Nonpeptide angiotensin II receptor antagonists: N-[(benzyloxy)benzyl]imidazoles and related compounds as potent antihypertensives.
A series of compounds has been synthesized and demonstrated to be antagonists of the angiotensin II (AII) receptor. These compounds are structurally related to the N-(benzamidobenzyl)imidazoles and extend the scope of this new class of nonpeptide AII antagonists. It has been found that the amide linkage (X = NHCO) in the N-(benzamidobenzyl)imidazoles can be replaced successfully by a variety of groups (X = single bond, O, S, CO, OCH2, CH = CH, NHCONH); linkers of 0-1 atoms in length are most effective. When administered intravenously to awake renal hypertensive rats, these compounds are potent antihypertensives.
Carini
D J
DJ
Medicinal Chemistry Section, E. I. du Pont de Nemours and Co., Inc., Wilmington, Delaware 19880.
Duncia
J V
JV
Johnson
A L
AL
Chiu
A T
AT
Price
W A
WA
Wong
P C
PC
Timmermans
P B
PB
D000302:Adrenal Cortex / Q000187:drug effects / Q000378:metabolism; D000804:Angiotensin II / Q000037:antagonists & inhibitors*; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D000959:Antihypertensive Agents / Q000138:chemical synthesis*; D001667:Binding, Competitive; D055598:Chemical Phenomena; D002621:Chemistry; D007093:Imidazoles / Q000138:chemical synthesis* / Q000494:pharmacology; D008861:Microsomes / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D011945:Receptors, Angiotensin / Q000187:drug effects* / Q000378:metabolism; D013329:Structure-Activity Relationship
D057911:Angiotensin Receptor Antagonists; D000959:Antihypertensive Agents; D007093:Imidazoles; D011945:Receptors, Angiotensin; D000804:Angiotensin II