title: Novel 2-substituted cocaine analogs: binding properties at dopamine transport sites in rat striatum.
abstract: A novel scheme utilizing vinylcarbenoid precursors has been developed for the synthesis of novel tropane analogs of cocaine. Using this method, 15 analogs were prepared and tested for activity in binding to dopamine transporters in rat striatal membranes using [125I]RTI-55. In all the analogs, the aryl group at the 3 position was directly bound to the tropane ring (as in WIN 35,428), and methyl or ethyl ketone moieties were present at the 2 position instead of the typical ester group. The most potent analog was a 2-naphthyl derivative (IC50 value of 0.2 nM, vs. 170 nM for cocaine), while replacement of the aryl with either ethyl or cyclohexyl drastically reduced potency (to > 50 microM and 5 microM, respectively).
authors.affiliation: Department of Chemistry, Wake Forest University, Winston-Salem, NC 27109.
authors.forename: H M
authors.initials: HM
authors.lastname: Davies
authors.forename: E
authors.initials: E
authors.lastname: Saikali
authors.forename: T
authors.initials: T
authors.lastname: Sexton
authors.forename: S R
authors.initials: SR
authors.lastname: Childers
mesh_terms: D000818:Animals; D001665:Binding Sites; D001692:Biological Transport; D002352:Carrier Proteins / Q000378:metabolism*; D003042:Cocaine / Q000031:analogs & derivatives* / Q000378:metabolism; D003342:Corpus Striatum / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D050483:Dopamine Plasma Membrane Transport Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D051381:Rats; D013329:Structure-Activity Relationship
chemical_list: D002352:Carrier Proteins; D050483:Dopamine Plasma Membrane Transport Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; C069723:2beta-carbomethoxy-3beta-(4-iodophenyl)tropane; D003042:Cocaine; D004298:Dopamine