Synthesis and structure–activity relationship studies of 3-biaryl-8-oxabicyclo[3.2.1]octane-2-carboxylic acid methyl esters

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 red...

Full description

Saved in:
Bibliographic Details
Published in:Bioorganic & medicinal chemistry 2012-04, Vol.20 (8), p.2762-2772
Main Authors: Torun, Lokman, Madras, Bertha K., Meltzer, Peter C.
Format: Article
Language:English
Subjects:
Biological and medical sciences
Bridged Bicyclo Compounds - chemistry
Carboxylic Acids - chemistry
Cocaine - analogs & derivatives
Cocaine - pharmacology
Cocaine medications
diastereomers
Dopamine Plasma Membrane Transport Proteins - antagonists & inhibitors
Dopamine Plasma Membrane Transport Proteins - metabolism
Dopamine Uptake Inhibitors - chemical synthesis
Dopamine Uptake Inhibitors - chemistry
Dopamine Uptake Inhibitors - pharmacology
Drug addictions
esters
Esters - chemical synthesis
Esters - chemistry
Esters - pharmacology
General pharmacology
Humans
iodides
Medical sciences
Molecular Structure
Monoamine transporter ligands
octane
Oxatropanes
Pharmacology. Drug treatments
Physicochemical properties. Structure-activity relationships
samarium
Selective Serotonin Reuptake Inhibitors - chemical synthesis
Selective Serotonin Reuptake Inhibitors - chemistry
Selective Serotonin Reuptake Inhibitors - pharmacology
Serotonin Plasma Membrane Transport Proteins - metabolism
Serotonin transporter
Stille coupling
Structure-Activity Relationship
Structure-activity relationships
Suzuki coupling
Toxicology
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:0968-0896
1464-3391
DOI:10.1016/j.bmc.2012.01.053