Angiotensin-converting enzyme inhibitors. 9. Novel [[N-(1-carboxy-3-phenylpropyl)amino]acyl]glycine derivatives with diuretic activity.
A series of molecules 1 having sulfonamide diuretic moieties covalently linked to non-sulfhydryl angiotensin-converting enzyme inhibitors (ACEI) were prepared and tested for both activities. IC50 values for ACEI as low as 7 nM were observed. Discernable diuretic activity was seen for several hydrochlorothiazide-based molecules. Effects of the ACEI and diuretic structures on the respective potencies are discussed.
Barton
J N
JN
Rorer Central Research, King of Prussia, Pennsylvania 19406.
Piwinski
J J
JJ
Skiles
J W
JW
Regan
J R
JR
Menard
P R
PR
Desai
R
R
Golec
F S
FS
Reilly
L W
LW
Goetzen
T
T
Ueng
S N
SN
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000138:chemical synthesis; D000818:Animals; D004232:Diuretics / Q000138:chemical synthesis; D015195:Drug Design; D005998:Glycine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D008297:Male; D011437:Propylamines / Q000138:chemical synthesis / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR
D000806:Angiotensin-Converting Enzyme Inhibitors; D004232:Diuretics; D011437:Propylamines; D005998:Glycine