Antiviral 2,4-pyrimidinedione derivatives and process for the preparation thereof

Abstract

2,4-pyrimidinedione derivatives of formula (I) having high antiviral activity against wild-type and mutant HIV-1 and low toxicity are useful for treating AIDS (I) wherein: R is a C aryl or C heteroaryl group optionally having one or more substituents selected from the group consisting of halogen, C alkyl, C alkyl substituted with one or more halogen atoms, C cycloalkyl, cyano, nitro, hydroxy, thiohydroxy, azido, C alkoxy, oximino, C alkyloximino, O—(C alkyl)-substituted oximino, C— alkylcarbonyl, C cycloalkylcarbonyl, hydroxymethyl, azidomethlyl, C alkoxymethyl, C acyloxynethyl, carbamoyloxymethyl, anminomethyl, N—(C alkyl)aminomethyl, N,N-di(C alkyl)aminomethyl, carboxy, C alkoxycarbonyl, aziridine, amino, hydroxyethylamino, cyclopropylamino, C alkylamino, di(C alkyl)amino, trifluoroacetamido, C acylamido, carbamoyl, hydroxyethylcarbamoyl, cyclopropylcarbamoyl, C alkylcarbamoyl, di(C alkyl)carbamoyl, aminocarbamoyl, dimethylaminocarbamoyl, hydrazino, 1,1-dimethylhydrazino, imidazolyl, triazolyl and tetrazolyl; a tetrahydropyridyl or piperidyl group optionally substituted with a C alkyl or C alkoxycarbonyl group; a tetrahydropyranyl group; or a tetrahydrofuryl group; R is hydrogen, halogen, nitro, cyano, C alkoxycarbonyl, C alkylamino, di(C alkyl)amino, C alkylcarbamol, di(C alkyl)carbamoyl, C alkyl, C cycloalkyl or benzyl; R and R are each independently hydrogen, halogen, hydroxy, cyano, nitro, amino acetamido, trifluoroacetamido, azido, C alkyl, C- alkyl substituted with one or more halogen atoms, C alkoxycarbonyl, carbamoyl C alkylcarbamoyl, di(C alkyl) carbamoyl or C- alkoxy; A is O or S; and Z is O, S, C═O, NH or CH .