Synthesis and SAR study of 4-arylpiperidines and 4-aryl-1,2,3,6-tetrahydropyridines as 5-HT₂C agonists

Richard J Conway; Celine Valant; Arthur Christopoulos; Alan D Robertson; Ben Capuano; Ian T Crosby

doi:10.1016/j.bmcl.2012.01.122

Synthesis and SAR study of 4-arylpiperidines and 4-aryl-1,2,3,6-tetrahydropyridines as 5-HT₂C agonists

Bioorg Med Chem Lett. 2012 Apr 1;22(7):2560-4. doi: 10.1016/j.bmcl.2012.01.122. Epub 2012 Feb 9.

Authors

Richard J Conway¹, Celine Valant, Arthur Christopoulos, Alan D Robertson, Ben Capuano, Ian T Crosby

Affiliation

¹ Medicinal Chemistry and Drug Action, Monash Institute of Pharmaceutical Science, 381 Royal Parade, Parkville 3052, Australia.

PMID: 22381048
DOI: 10.1016/j.bmcl.2012.01.122

Abstract

A series of substituted 4-arylpiperidines and a smaller family of 4-aryl-1,2,3,6-tetrahydropyridines were synthesized and their biological activity at the 5-HT(2C) receptor studied to determine whether either series showed noteworthy agonist activity. Structure-activity relationships were developed from the performed receptor binding assays and functional studies, and the results of the analysis are presented herein.

MeSH terms

Animals
Appetite Depressants / chemical synthesis*
Appetite Depressants / pharmacology
Calcium / metabolism
Ergolines / pharmacology
Humans
Kinetics
Piperidines / chemical synthesis*
Piperidines / pharmacology
Protein Binding
Pyridines / chemical synthesis*
Pyridines / pharmacology
Radioligand Assay
Receptor, Serotonin, 5-HT2C / chemistry
Receptor, Serotonin, 5-HT2C / metabolism*
Serotonin 5-HT2 Receptor Agonists / chemical synthesis*
Serotonin 5-HT2 Receptor Agonists / pharmacology
Serotonin Antagonists / pharmacology
Stereoisomerism
Structure-Activity Relationship

Substances

Appetite Depressants
Ergolines
Piperidines
Pyridines
Receptor, Serotonin, 5-HT2C
Serotonin 5-HT2 Receptor Agonists
Serotonin Antagonists
mesulergine
Calcium