Antihypertensive thiadiazoles. 2. Vasodilator activity of some 2-aryl-5-guanidino-1,3,4-thiadiazoles.
Some 2-aryl-5-guanidino-(or N-substituted guanidino)-1,3,4-thiadiazoles and closely related analogues were found to lower blood pressure in metacorticoid (DOCA) hypertensive rats. In the unsubstituted guanidines that exhibited low toxicity, optimum activity resulted when the aryl group was a 2-methylphenyl ring (11). Modifications to the guanidine group did not increase antihypertensive activity, but, in the 2-methylphenyl series, the N-n-butyl- and N-(2-methoxyethyl)guanidines (63 and 78) and the related iminoimidazolidine 93 were of comparable activity to that of the unsubstituted guanidine 11. The iminoimidazolidine 93 showed a somewhat longer duration of action than the guanidine derivatives. Preliminary studies in a pithed rat preparation indicated that these thiadiazole derivatives (11, 63, and 93) lowered blood pressure by a direct relaxant effect on vascular smooth muscle.
Turner
S
S
Department of Medicinal Chemistry, Reckitt and Colman plc, Kingston-upon-Hull, United Kingdom.
Myers
M
M
Gadie
B
B
Hale
S A
SA
Horsley
A
A
Nelson
A J
AJ
Pape
R
R
Saville
J F
JF
Doxey
J C
JC
Berridge
T L
TL
D000818:Animals; D000959:Antihypertensive Agents / Q000138:chemical synthesis*; D001794:Blood Pressure / Q000187:drug effects*; D055598:Chemical Phenomena; D002621:Chemistry; D003655:Decerebrate State; D006146:Guanidines / Q000138:chemical synthesis / Q000494:pharmacology*; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D051381:Rats; D013329:Structure-Activity Relationship; D013830:Thiadiazoles / Q000138:chemical synthesis / Q000494:pharmacology*
D000959:Antihypertensive Agents; D006146:Guanidines; D013830:Thiadiazoles