Synthesis, X-ray diffraction study and pharmacological evaluation of 3-amino-4-methylthiophene-2-acylcarbohydrazones

• Main Authors: SONJA HERRMANN, TABEA SCHÜBEL, FANNY N. COSTA, MARIA LETÍCIA C. BARBOSA, FABIO F. FERREIRA, THAYS L.M.F. DIAS, MORGANA V. ARAÚJO, MAGNA S. ALEXANDRE-MOREIRA, LÍDIA M. LIMA, STEFAN LAUFER, ELIEZER J. BARREIRO
• Format: Article
• Language: English
• Published: Academia Brasileira de Ciências
• Series: Anais da Academia Brasileira de Ciências
• Subjects: N-acylhydrazone; privileged structure; antinociceptive; p38MAPK; X-ray
• Online Access: http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0001-37652018000301073&lng=en&tlng=en

ABSTRACT N-acylhydrazone is an interesting privileged structure that has been used in the molecular design of a myriad of bioactive compounds. In order to identify new antinociceptive drug candidates, we described herein the design, synthesis, X-ray diffraction study and the pharmacological evaluation of a series of 3-amino-4-methylthiophene-2-acylcarbohydrazone derivatives (8a-t). Compounds were prepared in good overall yields through divergent synthesis from a common key intermediate and were characterized by classical spectroscopy methods. X-ray diffraction study was employed for unequivocal determination of the imine double bond stereochemistry. 8a-t were evaluated in vivo through oral administration using the classical writhing test in mice. N-acylhydrazone derivatives 8j and 8l displayed relative potency similar to dipyrone, highlighting them as promising analgesic lead-candidates for further investigation.