Renin inhibitors: C-terminal oxetanes as potent transition-state mimics.
A novel transition-state mimic containing a C-terminal oxetane has been developed. Renin inhibitors incorporating this fragment exhibit enhanced potency against human plasma renin at physiological pH. The binding affinity of this new species has allowed size reductions at other sites.
Rosenberg
S H
SH
Pharmaceutical Products Division, Abbott Laboratories, Abbott Park, IL 60064.
Spina
K P
KP
Stein
H
H
Cohen
J
J
Baker
W R
WR
Kleinert
H D
HD
D004151:Dipeptides / Q000138:chemical synthesis* / Q000494:pharmacology*; D004988:Ethers, Cyclic / Q000138:chemical synthesis* / Q000494:pharmacology*; D005663:Furans / Q000138:chemical synthesis* / Q000494:pharmacology*; D006801:Humans; D012083:Renin / Q000097:blood; D013329:Structure-Activity Relationship; D000092502:Renin Inhibitors
D004151:Dipeptides; D004988:Ethers, Cyclic; D005663:Furans; D012083:Renin; D000092502:Renin Inhibitors; C018674:tetrahydrofuran