Piperidine-based renin inhibitors: upper chain optimization.
The optimization of the 4-position of recently described new 3,4-disubstituted piperidine-based renin inhibitors is reported herein. The synthesis and characterization of compounds leading to the discovery of 11 (ACT-178882, MK-1597), a renin inhibitor with a suitable profile for development is described.
Corminboeuf
Olivier
O
Drug Discovery Chemistry & Biochemistry, Actelion Pharmaceuticals Ltd, Gewerbestrasse 16, 4123 Allschwil, Switzerland.
Bezençon
Olivier
O
Remeň
Luboš
L
Grisostomi
Corinna
C
Richard-Bildstein
Sylvia
S
Bur
Daniel
D
Prade
Lars
L
Strickner
Panja
P
Hess
Patrick
P
Fischli
Walter
W
Steiner
Beat
B
Treiber
Alexander
A
D000808:Angiotensinogen / Q000235:genetics; D000818:Animals; D030801:Animals, Genetically Modified; D051544:Cytochrome P-450 CYP3A; D065607:Cytochrome P-450 Enzyme Inhibitors; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D007202:Indicators and Reagents; D008958:Models, Molecular; D010880:Piperidines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D012083:Renin / Q000235:genetics; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D000092502:Renin Inhibitors
D000808:Angiotensinogen; D051544:Cytochrome P-450 CYP3A; D065607:Cytochrome P-450 Enzyme Inhibitors; D004791:Enzyme Inhibitors; D007202:Indicators and Reagents; D010880:Piperidines; D012083:Renin; D000092502:Renin Inhibitors; C465260:Cyp3a2 protein, rat