N-substituted pyrazino[2,3-c][1,2,6]thiadiazine 2,2-dioxides. A new class of diuretics.
The synthesis and evaluation of a new class of diuretic agents derived from the pyrazino[2,3-c][1,2,6]thiadiazine 2,2-dioxide ring system are described. Preliminary structure-activity relationships indicate that the nature and location of the substituents at different positions of the heterocycle are crucial for activity. Thus, a novel synthetic methodology has been developed to selectively introduce the desired substituents at different positions. From the study of the pharmacological properties (dose-response curves, duration of action, and acute toxicity) of the most active compounds, 4-amino-1,7-diethyl-6-methylpyrazino[2,3-c][1,2,6]thiadiazine++ + 2,2-dioxide (9) was selected for further investigation. Compound 9 (C10H15N5O2S) crystallizes in space group P21/a with unit cell dimensions a = 16.482 (1), b = 9.3484 (3), c = 8.333 (3) A, beta = 103.003 (3) degrees, Z = 4.
Goya
P
P
Instituto de Química Médica (C.S.I.C.), Madrid, Spain.
Paez
J A
JA
Alkorta
I
I
Carrasco
E
E
Grau
M
M
Anton
F
F
Julia
S
S
Martinez-Ripoll
M
M
D000818:Animals; D004232:Diuretics / Q000138:chemical synthesis* / Q000494:pharmacology; D008297:Male; D051379:Mice; D008958:Models, Molecular; D015394:Molecular Structure; D009318:Natriuresis / Q000187:drug effects; D011719:Pyrazines / Q000138:chemical synthesis / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013329:Structure-Activity Relationship; D013829:Thiadiazines / Q000138:chemical synthesis* / Q000494:pharmacology; D014961:X-Ray Diffraction
D004232:Diuretics; D011719:Pyrazines; D013829:Thiadiazines