Renin inhibitors containing isosteric replacements of the amide bond connecting the P3 and P2 sites.
Renin inhibitors having 13 different isosteres connecting the P3 and P2 positions have been prepared. Synthetic routes and in vitro activity exhibited by these compounds are discussed. The two most potent compounds, 47 and 48, contained the hydroxyethylene isostere, psi [CHOHCH2], and had IC50 values of 61 and 22 nM, respectively.
Department of Chemistry, Warner-Lambert Company, Ann Arbor, Michigan 48105.
J S
JS
Kaltenbronn
J P
JP
Hudspeth
E A
EA
Lunney
B M
BM
Michniewicz
E D
ED
Nicolaides
J T
JT
Repine
W H
WH
RoarK
M A
MA
Stier
F J
FJ
Tinney
P K
PK
Woo
D000959:Antihypertensive Agents / Q000138:chemical synthesis; D055598:Chemical Phenomena; D002621:Chemistry; D002918:Chymotrypsin / Q000378:metabolism; D006801:Humans; D006868:Hydrolysis; D066298:In Vitro Techniques; D011480:Protease Inhibitors / Q000138:chemical synthesis* / Q000378:metabolism; D013329:Structure-Activity Relationship; D000092502:Renin Inhibitors
D000959:Antihypertensive Agents; D002918:Chymotrypsin; D011480:Protease Inhibitors; D000092502:Renin Inhibitors