Discovery of N-(2-aryl-cyclohexyl) substituted spiropiperidines as a novel class of GlyT1 inhibitors

Emmanuel Pinard; Simona M Ceccarelli; Henri Stalder; Daniela Alberati

doi:10.1016/j.bmcl.2005.09.075

Discovery of N-(2-aryl-cyclohexyl) substituted spiropiperidines as a novel class of GlyT1 inhibitors

Bioorg Med Chem Lett. 2006 Jan 15;16(2):349-53. doi: 10.1016/j.bmcl.2005.09.075. Epub 2005 Oct 21.

Authors

Emmanuel Pinard¹, Simona M Ceccarelli, Henri Stalder, Daniela Alberati

Affiliation

¹ F. Hoffmann-La Roche Ltd, Pharmaceutical Research Basel, Discovery Chemistry, CH-4070 Basel, Switzerland. emmanuel.pinard@roche.com

PMID: 16246557
DOI: 10.1016/j.bmcl.2005.09.075

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.

MeSH terms

Drug Evaluation, Preclinical
Glycine Plasma Membrane Transport Proteins / antagonists & inhibitors*
Humans
Molecular Conformation
Piperidines* / chemistry
Piperidines* / classification
Piperidines* / pharmacology
Spiro Compounds* / chemistry
Spiro Compounds* / classification
Spiro Compounds* / pharmacology
Structure-Activity Relationship

Substances

Glycine Plasma Membrane Transport Proteins
Piperidines
SLC6A9 protein, human
Spiro Compounds
cis-N-(2-phenyl-cyclohexyl)spiropiperidine