Patent ID: 6252041
Filing Date: 2001-06-26
Classification: A61K,C07C,C07K,Y02P

Abstract:
A depsipeptide containing a non-natural amino acid(s) having the formula (1) ##STR13##whereinR.sup.1 represents a straight or branched C.sub.5 -C.sub.20 alkyl group or a straight or branched C.sub.5 -C.sub.15 alkoxymethyl group,R.sup.2 represents--O--CO--CH(R.sup.5)--X--CH(R.sup.6)--NH(wherein X represents N(R.sup.7)--CO, N(R.sup.8)--CH.sub.2, CH.sub.2 --CO, CH.sub.2 --CH.sub.2, CH.dbd.CH, CH.sub.2 --CH(OH) or CH(OH)--CH(OH), R.sup.5, R.sup.6, R.sup.7 and R.sup.8 represent a hydrogen atom or a straight or branched C.sub.1 -C.sub.6 alkyl group),R.sup.3 represents ##STR14##(wherein Y represents N(R.sup.12)--CO, N(R.sup.13)--CH.sub.2, CH.sub.2 --CO, CH.sub.2 --CH.sub.2, CH.dbd.CH, CH.sub.2 --CH(OH) or CH(OH)--CH(OH), n represents an integer of 1-3, R.sup.9, R.sup.10, R.sup.12 and R.sup.13 represent a hydrogen atom or a straight or branched C.sub.1 -C.sub.6 alkyl group and R.sup.11 represents a protecting group for an amine commonly used in peptide chemistry),R.sup.4 represents a hydroxyl group, a straight or branched C.sub.1 -C.sub.6 alkoxy group, a benzyloxy group, A, A--B or--NH--CH(R.sup.14)--Z--CH(R.sup.15)--COR.sup.16(wherein Z represents CH.sub.2 --N(R.sup.17), CO--CH.sub.2, CO--N(R.sup.18), CH.sub.2 --CH.sub.2, CH.dbd.CH, CH(OH)--CH.sub.2 or CH(OH)--CH(OH), R.sup.14 represents a hydrogen atom, a straight or branched C.sub.1 -C.sub.6 alkyl group or --(CH.sub.2).sub.m --COR.sup.19, R.sup.15, R.sup.17 and R.sup.18 represent a hydrogen atom or a straight or branched C.sub.1 -C.sub.6 alkyl group, R.sup.16 represents a hydroxyl group, a straight or branched C.sub.1 -C.sub.6 alkoxy group or a benzyloxy group, R.sup.19 represents a hydroxyl group, an amino group or a C.sub.1 -C.sub.6 alkoxy group and m represents an integer of 1-3),A represents a residue of an amino acid selected from the group of alanine, valine, leucine, isoleucine, phenylalanine, tyrosine, proline, aspartic acid, asparagine, glutamic acid, glutamine, serine, lysine and .beta.-t-butylalanine or an N-methyl derivative of said amino acid residue,B represents a residue of an amino acid selected from the group of alanine, valine, leucine, isoleucine, serine, threonine, lysine, hydroxylysine, arginine, cysteine, methionine, phenylalanine, tyrosine, tryptophan, histidine, proline, 4-hydroxyproline, aspartic acid, asparagine, glutamic acid, glutamine, piperidine-4-carboxylic acid, homoproline, octahydroindole-2-carboxylic acid, norvaline, norleucine, .alpha.-t-butylglycine, cyclohexylglycine, azetidine-2-carboxylic acid, 3-(3-pyridyl)alanine, (3-N-methyl)piperidylalanine, 3-(2-naphthyl)alanine, .beta.-cyclohexylalanine, .beta.-t-butylalanine, 9-anthracenylalanine, .alpha.-methylalanine and 2-aminobutanoic acid or an N-methyl derivative of said amino acid residue, when the amino acid for A or B contains a free amino group, free carboxyl group, free .omega.-carbamido group, free hydroxyl group, free mercapto group and/or an N-terminal amino group, said free group may be protected by a group commonly used in peptide chemistry, respectively, and when A and B are lysine, hydroxylysine, glutamic acid or aspartic acid, either .alpha.- or .omega.-amino or carboxyl group existing in said residue may form a peptide linkage with its adjacent amino acid;with the proviso that compounds are excluded in which, simultaneously, X is N(R.sup.7)--CO, Y is N(R.sup.12)--CO and R.sup.4 is hydroxyl straight or branched alkoxy having 1-6 carbon atoms, benzyloxy, A, A--B or --NH--CH(R.sup.14)--Z--CH(R.sup.15)--COR.sup.16 (wherein Z is CO--N(R.sup.18));or a pharmacologically acceptable salt thereof.