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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)
Author(s) -
Settimj Guido,
Del Giudice Maria Rosaria,
Ferretti Rosella,
Gatta Franco
Publication year - 1988
Publication title -
journal of heterocyclic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.321
H-Index - 59
eISSN - 1943-5193
pISSN - 0022-152X
DOI - 10.1002/jhet.5570250524
Subject(s) - chemistry , nitro , acetylation , stereochemistry , benzodiazepine , nitration , medicinal chemistry , receptor , organic chemistry , biochemistry , alkyl , gene
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‐acylamino 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‐acylamino‐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 rabbit brain benzodiazepine receptor sites indicate compounds 9b and 9c to inhibit the 3 H‐diazepam binding at 10 −8 M concentrations.