SULFOXONIUM YLIDE DERIVATIVES AS PROBES FOR CYSTEINE PROTEASE Russian patent published in 2024 - IPC C07D403/06 C07D209/18 C07D209/24 G01N33/533 C09B23/08 A61K49/00 A61P1/00 A61P29/00 A61P25/00 A61P25/28 A61P35/00 

FIELD: pharmaceuticals.

SUBSTANCE: invention relates to a compound of formula I or a salt thereof, where R₁ is selected from the group consisting of (C₁-C₈) alkyl, (C₁-C₈) hydroxyalkyl, (C₁-C₈) haloalkyl, (C₃-C₈) cycloalkyl, (C₂-C₈) alkenyl and (C₂-C₈) alkynyl; R₂ is selected from the group consisting of (C₁-C₈) alkyl, (C₁-C₈) hydroxyalkyl, (C₁-C₈) haloalkyl, (C₃-C₈) cycloalkyl, (C₂-C₈) alkenyl and (C₂-C₈) alkynyl; R₃ represents a side chain of an alpha amino acid selected from the group consisting of glycine, alanine, alpha-aminobutyric acid, valine, norvaline, leucine, isoleucine, norleucine, homonorleucine, methionine, ethionine, phenylalanine, tyrosine, levodopa, tryptophan, cysteine, homocysteine, selenocysteine, selenicomocysteine, selenomethyonin, selenesetionine, lysine, hyistidine, arginine, ornithin, asparagic acid, glutamic acid, serin, homeserin, o-methylgom squeezer, o-ejolgomoserin, treonin, asparagin and glutamine, where the indicated side chain is not necessary for amino protection group and is optionally further substituted with one or more identical or different R_3x substituents, where R_3x is selected from the group consisting of hydroxy, halogen, (C₁-C₄) alkyl, (C₁-C₄) hydroxyalkyl, (C₁-C₄) haloalkyl, (C₁-C₄) alkoxy and (C₁-C₄) haloalkoxy; R₄ is selected from the group consisting of a hydrogen atom and (C₁-C₄) alkyl; R₅ represents a detectable element that is a fluorescent label that is a cyanine label; X represents: (i) connection; or (ii) a biradical fragment of formula II which is linked to the substituent R₅ through an amino group, where R₆ represents a side chain of an alpha amino acid selected from the group consisting of glycine, alanine, alpha-aminobutyric acid, valine, norvaline, leucine, isoleucine, norleucine, homonorleucine, methionine, ethionine, phenylalanine, tyrosine, levodopa, tryptophan, cysteine, homocysteine, selenocysteine, selenogomocysteine, selenomethionine, selenoethionine, lysine, histidine, arginine, ornithine, aspartic acid, glutamic acid, serine, homoserine, O- methylhomoserine, O-ethylhomoserine, threonine, asparagine and glutamine, wherein the said side chain is optionally substituted with an amino protecting group and optionally further substituted with one or more identical or different R_6x substituents, wherein R_6x is selected from the group consisting of hydroxy, halogen, (C₁-C₄) alkyl, (C₁-C₄) hydroxyalkyl, (C₁-C₄) haloalkyl, (C₁-C₄) alkoxy and (C₁-C₄) haloalkoxy; R₇ is selected from the group consisting of a hydrogen atom and (C₁-C₄) alkyl; and wherein the amino protecting group is selected from the group consisting of benzyloxycarbonyl (Cbz), 9-fluorenylmethyloxycarbonyl (Fmoc), tert-butyloxycarbonyl (Boc), allyloxycarbonyl (Alloc), p-toluenesulfonyl (Tos), 2,2,5,7,8-pentamethylchroman-6-sulfonyl (Pmc), 2,2,4,6,7-pentamethyl-2,3-dihydrobenzofuran-5-sulfonyl (Pbf), mesityl-2-sulfonyl (Mts), 4-methoxy-2,3,6-trimethylphenylsulfonyl (Mtr), acetamido, and phthalimido. The invention also relates to compositions acting as probes based on cathepsin X inhibitors containing a compound of formula I, as well as methods of detecting the activity of cathepsin X.

EFFECT: new compounds that can be used in medicine as activity-based probes for cysteine proteases such as cathepsin X, as well as methods of detecting cysteine protease activity and related diagnostic or therapeutic methods.

46 cl, 25 dwg, 1 tbl, 14 ex