Slow, tight binding to human renin of some nonpeptidic renin inhibitors containing a 4-methoxymethoxypiperidinylamide at the P4 position.
A series of nonpeptidic human renin inhibitors with a 4-methoxymethoxypiperidinylamide at the P4 position of the molecule exhibited slow tight binding to the enzyme. Replacement of the methoxymethoxy moiety on the piperidine ring with H, OH, methoxyethyl, propyloxy or n-butyl eliminated the effect. The inhibition was partially reversed by prolonged dialysis at 4 degrees C, arguing against formation of a covalent bond in the tightened complex.
Stein
H H
HH
Abbott Laboratories, Cardiovascular Research Division, Abbott Park, Illinois 60064.
Fung
A K
AK
Cohen
J
J
Baker
W R
WR
Rosenberg
S H
SH
Boyd
S A
SA
Dayton
B D
BD
Armiger
Y L
YL
Condon
S L
SL
Mantei
R A
RA
D001665:Binding Sites; D004789:Enzyme Activation; D006801:Humans; D010880:Piperidines / Q000737:chemistry*; D011485:Protein Binding; D012083:Renin / Q000097:blood / Q000737:chemistry; D013329:Structure-Activity Relationship; D000092502:Renin Inhibitors
D010880:Piperidines; D012083:Renin; D000092502:Renin Inhibitors; C032727:piperidine