title: Synthesis and structure-activity relationship studies of 3-biaryl-8-oxabicyclo[3.2.1]octane-2-carboxylic acid methyl esters.
abstract: Stille cross coupling protocols were utilized for the synthesis of 3-(biaryl)-8-oxabicyclo[3.2.1]oct-2-ene-2-carboxylic acid methyl esters, which furnished products in high yields where in some cases Suzuki coupling under the conditions utilized provided complex reaction mixture. Samarium iodide reduction of the resulting coupling products produced both of the 2β-carbomethoxy-3-biaryl-8-oxabicyclo[3.2.1]octane diastereomers and the 2α-carbomethoxy-3-biaryl-8-oxabicyclo[3.2.1]octane diastereomers. Among the series synthesized, the benzothiophene substituted compounds demonstrated significant binding profiles of inhibition of WIN 35,438 with 177-fold selectivity for DAT versus SERT.
authors.affiliation: TUBITAK MAM Chemistry Institute P K 21 Gebze, Kocaeli 41470, Turkey. lokman.torun@mam.gov.tr
authors.forename: Lokman
authors.initials: L
authors.lastname: Torun
authors.forename: Bertha K
authors.initials: BK
authors.lastname: Madras
authors.forename: Peter C
authors.initials: PC
authors.lastname: Meltzer
mesh_terms: D001643:Bridged Bicyclo Compounds / Q000737:chemistry*; D002264:Carboxylic Acids / Q000737:chemistry*; D003042:Cocaine / Q000031:analogs & derivatives / Q000494:pharmacology; D050483:Dopamine Plasma Membrane Transport Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D018765:Dopamine Uptake Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D004952:Esters / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D015394:Molecular Structure; D050486:Serotonin Plasma Membrane Transport Proteins / Q000378:metabolism; D017367:Selective Serotonin Reuptake Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D001643:Bridged Bicyclo Compounds; D002264:Carboxylic Acids; D003042:Cocaine; D050483:Dopamine Plasma Membrane Transport Proteins; D018765:Dopamine Uptake Inhibitors; D004952:Esters; D050486:Serotonin Plasma Membrane Transport Proteins; D017367:Selective Serotonin Reuptake Inhibitors; C021279:(1R-(exo,exo))-3-(4-fluorophenyl)-8-methyl-8- azabicyclo(3.2.1)octane-2-carboxylic acid, methyl ester