Synthesis and structure-activity relationships of N-substituted spiropiperidines as nociceptin receptor ligands

John P Caldwell; Julius J Matasi; Hongtao Zhang; Ahmad Fawzi; Deen B Tulshian

doi:10.1016/j.bmcl.2007.01.069

Synthesis and structure-activity relationships of N-substituted spiropiperidines as nociceptin receptor ligands

Bioorg Med Chem Lett. 2007 Apr 15;17(8):2281-4. doi: 10.1016/j.bmcl.2007.01.069. Epub 2007 Jan 27.

Authors

John P Caldwell¹, Julius J Matasi, Hongtao Zhang, Ahmad Fawzi, Deen B Tulshian

Affiliation

¹ CV & CNS Department of Chemical Research, Schering Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA. john.caldwell@spcorp.com

PMID: 17289383
DOI: 10.1016/j.bmcl.2007.01.069

Abstract

A series of N-substituted analogs based upon the spiropiperidine core of 1 was synthesized and exhibited high binding affinity to the nociceptin (NOP) receptor. The selectivities against other known opioid receptors were determined.

MeSH terms

Administration, Oral
Animals
Cough / drug therapy
Drug Evaluation, Preclinical
Guanosine 5'-O-(3-Thiotriphosphate)
Ligands
Nociceptin Receptor
Pharmacokinetics
Piperidines / chemical synthesis*
Piperidines / pharmacokinetics
Piperidines / pharmacology
Protein Binding
Rats
Receptors, Opioid / agonists*
Receptors, Opioid / metabolism
Spiro Compounds / chemical synthesis
Spiro Compounds / pharmacokinetics
Spiro Compounds / pharmacology
Structure-Activity Relationship

Substances

Ligands
Piperidines
Receptors, Opioid
Spiro Compounds
Guanosine 5'-O-(3-Thiotriphosphate)
Nociceptin Receptor
Oprl protein, rat