New insights in the discovery of novel h-MAO-B inhibitors: structural characterization of a series of N-phenyl-4-oxo-4H-chromene-3-carboxamide derivatives

Six N-substituted-phenyl 4-oxo-4H-chromene-3-carboxamides, namely N-(2-nitro-phen-yl)-4-oxo-4H-chromene-3-carboxamide, C16H10N2O5 (2b), N-(3-meth-oxy-phen-yl)-4-oxo-4H-chromene-3-carboxamide, C17H13NO4, (3a), N-(3-bromo-phen-yl)-4-oxo-4H-chromene-3-carboxamide, C16H10BrNO3, (3b), N-(4-methoxy-phen-yl)-4-oxo-4H-chromene-3-carboxamide, C17H13NO4, (4a), N-(4-methyl-phen-yl)-4-oxo-4H-chromene-3-carboxamide, C17H13NO3, (4d), and N-(4-hy-droxy-phen-yl)-4-oxo-4H-chromene-3-carboxamide, C16H11NO4, (4e), have been structurally characterized. All compounds exhibit an anti conformation with respect to the C-N rotamer of the amide and a trans-related conformation with the carbonyl groups of the chromone ring of the amide. These structures present an intra-molecular hydrogen-bonded network comprising an N-H⋯O hydrogen bond between the amide N atom and the O atom of the carbonyl group of the pyrone ring, forming an S(6) ring, and a weak Car-H⋯O hydrogen bond in which the carbonyl group of the amide acts as acceptor for the H atom of an ortho-C atom of the exocyclic phenyl ring, which results in another S(6) ring. The N-H⋯O intra-molecular hydrogen bond constrains the carboxamide moiety such that it is virtually coplanar with the chromone ring.