Synthesis of novel sigma-receptor ligands from methyl alpha-D-mannopyranoside.
For the first time a monosaccharide (methyl alpha-D-mannopyranoside) has been used as starting material for the synthesis of novel sigma-receptor ligands. The hept-3-ulopyranoside dimethyl ketals 14 and 15 were obtained from the nitrile 7 via two synthetic routes. After selective hydrolysis of the ketone dimethyl acetal, various amino substituents were introduced into position 3. High sigma(1)-receptor affinity and selectivity was attained with equatorially arranged amino substituents in position 3 and a dichlorophenylacetamide moiety in position 7. The anomeric mixture of dimethylamines 26alpha/beta displayed the highest sigma(1)-receptor affinity (K(i)=21nM) within this small series of test compounds.
Wiedemeyer
Kathrin
K
Institut für Pharmazeutische und Medizinische Chemie der Westfälischen Wilhelms-Universität Münster, Hittorfstrasse 58-62, D-48149 Münster, Germany.
Wünsch
Bernhard
B
D006868:Hydrolysis; D008024:Ligands; D008358:Mannose / Q000737:chemistry*; D008766:Methylmannosides; D015394:Molecular Structure; D011869:Radioligand Assay; D017480:Receptors, sigma / Q000737:chemistry*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D008024:Ligands; D008766:Methylmannosides; D017480:Receptors, sigma; C008466:methylmannoside; D008358:Mannose