N-hydroxyalkyl derivatives of 3 beta-phenyltropane and 1-methylspiro[1H-indoline-3,4'-piperidine]: vesamicol analogues with affinity for monoamine transporters.
As part of our ongoing structure-activity studies of the vesicular acetylcholine transporter ligand 2-(4-phenylpiperidino)cyclohexanol (vesamicol, 1), 22 N-hydroxy(phenyl)alkyl derivatives of 3 beta-phenyltropane, 6, and 1-methylspiro[1H-indoline-3,4'-piperidine], 7, were synthesized and tested for binding in vitro. Although a few compounds displayed moderately high affinity for the vesicular acetylcholine transporter, no compound was more potent than the prototypical vesicular acetylcholine transporter ligand vesamicol. However, a few derivatives of 6 displayed higher affinity for the dopamine transporter than cocaine. We conclude that modification of the piperidyl fragment of 1 will not lead to more potent vesicular acetylcholine transporter ligands.
Efange
S M
SM
Department of Radiology, University of Minnesota, Minneapolis 55455, USA. efang001@maroon.tc.umn.edu
Kamath
A P
AP
Khare
A B
AB
Kung
M P
MP
Mach
R H
RH
Parsons
S M
SM
D000779:Anesthetics, Local / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism*; D003042:Cocaine / Q000378:metabolism / Q000494:pharmacology; D050483:Dopamine Plasma Membrane Transport Proteins; D006168:Guinea Pigs; D007700:Kinetics; D008297:Male; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D008968:Molecular Conformation; D009419:Nerve Tissue Proteins; D009467:Neuromuscular Depolarizing Agents / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology*; D018377:Neurotransmitter Agents / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology; D010880:Piperidines / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013329:Structure-Activity Relationship; D014326:Tropanes / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology*; D050494:Vesicular Acetylcholine Transport Proteins; D033921:Vesicular Transport Proteins
D000779:Anesthetics, Local; D002352:Carrier Proteins; D050483:Dopamine Plasma Membrane Transport Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D009467:Neuromuscular Depolarizing Agents; D018377:Neurotransmitter Agents; D010880:Piperidines; C493461:Slc18a3 protein, rat; D014326:Tropanes; D050494:Vesicular Acetylcholine Transport Proteins; D033921:Vesicular Transport Proteins; C006189:vesamicol; D003042:Cocaine