Bicyclo[3.2.1]octanes: synthesis and inhibition of binding at the dopamine and serotonin transporters.
Herein we report the synthesis of a series of bicyclo[3.2.1]octanes and their binding characteristics at the dopamine and serotonin transporters. The data confirm that a heteroatom at position 8 of the tropane nucleus is not a prerequisite for binding since the bicyclo[3.2.1]octanes prove potent inhibitors of both transporters. Therefore the three-dimensional topology of the ligand may be more important than specific functionality with respect to stereospecific binding at the acceptor site.
Meltzer
P C
PC
Organix Inc, Woburn, MA 01801, USA.
Blundell
P
P
Chen
Z
Z
Yong
Y F
YF
Madras
B K
BK
D001643:Bridged Bicyclo Compounds / Q000138:chemical synthesis* / Q000494:pharmacology; D002352:Carrier Proteins / Q000378:metabolism*; D003042:Cocaine / Q000737:chemistry; D050483:Dopamine Plasma Membrane Transport Proteins; D020128:Inhibitory Concentration 50; D007700:Kinetics; D008562:Membrane Glycoproteins / Q000378:metabolism*; D026901:Membrane Transport Proteins; D008956:Models, Chemical; D009419:Nerve Tissue Proteins; D050486:Serotonin Plasma Membrane Transport Proteins
D001643:Bridged Bicyclo Compounds; D002352:Carrier Proteins; D050483:Dopamine Plasma Membrane Transport Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D050486:Serotonin Plasma Membrane Transport Proteins; D003042:Cocaine