Discovery of N-(2-aryl-cyclohexyl) substituted spiropiperidines as a novel class of GlyT1 inhibitors.
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.
Pinard
Emmanuel
E
F. Hoffmann-La Roche Ltd, Pharmaceutical Research Basel, Discovery Chemistry, CH-4070 Basel, Switzerland. emmanuel.pinard@roche.com
Ceccarelli
Simona M
SM
Stalder
Henri
H
Alberati
Daniela
D
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
D050487:Glycine Plasma Membrane Transport Proteins; D010880:Piperidines; C493268:SLC6A9 protein, human; D013141:Spiro Compounds; C508201:cis-N-(2-phenyl-cyclohexyl)spiropiperidine