title: Design and optimization of new piperidines as renin inhibitors.
abstract: The discovery of a new series of piperidine-based renin inhibitors is described herein. SAR optimization upon the P3 renin sub-pocket is described, leading to the discovery of 9 and 41, two bioavailable renin inhibitors orally active at low doses in a transgenic rat model of hypertension.
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: Corinna
authors.initials: C
authors.lastname: Grisostomi
authors.forename: Luboš
authors.initials: L
authors.lastname: Remeň
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: Patrick
authors.initials: P
authors.lastname: Hess
authors.forename: Panja
authors.initials: P
authors.lastname: Strickner
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: D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D051544:Cytochrome P-450 CYP3A; D065607:Cytochrome P-450 Enzyme Inhibitors; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D008958:Models, Molecular; D010880:Piperidines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D011487:Protein Conformation; D051381:Rats; D013329:Structure-Activity Relationship; D014961:X-Ray Diffraction; D000092502:Renin Inhibitors
chemical_list: D000959:Antihypertensive Agents; D051544:Cytochrome P-450 CYP3A; D065607:Cytochrome P-450 Enzyme Inhibitors; D004791:Enzyme Inhibitors; D010880:Piperidines; D000092502:Renin Inhibitors; C465260:Cyp3a2 protein, rat