title: Synthesis of annulated pyridines as inhibitors of aldosterone synthase (CYP11B2).
abstract: A series of cyclopenta[c]pyridine aldosterone synthase (AS) inhibitors were conveniently accessed using batch or continuous flow Kondrat'eva reactions. Preparation of the analogous cyclohexa[c]pyridines led to the identification of a potent and more selective AS inhibitor. The structure-activity-relationship (SAR) in this new series was rationalized using binding mode models in the crystal structure of AS.
authors.affiliation: Medicinal Chemistry, Roche Pharmaceutical Research and Early Development (pRED), Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd, Grenzacherstrasse 124, CH-4070 Basel, Switzerland. rainer_e.martin@roche.com.
authors.forename: Rainer E
authors.initials: RE
authors.lastname: Martin
authors.forename: Johannes
authors.initials: J
authors.lastname: Lehmann
authors.forename: Thibaut
authors.initials: T
authors.lastname: Alzieu
authors.forename: Mario
authors.initials: M
authors.lastname: Lenz
authors.forename: Marjorie A
authors.initials: MA
authors.lastname: Carnero Corrales
authors.forename: Johannes D
authors.initials: JD
authors.lastname: Aebi
authors.forename: Hans Peter
authors.initials: HP
authors.lastname: Märki
authors.forename: Bernd
authors.initials: B
authors.lastname: Kuhn
authors.forename: Kurt
authors.initials: K
authors.lastname: Amrein
authors.forename: Alexander V
authors.initials: AV
authors.lastname: Mayweg
authors.forename: Robert
authors.initials: R
authors.lastname: Britton
mesh_terms: D060326:Chemistry Techniques, Synthetic; D019405:Cytochrome P-450 CYP11B2 / Q000037:antagonists & inhibitors* / Q000737:chemistry; D065607:Cytochrome P-450 Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D008958:Models, Molecular; D011487:Protein Conformation; D011725:Pyridines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D065607:Cytochrome P-450 Enzyme Inhibitors; D011725:Pyridines; D019405:Cytochrome P-450 CYP11B2