Dibenzoquinazoline diones as antihypertensive cyclic guanosine monophosphate phosphodiesterase inhibitors.
The discovery and structure-activity of a new class of renal artery phosphodiesterase inhibitors is reported, some of which are highly selective for the guanosine cyclic 3',5'-monophosphate phosphodiesterase. One of these compounds, 5,6-dihydro-8,9,11,12-tetramethoxy-1,3-dioxo-1H-benz[f]- isoquino [8,1,2- hij]quinazoline-2(3H)-carboxylic acid, ethyl ester (9), is amongst the most potent and selective compounds of this class yet identified. Furthermore, this compound demonstrates an antihypertensive effect in vivo which is presumably mediated through vascular smooth muscle relaxation.
Booth
R F
RF
Department of Biology, Searle & Co. Ltd., High Wycombe, Buckinghamshire, U.K.
Buckham
S P
SP
Lunt
D O
DO
Manley
P W
PW
Porter
R A
RA
D015106:3',5'-Cyclic-GMP Phosphodiesterases / Q000037:antagonists & inhibitors*; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D002417:Cattle; D007546:Isoquinolines / Q000494:pharmacology*; D051381:Rats; D011918:Rats, Inbred SHR; D013329:Structure-Activity Relationship; D044005:Tetrahydroisoquinolines
D000959:Antihypertensive Agents; D007546:Isoquinolines; D044005:Tetrahydroisoquinolines; C035964:trequinsin; D015106:3',5'-Cyclic-GMP Phosphodiesterases