Four pyrrole derivatives used as building blocks in the synthesis of minor-groove binders

Abstract

The title nitropyrrole-based compounds, C7H8N2O4, (I) (ethyl 4-nitro-1Hpyrrole- 2-carboxylate), its derivative C12H14N2O4, (II) [ethyl 4-nitro-1-(4- pentynyl)-1H-pyrrole-2-carboxylate], C15H26N4O3, (III) {N-[3-(dimethyamino) propyl]-1-isopentyl-4-nitro-1H-pyrrole-2-carboxamide}, and C20H27N9O5, (IV) {1-(3-azidopropyl)-4-(1-methyl-4-nitro-1H-pyrrole-2-carboxamido)- N-[2-(morpholin-4-yl)ethyl]-1H-pyrrole-2-carboxamide}, are intermediates used in the synthesis of modified DNA minor-groove binders. In all four compounds, the nitro groups lie in the plane of the pyrrole ring. In compounds (I) and (II), the ester groups also lie in the plane of the pyrrole ring. In compound (III), both of the other substituents lie out of the plane of the pyrrole ring. In the case of compound (IV), the coplanarity extends to the second pyrrole ring and through both amide groups. In the crystals of all four compounds, layer-like structures are formed, via a combination of N—H O and C—H O hydrogen bonds for (I), (III) and (IV), but by only C—H O hydrogen bonds for (II)