188:drug therapy*; D004423:Ear / Q000473:pathology; D004487:Edema / Q000139:chemically induced / Q000188:drug therapy; D005260:Female; D005620:Freund's Adjuvant; D006835:Hydrazones / Q000138:chemical synthesis / Q000737:chemistry* / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D010146:Pain / Q000188:drug therapy*; D010538:Peritonitis / Q000139:chemically induced / Q000188:drug therapy; D011719:Pyrazines / Q000138:chemical synthesis / Q000737:chemistry* / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D015054:Zymosan
D000700:Analgesics; D000893:Anti-Inflammatory Agents; D006835:Hydrazones; D011719:Pyrazines; D005620:Freund's Adjuvant; D015054:Zymosan