Potentially biologically active new substituted anilides of benzo[2,3-b]thiophene series

Abstract

New substituted anilides of the heterocyclic series 2, 4, 5, 6, 7 together with the earlier described compounds 1 and 3 (Jarak I et al. (2005) J Med Chem 48:2346), were synthesized from the corresponding heterocyclic carbonyl chlorides, methoxycarbonyl- and cyano-substituted anilines. Compounds 2 and 7 were prepared by methylation with methyl-iodide on the amide and the pyridine nitrogen. The Pinner reaction was used in the preparations of amidino-substituted compounds. It seems that all the prepared compounds could be biologically interesting, especially amidino-substituted anilides prepared in the form of water-soluble hydrochlorides or hydroiodides.

Molecular and crystal structures of the three compounds, namely, 4′-methoxycarbonyl-N-phenyl-3-chlorobenzo[b]thiophene-2-carboxamide (1), N-(4′-amidinophenyl)-3-chlorobenzo[b]thiophene-2-carboxamide hydrochloride monohydrate (4) and 1-methyl-N-(4-amidinophenyl)-3-pyridine carboxamide iodide hydroiodide (7) have been determined by X-ray single-crystal diffractometry in the solid state. Compounds 1, 4 and 7 are not planar and the amide group (C=O in relation to NH group) is in trans position in all three compounds. The 3-chlorobenzo[b]thiophene moiety in 1 and 4 is oriented with the chloro substituent in cis position in relation to amide NH group. The conformational characteristics of the compounds result from the introduction of different substituents or solvent molecules (water molecule in 4), which leads to various intermolecular hydrogen bonds formation (N–H⋯O, N–H⋯Cl, O–H⋯Cl⁻, N–H⋯I⁻) in 1, 4 and 7. Hydrogen bond formation could be responsible for the potential biological activity of the compounds.