Is a nitrogen atom an important pharmacophoric element in sigma ligand binding?
A lingering question in sigma receptor ligand development is whether a nitrogen atom serves as an important pharmacophoric element in binding affinity. To address this question, we have synthesized several phenylalkylpiperidines and phenylalkylpiperazines and demonstrated that removal of the N atom from a typical phenylalkylpiperidine led to little or no binding to sigma receptors. In addition, where two N atoms occur in a compound, such as with phenylalkylpiperazines, the N atom on the longer alkyl chain appears to be more important. Thus, based on this study, the N atom is an important pharmacophoric element in the binding of phenylalkylpiperidines and phenylalkylpiperazines to sigma receptors.
Ablordeppey
S Y
SY
College of Pharmacy & Pharmaceutical Sciences, Florida A&M University, Tallahassee 32307, USA. sablordeppey@famu.edu
Fischer
J B
JB
Glennon
R A
RA
D000818:Animals; D006168:Guinea Pigs; D007700:Kinetics; D008024:Ligands; D008954:Models, Biological; D015394:Molecular Structure; D009584:Nitrogen / Q000737:chemistry*; D010879:Piperazines / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism*; D010880:Piperidines / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism*; D011869:Radioligand Assay; D017480:Receptors, sigma / Q000737:chemistry / Q000378:metabolism*; D013329:Structure-Activity Relationship
D008024:Ligands; D010879:Piperazines; D010880:Piperidines; D017480:Receptors, sigma; D009584:Nitrogen