Synthesis of methylphenidate analogues and their binding affinities at dopamine and serotonin transport sites.
The rhodium(II)-catalyzed intermolecular C-H insertion of methyl aryldiazoacetates with either N-Boc-piperidine or N-Boc-pyrrolidine followed by deprotection with trifluoroacetic acid is a very direct method for the synthesis of methylphenidate analogues. By using either dirhodium tetraacetate or dirhodium tetraprolinate derivatives as catalyst, either the racemic or enantioenriched methylphenidate analogues can be prepared. The binding affinities of the methylphenidate analogues to both the dopamine and the serotonin transporters are described. The most notable compounds are the erythro-(2-naphthyl) analogues which display high binding affinity and selectivity for the serotonin transporter.
Davies
Huw M L
HM
Department of Chemistry, State University of New York at Buffalo, Buffalo, NY 14260-3000, USA. hdavies@acsu.buffalo.edu
Hopper
Darrin W
DW
Hansen
Tore
T
Liu
Quixu
Q
Childers
Steven R
SR
D001665:Binding Sites; D002352:Carrier Proteins / Q000378:metabolism*; D050483:Dopamine Plasma Membrane Transport Proteins; D008562:Membrane Glycoproteins / Q000378:metabolism*; D026901:Membrane Transport Proteins / Q000378:metabolism*; D008774:Methylphenidate / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D011485:Protein Binding / Q000502:physiology; D050486:Serotonin Plasma Membrane Transport Proteins
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; D008774:Methylphenidate