β-carbolines as agonistic or antagonistic benzodiazepine receptor ligands. 1. Synthesis of some 5-, 6- and 7-amino derivatives of 3-methoxycarbonyl-β-carboline (β-CCM) and of 3-ethoxycarbonyl-β-carboline (β-CCE)

Article abstract of DOI:10.1002/jhet.5570250524

Condensation of diethyl formylamino- or diethyl acetylaminomalonate with 4-, 5- or 6-nitrogramine 1 afforded the diethyl formylamino- or the diethyl acetylamino[(nitroindol)-3-ylmethyl]malonates 2; reduction of the nitro group followed by N-formylation or acetylation of the resulting amino compounds 3, led to the 4-, 5-and 6-acrylamino derivatives 4. Cyclization of 4 in the presence of polyphosphoric esters gave the 3,3-bis(ethoxycarbonyl)-3,4-dihydro-β-carbolines 5, which underwent lithium chloride/water catalyzed monodeethoxycarbonylation to the corresponding 5-, 6- and 7-acrylamino-3-ethoxycarbonyl-β-carbolines 6, whose acidic hydrolysis led finally to the 5-, 6- and 7-amino-3-ethoxycarbonyl-β-carbolines 9. The 6-amino compounds 9b-e were obtained also by direct nitration of 3-methoxycarbonyl-β-carboline 7a and of 3-ethoxycarbonyl-β-carboline 7c, followed by the nitro group reduction of the resulting nitro carbolines 8. Preliminary studies of the binding to the rabbit brain benzodiazepine receptor sites indicate compounds 9b and 9c to inhibit the ³H-diazepam binding at 10^-8 M concentrations.