INHIBITORS - AMINO - CARBOXYMUCONATE - SEMIALDEHYDE - DECARBOXYLASE Russian patent published in 2021 - IPC C07D239/38 C07D239/56 C07D401/04 C07D403/12 C07D405/04 C07D409/04 C07D409/14 A61K31/505 A61K31/506 A61P13/12 A61P25/28 A61P29/00 

FIELD: pharmaceuticals.

SUBSTANCE: invention relates to a compound represented by Formula (I), or a pharmaceutically acceptable salt or tautomer thereof, which can be used as α-amino carboxymuconate semialdehyde decarboxylase (ACMSD) inhibitors. In Formula (I) X represents O, OH or Cl; L represents -(CH₂)_mY(CH₂)_p-; Y represents NH or S(O)_q; R¹ represents C₆aryl, where aryl is substituted with R^a and R^b and is optionally substituted with one or more R^e; one of R^a and R^b represents hydrogen and the other one represents -(CH₂)_rCO₂R^x, -(CH₂)_rtetrazole or -(CH₂)_roxadiazolone; R^c is a halogen or -CN; R^d is a methyl, phenyl, 5-or 6-membered heteroaryl containing one or two heteroatoms selected from nitrogen and sulfur, or 5- or 6-memebered carcocycle; each R^x at each occurrence independently represents hydrogen or (C₁-C₆)alkyl; each R^e independently represents (C₁-C₆)alkyl, (C₂-C₆)alkenyl, (C₂-C₆)alkynyl, halogen, -OR^y, (C₁-C₆)haloalkyl, -NHR^z, -OH or -CN; R^f represents H or missing; each R^y and R^z independently represents hydrogen, (C₁-C₆)alkyl or (C₁-C₆)haloalkyl; each m and p is independently equal to 0, 1 or 2, wherein m+p <3; q equals to 0, 1 or 2; r is equal to 0 or 1; and the dashed line represents an optional double link; provided that R^с is not -CN, when X represents O, L represents -SCH₂-, and R^d is phenyl. The invention also relates to a pharmaceutical composition having the properties of an inhibitor of α-amino-β-carboxymuconate-ε-semialdehyde-decarboxylase (ACMSD) and the ability to increase the level of nicotinamide adenine dinucleotide (NAD⁺), including a therapeutically effective amount of the specified compound and at least one pharmacologically acceptable carrier, diluent, or excipient, and to a method for treating a disease or disorder by inhibitingα-amino-β-carboxymuconate-ε-semialdehyde-decarboxylase (ACMSD), which involves injecting a subject suffering from or susceptible to developing a disease or disorder associated with ACMSD dysfunction with a therapeutically effective amount of the specified compound.

EFFECT: invention helps in treatment of a disease or disorder associated with ACMSD dysfunction.

(I)

34 cl, 8 dwg, 2 tbl, 49 ex