HETEROCYCLIC MAT2A INHIBITORS AND METHODS OF THEIR USE FOR CANCER TREATMENT Russian patent published in 2023 - IPC C07D471/04 C07D487/04 C07D519/00 A61K31/5025 A61P35/00 C07B59/00 

FIELD: organic chemistry.

SUBSTANCE: group of inventions includes a compound of formula I, its pharmaceutically acceptable salt, a pharmaceutical composition containing it, a method of treatment and a method of its use. In formula (I), L represents either O, S, NR or a bond; R represents either H or C₁-C₆-alkyl; R¹ is selected from the group consisting of C₁-C₆-alkyl, C₃-C₆-cycloalkyl, -(C₁-C₆-alkyl)(C₃-C₆-cycloalkyl), where any alkyl in R¹ is straight or branched and R¹ is optionally substituted with 1-6 halogens or 1-6 deuterium; or when L is NR, then R and R¹ in combination with L are a 3-6 membered heterocycloalkyl in which 1-4 ring members are independently selected from N, O and S; R² is selected from the group consisting of C₂-C₆-alkynyl, C₆-C₁₀-aryl, C₃-C₆-cycloalkyl, C₃-C₆-cycloalkenyl, 5-10 membered heteroaryl, in which 1-4 heteroaryl members independently selected from N, O and S, where R² is optionally substituted with one substituent selected from R^A and halogen; R³ is selected from the group consisting of C₆-C₁₀-aryl, C₃-C₆-cycloalkenyl, 5-10 membered heteroaryl, in which 1-4 heteroaryl members are independently selected from N, O and S, and 3-A 6-membered heterocycloalkyl fused with a C₆-aryl, in which 1-4 heterocycloalkyl members are independently selected from N, O and S, wherein R³ is optionally substituted with one or two substituents which are selected from the group consisting of R^A, halogen, NR^AR^B, -C(O)NR^AR^B and -CN; R⁴ is selected from the group consisting of H, C₁-C₆-alkyl, optionally substituted with 1-3 halogens or 6-membered heterocycloalkoxy containing 1 heteroatom O, -(C₁-C₆-alkyl)NR^AR^B and -NR^AR^B; R⁵ is selected from H and halogen; R^A is independently selected from the group consisting of H, -hydroxy, oxo, C₁-C₆-alkyl, C₁-C₆-alkoxy, C₃-C₆-cycloalkyl and 5-10 membered heteroaryl, in which 1-4 heteroaryl members independently selected from N, O and S; wherein each alkyl and alkoxy moiety R^A is optionally substituted with 1-3 substituents selected from the group consisting of deuterium and halogen; R^B are independently selected from the group consisting of H and C₁-C₆-alkyl.

EFFECT: compound of formula (I), which has the properties of an inhibitor of methionine adenosyltransferase isoform 2A (MAT2A).

43 cl, 2 tbl, 332 ex