HETEROARYL-SUBSTITUTED PIPERIDINE DERIVATIVES AS HEPATIC CARNITINE PALMITOYLTRANSFERASE (L-CPT1) INHIBITORS Russian patent published in 2010 - IPC C07D413/04 A61K31/4245 A61P3/06 A61P3/08 

FIELD: chemistry.

SUBSTANCE: invention relates to novel compounds of formula (I) , where X is C(R⁸R⁹), NR¹⁰, O, S; R¹ is phenyl which is substituted with 1-3 substitutes selected from a group which includes halogen, hydroxy group, lower alkyl, hydroxy-lower alkyl and CN; R² is hydrogenor lower alkyl; R³ and R⁴ are hydrogen; R⁵ and R⁶ are hydrogen; R⁷ is oxadiazolyl or triazolyl, where oxadiazolyl or triazolyl is substituted with R¹¹; R⁸ and R⁹ denote hydrogen; R¹⁰ denotes hydrogen, lower alkyl, lower alkyl-carbonyl or lower alkyl-sulfonyl, R¹¹ denotes aryl or hetearyl, selected from a group comprising pyridinyl, pyrazinyl, pyrimidinyl, pyridinyl-2-one, oxadiazolyl, indazolyl, 1,3-dihydrobenzimidazol-2-one, 1,3-dihydroindol-2-one, benzotriazolyl, imidazopyridinyl, triazolepyridinyl, tetrazolepyridinyl, benzimidazolyl, 2-oxo-2,3-dihydro-1H-indol-5-yl, pyrimidin-4-one, furanyl, thiadiazolyl, pyrazolyl, isoxazolyl, pyrimidin-2,4-one, benzoxazin-3-one, 1,4-dihydrobenzoxazin-2-one, indolyl, thiophenyl, oxazolyl, benzooxazin-2-one; 3,4-dihydroquinazolin-2-one, pyridazinyl, quinoxalinyl, benzothiazolyl, benzothiadiazolyl, naphthyridinyl, cinnolinyl, 1,4-dihydroquinoxalin-2,3-dione and 1,2-dihydroindazol-3-one, where the aryl or heteroaryl is optionally substituted with 1-3 substitutes selected from a group which includes lower alkyl, hydroxy group, B(OH)₂, carboxy-lower alkoxy group, carbamoyl-lower alkoxy group, cyano group, hydroxy-lower alkyl, fluoro-lower alkyl, lower alkoxy group, halogen, S(O₂)R¹³, C(O)R¹⁴, NO₂, NR¹⁵R¹⁶, phenyl-lower alkoxy group, [1,3,4]oxadiazol-2-one, oxadiazolyl, triazolyl and isoxazolyl, imidazolyl, pyrazolyl, tetrazolyl, pyrrolyl, where imidazolyl is optionally substituted with lower alkyl, and where isoxazolyl is substituted with lower alkyl; R¹² denotes hydrogen or lower alkyl; R¹³ denotes lower alkyl, NR¹⁷R¹⁸ or fluoro-lower alkyl; R¹⁴ denotes NR¹⁹ R²⁰, lower alkoxy group, lower alkenyl-oxy group or lower alkyl; R¹⁵ and R¹⁶ independently denote hydrogen, lower alkyl, lower alkyl-carbonyl, lower alkyl-SO₂, lower alkenyl-oxycarbonyl and lower alkyl-NH-carbonyl; or NR¹⁵R¹⁶ denotes heterocyclyl selected from a group which includes morpholinyl, thiomorpholinyl, 1,1-dioxothiomorpholinyl, piperidinyl, piperidin-2-one, piperazin-2-one, 8-oxa-3-aza-bicyclo[3.2.1]octyl, piperazinyl, pyrrolidinyl, 1,1-dioxoisothiazolidinyl, pyrrolidin-2-one, imidazolidine-1,4-dione, 2,4-dihydro[1.2.4]triazol-3-one, pyrrolidine-2,5-dione, azetidin-2-one and 1,3-dihydroimidazol-2-one, where the heterocycle is optionally substituted with hydroxy-lower alkyl or lower alkyl-carbonyl; R¹⁷ and R¹⁸ independently denote hydrogen, lower alkyl, hydroxy-lower alkyl, lower alkoxy group-lower alkyl; or NR¹⁷ R¹⁸ denotes morpholinyl; R¹⁹ and R²⁰ independently denote hydrogen, lower alkyl, cycloalkyl, hydroxy-lower alkyl, lower alkoxy group-lower alkyl or cyano-lower alkyl; or NR¹⁹ R²⁰ denotes heterocyclyl selected from a group which includes morpholinyl, pyrrolidinyl, 8-oxa-3-aza-bicyclo[3.2.1]octyl, piperidinyl, piperazinyl, piperazin-2-one, thiazolidinyl, thiomorpholinyl, 1,3,8-triaza-spiro[4.5]decane-2,4-dione and spiro(1- phthalan)piperidin-4-yl, where the heterocyclyl is optionally substituted with a hydroxy group, lower alkyl-(SO₂), lower alkyl, lower alkyl-carbonyl or lower alkoxy group, carboxyl group, carbamoyl, cyano group and phenyl; and to their pharmaceutically acceptable salts. Invention also pertains to a pharmaceutical composition.

EFFECT: obtaining novel biologically active compounds which inhibit hepatic carnitine palmitoyltransferase 1 (L-CPT1).

35 cl, 565 ex, 10 tbl