Valine-containing pseudopeptides with antiviral activity

A valine-containing, substituted pseudopeptide of the formula ##STR130## in which a represents a number 2 or 3,

• b represents a number 0 or 1,
• R.sup.1 represents hydrogen, or represents a radical of the formula R.sup.8 --NR.sup.9 --CO--, R.sup.10 --(CH.sub.2).sub.c --CO--, R.sup.11 --(CH.sub.2).sub.d --O--CO, or represents a radical of the formula --SO.sub.2 --R.sup.12,
• in which
• R.sup.8 denotes cycloalkyl having 3 to 6 carbon atoms;
• or denotes optionally substituted straight-chain or branched alkyl having up to 18 carbon atoms wherein the substituents are hydroxyl, straight-chain or branched alkoxy having up to 4 carbon atoms, halogen, trifluoromethyl, trifluoromethoxy, cycloalkyl having 3 to 6 carbon atoms, aryl having 6 to 10 carbon atoms which is optionally substituted identically or differently up to two times wherein the substituents are carboxyl, cyano, hydroxyl, halogen, C.sub.1 -C.sub.5 perhalogenoalkyl straight-chain or branched C.sub.1 -C.sub.6 acyl, straight-chain or branched C.sub.1 -C.sub.6 alkoxy, straight-chain or branched C.sub.1 -C.sub.6 alkoxycarbonyl or alkyl which is optionally substituted by a group of the formula --CO.sub.2 R.sup.13
• in which
• R.sup.13 denotes hydrogen, or straight-chain or branched alkyl or alkenyl having in each case up to 8 carbon atoms which are optionally substituted by phenyl,
• or
• R.sup.8 denotes aryl having 6 to 10 carbon atoms which is optionally substituted identical or differently up to three times by carboxyl, amino, halogen, hydroxyl, cyano, C.sub.1 -C.sub.5 perhalogenoalkyl straight-chain or branched C.sub.1 -C.sub.6 acyl, straight-chain or branched C.sub.1 -C.sub.6 alkoxy, vinyl-C.sub.1 -C.sub.6 -alkoxycarbonyl, straight-chain or branched alkoxycarbonyl, or
• denotes an amino acid radical of the formula, ##STR131## in which R.sup.14 and R.sup.15 are identical or different and denote hydrogen or methyl, or
• R.sup.14 and R.sup.15 together form a 5- or 6-membered saturated carbocyclic ring,
• or
• R.sup.14 denotes hydrogen or methyl,
• and
• R.sup.15 denotes cycloalkyl having 3 to 8 carbon atoms, aryl having 6 to 10 carbon atoms, or hydrogen;
• or denotes straight-chain or branched alkyl having up to 8 carbon atoms, where the alkyl is optionally substituted bymethylthio, hydroxyl, mercapto, guanidyl, or by a group of the formula --NR.sup.17 R.sup.18 or R.sup.19 --OC--,
• in which
• R.sup.17 and R.sup.18, independently of each other, denote hydrogen, straight-chain or branched alkyl having up to 8 carbon atoms, or phenyl,
• and
• R.sup.19 denotes hydroxyl, benzyloxy, alkoxy having up to 6 carbon atoms, or the above-listed group --NR.sup.17 R.sup.18,
• R.sup.16 denotes straight-chain or branched alkyl having up to 8 carbon atoms which is optionally substituted by hydroxyl or by straight-chain or branched alkoxy having up to 6 carbon atoms;
• or denotes carboxyl, allyloxycarbonyl, straight-chain or branched alkoxycarbonyl having up to 8 carbon atoms, or benzyloxycarbonyl;
• or the alkyl is optionally substituted by cycloalkyl having 3 to 8 carbon atoms or by optionally substituted aryl having 6 to 10 carbon atoms wherein the substituents are hydroxyl, halogen, nitro, C.sub.1 -C.sub.8 alkoxy or by the group --NR.sup.17 R.sup.18,
• in which
• R.sup.17 and R.sup.18 have the abovementioned meanings;
• or the alkyl group is optionally substituted by a 5- to 6-membered nitrogen-containing heterocycle or indolyl in which the corresponding --NH-functions are optionally protected by alkyl having up to 6 carbon atoms by an amino protecting group,
• or
• R.sup.8 denotes a radical of the formula ##STR132## in which L denotes phenyl or pyridyl,
• R.sup.9 denotes hydrogen, straight-chain or branched alkyl having up to 6 carbon atoms, or an amino protecting group,
• R.sup.10 denotes straight-chain or branched alkyl having up to 8 carbon atoms, C.sub.6 -C.sub.10 -aryloxy, C.sub.6 -C.sub.10 aryl, indolyl, quinolyl, quinoxalinyl, isoquinolyl or a 5- to 7-membered, saturated or unsaturated heterocycle having up to 3 heteroatoms selected from the group consisting of S, N or O, wherein said aryloxy, aryl and heterocyclic rings are optionally substituted identically or differently up to 3 times by carboxyl, cyano, hydroxyl, halogen, amino, nitro, methylamino, C.sub.1 -C.sub.5 perhalogenoalkyl, straight-chain or branched C.sub.1 -C.sub.6 alkyl, straight-chain or branched C.sub.1 -C.sub.5 acyl, straight-chain or branched C.sub.1 -C.sub.6 alkoxy or straight-chain or branched C.sub.1 -C.sub.6 alkoxycarbonyl,
• and additionally said aryl group is also optionally substituted by an optionally phenyl substituted 5- to 7-membered, saturated or unsaturated heterocycle having up to 3 heteroatoms selected from the group consisting of S, N or O,
• or
• R.sup.10 denotes a radical of the formula ##STR133## in which L' has the abovementioned meaning of L and is identical to our different from the latter,
• R.sup.20 denotes phenyl or naphthyl,
• c denotes a number 0, 1, 2 or 3,
• d denotes a number 0, 1, 2 or 3,
• R.sup.11 has the abovementioned meaning of R.sup.10 and is identical to or different from the latter,
• R.sup.12 denotes methyl, phenyl or naphthyl which is optionally substituted identically or differently up to 4 times by methyl or methoxy;
• or denotes a radical of the formula ##STR134## R.sup.2, R.sup.3, R.sup.5 and R.sup.6 are identical or different and represent hydrogen, straight-chain or branched alkyl having up to 4 carbon atoms, or represent an amino protecting group,
• R.sup.4 represents nitro, an amino protecting group, or radical of the formula --SO.sub.2 R.sup.21,
• in which
• R.sup.21 has the abovementioned meaning of R.sup.12 and is identical to or different from the latter,
• R.sup.7 represents formyl or carboxyl, or represents straight-chain or branched alkoxycarbonyl having up to 8 carbon atoms, or represents a radical of the formula --CH.sub.2 --OR.sup.22 or --CH(OR.sup.23).sub.2,
• in which
• R.sup.22 and R.sup.23 are identical or different and denote hydrogen, straight-chain or branched alkyl having up to 6 carbon atoms, or a hydroxyl protecting group, wherein said hydroxyl protecting group is selected from the group consisting of tert-butoxydiphenylsily, trimethylsilyl, triethylsilyl, triisopropylsilyl, tert-butyl-dimethylsilyl, tert-butyldiphenylsilyl, triphenylsilyl, trimethylsilylethoxycarbonyl, benzyl, benzyloxycarbonyl, 2-nitrobenzyl, 4-nitrobenzyl, 2-nitrobenzyloxycarbonyl, 4-nitrobenzyloxycarbonyl, tert-butyloxycarbonyl, allyloxycarbonyl, 4-methoxybenzyl, 4-methoxybenzyloxycarbonyl, formyl, acetyl, trichloroacetyl, 2,2,2-trichloroethoxycarbonyl, 2,4-dimethoxybenzyl, 2,4-dimethoxybenzyloxycarbonyl, methylthiomethyl, methoxyethoxymethyl, [2-(trimethylsilyl)ethoxy]methyl, 2-(methylthiomethoxy)ethoxycarbonyl, benzoyl, 4-methylbenzoyl, 4-nitrobenzoyl, 4-fluorobenzoyl, 4-chlorobenzoyl or 4-methoxybenzoyl
• or a salt thereof, and
• wherein said amino protecting groups are selected from the group consisting of benzyloxycarbonyl 3,4-dimethoxybenzyloxycarbonyl, 3,5-dimethoxybenzyloxycarbonyl, 2,4-dimethoxybenzyloxycarbonyl, 4-methoxybenzyloxycarbonyl, 4-nitrobenzyloxycarbonyl, 2-nitrobenzyloxycarbonyl, 2-nitro-4,5-dimethoxybenzyloxycarbonyl, methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, isopropoxycarbonyl, butoxycarbonyl, isobutoxycarbonyl, tert-butoxycarbonyl, allyloxycarbonyl, vinyloxycarbonyl, 2-nitrobenzyloxycarbonyl, 3,4,5-trimethoxybenzyloxycarbonyl, cyclohexyloxycarbonyl, 1,1-dimethylethoxycarbonyl, adamantylcarbonyl, phthaloyl, 2,2,2-trichloroethoxycarbonyl, 2,2,2-trichloro-tert-butoxycarbonyl, menthyloxycarbonyl, phenoxycarbonyl, 4-nitrophenoxycarbonyl, fluorenyl-9-methoxycarbonyl, formyl, acetyl, propionyl, pivaloyl, 2-chloroacetyl, 2-bromoacetyl, 2,2,2-trifluoroacetyl, 2,2,2-trichloroacetyl, benzoyl, 4-chlorobenzoyl, 4-bromobenzoyl, 4-nitrobenzoyl, phthalimido, isovaleroyl, or benzyloxymethylene, 4-nitrobenzyl, 2,4-dinitrobenzyl or 4-nitrophenyl.
• with the proviso that if a represents the number 2, b represents the number 1 and R.sup.5 represents hydrogen, R.sup.1 may not denote the radical of the formula R.sup.8 --NH--CO--.