Derivatives of 1,2-diazetidine-1,2-di-N-oxides--a new class of soluble guanylate cyclase activators with vasodilatory properties.
Derivatives of diazetidine-di-N-oxides have been found capable of the nonenzymatic generation of nitric oxide by the principally new mechanism of the nitric oxide splitting at physiological pH values. The effect of the synthesized compounds on human platelet soluble guanylate cyclase activity as well as their spasmolytic and hypotensive action were studied. Four of 7 derivatives studied exhibited a distinct correlation between the ability of being decomposed with the nitric oxide formation, activation of soluble guanylate cyclase, and spasmolytic and antihypertensive activities. Among them, 3-brom, 4-methyl-3,4-tetramethylene-diazetidine-di-N-oxide has proved to be most effective, its spasmolytic effect being commensurable with glyceryl trinittrate activity. The revealed correlation allows us to regard 1,2-diazetidine-1,2-di-N-oxide derivatives as vasodilatory agents of a new class.
Severina
I S
IS
Institute of Biomedical Chemistry, Russian Academy of Medical Sciences, Moscow.
Ryaposova
I K
IK
Volodarsky
L B
LB
Mozhuchin
D C
DC
Tichonov AYa
Schwartz GYa
Granik
V G
VG
Grigoryev
D A
DA
Grigoryev
N B
NB
D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001384:Azetidines / Q000494:pharmacology*; D001792:Blood Platelets / Q000201:enzymology*; D001794:Blood Pressure / Q000187:drug effects*; D004789:Enzyme Activation; D006162:Guanylate Cyclase / Q000097:blood / Q000378:metabolism*; D006801:Humans; D015394:Molecular Structure; D010087:Oxides / Q000494:pharmacology*; D051381:Rats; D011918:Rats, Inbred SHR; D013329:Structure-Activity Relationship; D014665:Vasodilator Agents / Q000494:pharmacology*
D000959:Antihypertensive Agents; D001384:Azetidines; D010087:Oxides; D014665:Vasodilator Agents; D006162:Guanylate Cyclase