2 research outputs found
Novel bronchodilators: Synthesis, transamination reactions, and pharmacology of a series of pyrazino[2,3-c][1,2,6]thiadiazine 2,2-dioxides
The synthesis, pharmacological evaluation, and structure-activity relationships of a new class
of bronchodilator agents, derivatives of pyrazino[2,3-c][1,2,6]thiadiazine 2,2-dioxides are
described. The compounds were prepared by reaction of 3,4,5-triamino-1,2,6-thiadiazine 1,1-
dioxide with suitable 1,2-dicarbonyl compounds or R-hydroxyiminoketones and subsequent
N-alkylation. A transamination procedure for synthesizing derivatives with different substituents
at the 4-amino group is reported for the first time. The pyrazino[2,3-c][1,2,6]thiadiazine
derivatives were screened for tracheal relaxing activity in vitro, and the active compounds
were evaluated in vivo in guinea pigs as bronchodilator agents in comparison to theophylline.
Among the compounds studied, the most interesting properties were displayed by the 4-amino-
1-ethyl-6-methyl derivative (21). The toxicological evaluation of this derivative is also reported.We are grateful to E. Carrasco
and M. Grau from Prodesfarma S. A., Barcelona, Spain,
for biological assaysPeer reviewe