title: Discovery of N-(2-aryl-cyclohexyl) substituted spiropiperidines as a novel class of GlyT1 inhibitors.
abstract: Screening of the Roche compound library led to the identification of cis-N-(2-phenyl-cyclohexyl)-spiropiperidine 1 as structurally novel GlyT1 inhibitor. The SAR, which was developed in this series, resulted in the discovery of highly potent compounds displaying excellent selectivity against the GlyT2 isoform.
authors.affiliation: F. Hoffmann-La Roche Ltd, Pharmaceutical Research Basel, Discovery Chemistry, CH-4070 Basel, Switzerland. emmanuel.pinard@roche.com
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Pinard
authors.forename: Simona M
authors.initials: SM
authors.lastname: Ceccarelli
authors.forename: Henri
authors.initials: H
authors.lastname: Stalder
authors.forename: Daniela
authors.initials: D
authors.lastname: Alberati
mesh_terms: D004353:Drug Evaluation, Preclinical; D050487:Glycine Plasma Membrane Transport Proteins / Q000037:antagonists & inhibitors*; D006801:Humans; D008968:Molecular Conformation; D010880:Piperidines / Q000737:chemistry / Q000145:classification / Q000494:pharmacology; D013141:Spiro Compounds / Q000737:chemistry / Q000145:classification / Q000494:pharmacology; D013329:Structure-Activity Relationship
chemical_list: D050487:Glycine Plasma Membrane Transport Proteins; D010880:Piperidines; C493268:SLC6A9 protein, human; D013141:Spiro Compounds; C508201:cis-N-(2-phenyl-cyclohexyl)spiropiperidine