Variations of acidic functions at position 2 and substituents at positions 4, 5 and 6 of the indole moiety and their effect on NMDA-glycine site affinity.
The synthetic procedures to obtain indole derivatives with different acidic functions at position 2 of the indole are reported. The synthesised and tested derivatives comprise 5-tetrazolyl, 1,3,4-oxadiazol-5-yl-2-one, and indole-2-carboxylic acid amides with 5-aminotetrazole, methanesulphonamide and trifluoromethanesulphonamide moieties. The binding affinity was evaluated using [3H]MDL 105,519 and pig cortical brain membranes. In general, compounds with acidic functions different from a carboxylic acid moiety are less potent than indole-2-carboxylic acid derivatives. Also, the 4,6-dichloro substitution pattern was compared to 5-tert-butyl derivatives and compounds not substituted in the benzene moiety of the indole, indicating that the affinity increases from 5-tert-butyl over unsubstituted to 4,6-dichloro substituted derivatives.
Department of Medicinal and Pharmaceutical Chemistry, Institute of Pharmacy, Johannes Gutenberg-University, Staudinger Weg 5, 55099 Mainz, Germany.
Michaela
M
Jansen
Gerd
G
Dannhardt
D000818:Animals; D001665:Binding Sites; D002462:Cell Membrane / Q000737:chemistry; D002540:Cerebral Cortex / Q000737:chemistry; D005998:Glycine; D007211:Indoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D020128:Inhibitory Concentration 50; D008958:Models, Molecular; D011869:Radioligand Assay; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000737:chemistry*; D013329:Structure-Activity Relationship; D013552:Swine
D007211:Indoles; C101788:MDL 105519; D016194:Receptors, N-Methyl-D-Aspartate; D005998:Glycine