Discovery of 4-substituted-8-(2-hydroxy-2-phenyl-cyclohexyl)-2,8-diaza-spiro[4.5]decan-1-one as a novel class of highly selective GlyT1 inhibitors with improved metabolic stability

Bioorganic and Medicinal Chemistry Letters

Volumn 16, Issue 16, 2006, Pages 4311-4315

  Alberati, Daniela ^a   Hainzl, Dominik ^a   Jolidon, Synèse ^a   Krafft, Eva A ^a   Kurt, Anke ^a   Maier, Axel ^a   Pinard, Emmanuel ^a   Thomas, Andrew W ^a   Zimmerli, Daniel ^a  

^a F HOFFMANN LA ROCHE LTD   (Switzerland)

Author keywords

Glycine; GlyT1; GlyT2; NMDA; Schizophrenia; Spiropiperidine; Transporter

Indexed keywords

GLYCINE TRANSPORTER 1 INHIBITOR; MU OPIATE RECEPTOR; NITROGEN DERIVATIVE; NOCICEPTIN; NOCICEPTIN RECEPTOR; PIPERIDINE DERIVATIVE; POTASSIUM CHANNEL HERG; PROTEIN INHIBITOR; UNCLASSIFIED DRUG;

ARTICLE; BINDING AFFINITY; COMPARATIVE STUDY; DRUG ACTIVITY; DRUG IDENTIFICATION; DRUG MECHANISM; DRUG METABOLISM; DRUG POTENCY; DRUG SELECTIVITY; DRUG STABILITY; NONHUMAN; RODENT; SUBSTITUTION REACTION;

ANIMALS; CHEMISTRY, PHARMACEUTICAL; DRUG DESIGN; ETHER-A-GO-GO POTASSIUM CHANNELS; GLYCINE PLASMA MEMBRANE TRANSPORT PROTEINS; HUMANS; INHIBITORY CONCENTRATION 50; KINETICS; MICE; MICROSOMES; MODELS, CHEMICAL; OPIOID PEPTIDES; PEPTIDES; PROTEIN ISOFORMS; RECEPTORS, OPIOID;

RODENTIA;

EID: 33745699199     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2006.05.058     Document Type: Article

References (17)

1. Eulenburg V., Armsen W., Betz H., and Gomeza J. Trends Biochem. Sci. 30 (2005) 325
2. Gomeza J., Ohno K., and Betz H. Curr. Opin. Drug Discov. Devel. 6 (2003) 675
3. Danysz W., and Parsons C.G. Pharmacol. Rev. 50 (1998) 597
4. Bergeron R., Meyer T.M., Coyle J.T., and Greene R.W. Proc. Natl. Acad. Sci. U.S.A. 95 (1998) 15730
5. For a recent review, see:. Millan M.J. Psychopharmacology 179 (2005) 30
6. Tsai G., Lane H.-Y., Yang P., Chong M.-Y., and Lange N. Biol. Psychiatry 55 (2004) 452
7. For recent reviews, see:. Sur C., and Kinney G.G. Expert Opin. Investig. Drugs 13 (2004) 515
8. Slassi A., and Egle I. Expert Opin. Ther. Patents 14 (2004) 201
9. Hashimoto K. Recent Pat. CNS Drug Disc. 1 (2006) 43
10. Ceccarelli, S. M.; Pinard, E.; Stalder, H. WO Patent 2005040166, 2005; Chem. Abstr. 2005, 142, 447121.
11. Pinard E., Ceccarelli S.M., Stalder H., and Alberati D. Bioorg. Med. Chem. Lett. 16 (2006) 349
12. Ceccarelli S.M., Pinard E., Stalder H., and Alberati D. Bioorg. Med. Chem. Lett. 16 (2006) 354
13. Alberati D., Ceccarelli S.M., Jolidon S., Krafft E.A., Kurt A., Maier A., Pinard E., Stalder H., Studer D., Thomas A.W., and Zimmerli D. Bioorg. Med. Chem. Lett. 16 (2006) preceding paper
14. Alberati, D.; Ceccarelli, S. M.; Jolidon, S.; Pinard, E.; Thomas, A. W. US Patent 2005154001, 2005; Chem. Abstr. 2005, 143, 115462.
15. Krafft E.A., Kurt A., Maier A., Thomas A.W., and Zimmerli D. Synthesis (2005) 3245
16. Wichmann J., Adam G., Roever S., Hennig M., Scalone M., Cesura A.M., and Dautzenberg F.M. Eur. J. Med. Chem. 35 (2000) 839
17. Berti G., Catelani G., Ferretti M., and Monti L. Tetrahedron 30 (1974) 4013