NEW HETEROCYCLIC COMPOUNDS AS MONOACYLGLYCEROL LIPASE INHIBITORS Russian patent published in 2023 - IPC C07D498/04 A61K31/5365 A61P25/00 A61P25/28 A61P29/00 A61P35/00 

FIELD: organic chemistry.

SUBSTANCE: group of inventions includes a compound of formula (I), specific compounds listed in the claims, a method of preparing a compound of formula (I), the use of a compound of formula (I), a method of inhibiting MAGL, and a method of determining the MAGL inhibitory activity of a compound. In formula (I), X is C-R³; m is either 0 or 1; n is selected from 0, 1 and 2; and L is selected from -C≡C-, -CHR⁴-NR⁵-CH₂-, -CH₂-NR⁵-CHR⁴-, -(CR⁶R⁷)_p-C(O)-NR⁸-, -C(O)-NR⁸-(CR⁶R⁷)_p-, -(CR⁶R⁷)_p-NR⁸-C(O)-, -(CH₂)_qNR⁹-, -S-, -S(O)-, -SO₂-, -SCH₂-, -CH₂S-, -S(O)CH₂- and -SO₂CH₂-; each of p and q is independently selected from 0, 1 and 2; A is selected from: (i) C₆-C₁₄-aryl substituted with R¹⁰, R¹¹ and R¹²; (ii) 5–14-membered heteroaryl selected from thiophenyl and pyridinyl substituted with R¹³ and R¹⁴; and (iii) C₃-C₁₀-cycloalkyl substituted with R²²; R¹, R² are hydrogen; R³ is selected from hydrogen, hydroxy and C_1-6-alkyl; R⁴ is halo-C_1-6-alkyl; R⁵ is selected from hydrogen and C_1-6-alkyl; each of R⁶ and R⁷ independently represents hydrogen; or R⁶ and R⁷ together with the carbon atom to which they are attached form C_3-10-cycloalkyl; R⁸ is selected from hydrogen, C_1-6-alkyl and hydroxy-C_1-6-alkyl; R⁹ is C_1-6-alkyl; each of R¹⁰, R¹¹, R¹², R¹³ and R¹⁴ is independently selected from hydrogen, halogen, cyano, hydroxy, C_1-6-alkyl, halo-C_1-6-alkyl, C_1-6-alkoxy, halo-C_1-6-alkoxy, C_1-6-alkylsulfonyl, C_3-10-cycloalkyl optionally substituted with R¹⁹; R¹⁹ is independently selected from cyano and hydroxy; R²² is hydroxy.

EFFECT: compound of formula (I) with inhibitory activity against monoacylglycerol lipase (MAGL).

34 cl, 1 tbl, 16 ex