PYRIDINONE DERIVATIVES AS TISSUE TRANSGLUTAMINASE INHIBITORS Russian patent published in 2018 - IPC C07D213/75 C07D401/06 C07D401/12 C07D405/12 C07D409/12 C07D413/12 C07D417/12 A61K31/341 A61K31/381 A61K31/40 A61K31/4164 A61K31/4545 A61P1/00 

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of formula (I):

,

where E¹, E² independently of each other are –CO– or –SO₂–, R^* is one of the following residues: –H, –CH₃, –C₂H₅, –C₃H₇, –CH(CH₃)₂ or –C₄H₉, R^# is one of the following residues: –NYY’, –OH, –OY, –NH–CH(CH₂CH(CH₃)₂)–CH₂COOY’,

, , , , , , ,

Y is one of the following residues: –CH₂R¹, –CHR¹–CH₂R², –CHR¹–CHR²–CH₂R³, –CHR¹–CHR²–CHR³–CH₂R⁴ or –CHR¹–CHR²–CHR³–CHR⁴–CH₂R⁵; Y’, R¹⁷-R²⁰ are selected independently of each other from: –H, –CH₃, –C₂H₅, –C₃H₇, –CH(CH₃)₂, –C₄H₉, –CH₂–CH(CH₃)₂, –CH(CH₃)–C₂H_5, –C(CH₃)₃, –C₅H₁₁, –CH₂–C(CH₃)₃, –CH(C₂H₅)₂ and –C₂H₄–CH(CH₃)₂; X is –CR⁷R⁸R⁹, –CH₂R⁷, –CHR⁷–CH₂R⁸, –O–CH₂R⁷, –O–CR⁷R⁸R⁹,

, , , , , , , , , , , , , , , , , , ,

Z is: –CH₃, –C₂H₅, –C₃H₇, –CH(CH₃)₂, –C₄H₉, –OCH₃, –OC₂H₅, –OC₃H₇, –OCH(CH₃)₂, –OC₄H₉ or –OCH₂–Ph; R¹-R¹⁰ are independently the following groups –H, –OH, –NO₂, -F, –Cl, –Br, –I, –COOH, –COOCH₃, –COOC₂H₅, –COOC₃H₇, COOCH(CH₃)₂, –COOC(CH₃)₃, –NHCOCH₃, –NHCOC₂H₅, –NHCOC₃H₇, –NHCO–OC(CH₃)₃, –NH₂, –NHCH₃, –NHC₂H₅, –NHC₃H₇,–NHCH(CH₃)₂, –NHC(CH₃)₂, –N(CH₃)₂, –N(C₂H₅)₂, –N(C₃H₇)₂, –N[CH(CH₃)₂]₂, –N[C(CH₃)₃]₂, –SO₂NH₂, –NH–CO–NH₂, –CF₃, cyclo-C₃H₅, cyclo-C₄H₇, cyclo-C₅H₉, cyclo-C₆H₁₁, –Ph, –CH₂–Ph, –CH₃, –C₂H₅, –C₃H₇, –CH(CH₃)₂, –C₄H₉, –CH₂–CH(CH₃)₂, –CH(CH₃)–C₂H_5, –C(CH₃)₃, –C₅H₁₁, –CH₂–C(CH₃)₃, –CH(C₂H₅)₂, –C₆H₁₃,

, , , , , , , , , , , ,

EFFECT: residues R¹¹-R¹⁶ are independently the following groups: –H, –NH₂, –OH, –OCH₃, –OC₂H₅, –OC₃H₇, –OCF₃, –CF₃, –F, –Cl, –Br, –I, –CH₃, –C₂H₅, –C₃H₇ and –CH(CH₃)₂; their pharmaceutically acceptable salts and their use for the prevention and treatment of diseases associated with tissue transglutaminase.

12 cl, 3 dwg, 79 ex