NUCLEOSID ARYLPHOSPHORAMIDATES AND THEIR USE AS ANTIVIRAL AGENTS FOR THE TREATMENT OF HEPATITIS VIRUS C.

摘要

A compound of formula I: in which: Ar is naphthyl; T is selected from the group consisting of hydrogen (-H), fluorine (-F), azido (N3-), amino (-NH2), hydroxy (-OH), C1-3 (C1-3-) alkyl, alkoxy C1-3 (C1-3-O- alkyl), mercapto (-SH) and C1-3 alkyl thio (C1-3 S- alkyl); V is selected from the group consisting of -OT ', hydrogen (-H), fluorine (-F) and chlorine (-Cl), in which T' is selected from the group consisting of hydrogen (-H), methyl ( -CH3), C1-16 alkylcarbonyl (C1-16 alkyl (= O) -), C2-18 alkenyl carbonyl (C2-18 alkenyl - (= O) -), C1-10 alkoxycarbonyl (C1- alkyl 10-OC (= O) -), C3-6 cycloalkyl carbonyl (C3-6-cycloalkyl (= O) -) and C3-6 cycloalkyl oxycarbonyl (C3-6-OC cycloalkyl (= O) -); T "is selected from the group consisting of hydrogen (-H), methyl (-CH3), C1-16 alkylcarbonyl (C1-16 alkyl (= O) -), C2-18 alkenyl carbonyl (C2-18 alkenyl -C (= O) -), C1-10 alkoxycarbonyl (C1-10 alkyl (= O) -), C3-6 cycloalkyl carbonyl (C3-6 -cycloalkyl -C (= O) -) and C3- cycloalkyl 6 oxycarbonyl (C3-6-OC cycloalkyl (= O) -); n is 0 or 1, where when n is 1, X is = O, and when n is 0, there is a double bond between position 3 and position 4 and X is selected from the group consisting of H, OH, F, Cl, Br, I, C1-6 alkyl and NR5R6, in which each of R5 and R6 is independently selected from H and C1-6 alkyl ; Z is selected from the group consisting of H, OH, F, Cl, Br, I, C1-6 alkyl and NR5R6, wherein each of R5 and R6 is independently selected from H and C1-6 alkyl; Y is selects from the group consisting of H, OH, F, Cl, Br, I, C1-6 alkyl, C2-8 alkynyl and NR5R6, wherein each of R5 and R6 is independently selected from H and C1-6 alkyl; Q is selected from group consisting of O, S and CR7R8, wherein R7 and R8 are independently selected from H and C1-6 alkyl; each of R1 and R2 is independently selected from H, and the group consisting of C1-20 alkyl, C2-20 alkenyl, C1-20 alkoxy, C1-20 alkoxy C1-20 alkyl, C1-20 alkoxy C6-30 aryl , C2-20 alkynyl, C3-20 cycloalkyl C6-30 aryl, C6-30 aryloxy, C5-20 heterocyclyl; each of R3 and R4 is independently selected from H, and the group consisting of C1-20 alkyl, C2-20 alkenyl, C1-20 alkoxy, C1-20 alkoxy C1-20 alkyl, C1-20 alkoxy C6-30 aryl , C2-20 alkynyl, C3-20 cycloalkyl C6-30 aryl, C6-30 aryloxy, C5-20 heterocyclyl; with the proviso that R1 and R4 together may comprise an alkylene chain - (CH2) 3; wherein alkyl is a monovalent, saturated, linear or branched acyclic or cyclic hydrocarbon radical, alkenyl is an unsaturated, linear or branched monovalent acyclic or cyclic hydrocarbon radical having one or more C = C double bonds and alkynyl is an acyclic hydrocarbon radical or monovalent, unsaturated, linear or branched cyclic having one or more C≡C triple bonds; and wherein alkyl, alkenyl or alkynyl may be optionally substituted with one, two, three or more substituents selected from the group consisting of hydroxy, acyl, acyloxy, nitro, amino, amido, -SO3 -H, -SH and -SR ', wherein R' is independently selected from R1, C1-6 carboxyl esters, C1-6 aldehyde, cyano, C1-6 amino alkyl, C1-6 dialkyl amino, thiol, chlorine, bromine, fluorine, iodine, cycloalkyl C5-7, C5-7 cycloalkenyl, C5-7 cycloalkynyl, C5-11 aryl, C5-11 aryl C1-6 alkyl and C5-20 heterocyclyl; and its pharmaceutically acceptable salts and solvates.