[(6,7-Dichlorobenzo[b]thien-5-yl)oxy]acetic acids and 1,1-dioxides. 1. A structurally novel class of diuretics with hypotensive activity.
A series of [(6,7-dichlorobenzo[b]thien-5-yl)oxy]acetic acids and their corresponding 1,1-dioxides were synthesized and evaluated for diuretic activity in the acute saline loaded mice (ASLM) and hypotensive activity in the spontaneously hypertensive rat (SHR). A significant number of compounds were found to display potent activity in one or both assays, and preliminary structure-activity relationships with respect to each assay were delineated. Compound 94, the 1,1-dioxide of [(6,7-dichloro-2-n-propylbenzo[b]thien-5-yl)oxy]acetic acid was markedly active in both the ASLM and SHR by oral administration. The combined diuretic/hypotensive profile of this compound was further substantiated by its good saluretic response in water loaded conscious dogs and a moderate to good activity in renal hypertensive rats and sinoaortic-deafferented hypertensive dogs.
Ong
H H
HH
Department of Chemical Research, Hoechst-Roussel Pharmaceuticals, Inc., Somerville, New Jersey 08876.
Caldwell
S R
SR
Profitt
J A
JA
Tegeler
J J
JJ
Agnew
M N
MN
Wilker
J C
JC
Ress
R J
RJ
Kitzen
J M
JM
D000085:Acetates / Q000138:chemical synthesis / Q000494:pharmacology; D000818:Animals; D000959:Antihypertensive Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D004232:Diuretics / Q000138:chemical synthesis* / Q000494:pharmacology; D004285:Dogs; D005260:Female; D006016:Glycolates / Q000138:chemical synthesis* / Q000494:pharmacology; D008297:Male; D051379:Mice; D051381:Rats; D011918:Rats, Inbred SHR; D011919:Rats, Inbred Strains; D013329:Structure-Activity Relationship; D013876:Thiophenes / Q000138:chemical synthesis* / Q000494:pharmacology
D000085:Acetates; D000959:Antihypertensive Agents; D004232:Diuretics; D006016:Glycolates; D013876:Thiophenes