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)

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Abstract
Condensation of diethyl formylamino‐ or diethyl acetylaminomalonate with 4‐, 5‐ or 6‐nitrogramine1afforded the diethyl formylamino‐ or the diethyl acetylamino[(nitroindol)‐3‐ylmethyl]malonates2; reduction of the nitro group followed byN‐formylation or acetylation of the resulting amino compounds3, led to the 4‐, 5‐and 6‐acylamino derivatives4.Cyclization of4in the presence of polyphosphoric esters gave the 3,3‐bis(ethoxycarbonyl)‐3,4‐dihydro‐β‐carbolines5, which underwent lithium chloride/water catalyzed monodeethoxycarbonylation to the corresponding 5‐, 6‐ and 7‐acylamino‐3‐ethoxycarbonyl‐β‐carbolines6, whose acidic hydrolysis led finally to the 5‐, 6‐ and 7‐amino‐3‐ethoxycarbonyl‐β‐carbolines9. The 6‐amino compounds9b‐ewere obtained also by direct nitration of 3‐methoxycarbonyl‐β‐carboline7aand of 3‐ethoxycarbonyl‐β‐carboline7c, followed by the nitro group reduction of the resulting nitro carbolines8.Preliminary studies of the binding to rabbit brain benzodiazepine receptor sites indicate compounds9band9cto inhibit the3H‐diazepam binding at 10−8Mconcentrations.