title: Piperidine-based renin inhibitors: upper chain optimization.
abstract: 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.
authors.affiliation: Drug Discovery Chemistry & Biochemistry, Actelion Pharmaceuticals Ltd, Gewerbestrasse 16, 4123 Allschwil, Switzerland.
authors.forename: Olivier
authors.initials: O
authors.lastname: Corminboeuf
authors.forename: Olivier
authors.initials: O
authors.lastname: Bezençon
authors.forename: Luboš
authors.initials: L
authors.lastname: Remeň
authors.forename: Corinna
authors.initials: C
authors.lastname: Grisostomi
authors.forename: Sylvia
authors.initials: S
authors.lastname: Richard-Bildstein
authors.forename: Daniel
authors.initials: D
authors.lastname: Bur
authors.forename: Lars
authors.initials: L
authors.lastname: Prade
authors.forename: Panja
authors.initials: P
authors.lastname: Strickner
authors.forename: Patrick
authors.initials: P
authors.lastname: Hess
authors.forename: Walter
authors.initials: W
authors.lastname: Fischli
authors.forename: Beat
authors.initials: B
authors.lastname: Steiner
authors.forename: Alexander
authors.initials: A
authors.lastname: Treiber
mesh_terms: 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
chemical_list: 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