HETEROAROMATIC AND AROMATIC PIPERAZINYL AZETIDINYL AMIDES AS MONOACYLGLYCEROL LIPASE INHIBITORS Russian patent published in 2015 - IPC C07D401/12 C07D401/14 C07D403/12 C07D403/14 C07D405/14 C07D409/12 C07D409/14 C07D413/12 C07D417/12 A61K31/496 A61K31/4427 A61K31/427 A61K31/506 A61P29/00 A61P25/00 

FIELD: chemistry.

SUBSTANCE: invention relates to organic chemistry and specifically to novel heterocyclic compounds of general formula (I) or enantiomers, diastereomers or pharmaceutically acceptable salts thereof, where Y is: phenyl or a heteroaryl selected from thiazolyl, pyridyl, pyrimidinyl, 1,3,5-triazinyl, benzoxazolyl, benzisoxazolyl, benzothiazolyl and 1,3,4-thiadiazolyl; wherein the phenyl or heteroaryl is optionally substituted with one substitute selected from fluorine, chlorine, bromine, iodine, C_1-4alkyl, trifluoromethyl, C_1-4alkoxy, C_1-4alkylthio, nitro and cyano; r=1-2; R² is absent or is an oxo-group; Z is: (a) phenyl substituted with NR^aR^b; where R^a is: H or C_1-4alkyl; where R^b is: C_1-4alkyl, cycloalkyl, phenyl, furanylmethyl, or phenyl(C_1-2alkyl); and wherein the phenyl or the furanyl are optionally substituted with iodine; alternatively, R^a and R^b are taken together with the nitrogen atom to which they are bonded to form a 5-8 member heterocyclyl, which is optionally condensed to a benzene ring; (b) biphenyl-3-yl or biphenyl-4-yl; where the interior phenyl ring, attached to the carbonyl in formula (I) is optionally substituted with a fluorine atom; and where the terminal phenyl ring is optionally substituted with a substitute selected from trifluoromethyl, C_1-4alkoxy, chlorine, dichloro, fluorine, and iodine; (c) phenyl substituted with a substitute selected from C_5-8cycloalkyl, -NHC(=O)cyclohexyl, phenyloxy, phenylcarbonyl, phenyl(C_1-3)alkyl, phenyl(C_1-3)alkoxy, pyrrolyl, pyrazolyl, imidazolyl, isoindol-2-yl-l,3-dione, 2,3-dihydro-isoindol-2-yl; l-(tert- butoxycarbonyl)piperidin-4-yloxy, and 1-(tert-butoxycarbonyl)piperidin-4-yl; (d) phenyl substituted with 1-2 substitutes independently selected from: C_1-6alkyl, C_1-4alkoxy, iodine, chlorine and nitro; (e) phenyl(C_1-2)alkyl; where the phenyl is optionally substituted with 1 or 2 substitutes independently selected from iodine, fluorine, C_1-6alkyl, phenyl and NR^cR^d; where R^c: H or C_1-4alkyl; where R^d is: C_1-4alkyl or C_1-6cycloalkyl(C_1-4)alkyl; and where the C_1-2alkyl of phenyl(C_1-2)alkyl is optionally substituted with phenyl; (f) phenyl(C_2-4)alkenyl; where the phenyl is optionally substituted with a substitute selected from C_1-4alkyl, C_1-4alkoxy, trifluoromethyl, trifluoromethylthio and phenyl; (g) naphthyl; where the naphthyl is optionally substituted with one C_1-4alkoxy substitute; (h) fluorenyl or xanthenyl; where the fluorenyl or xanthenyl is optionally substituted with an oxo group; (i) C_5-8cycloalkyl; where the C_5-8cycloalkyl is optionally substituted with one C_1-6alkyl substitute; (j) benzene ring-condensed C_5-8cycloalkyl or benzene ring-condensed C_5-8cycloalkyl(C_1-4)alkyl; where said C_5-8cycloalkyl fragment is optionally substituted with 1-4 methyl groups; (k) bicyclo[2.2.2]octyl-1-yl; where the bicyclo[2.2.2]octyl-l-yl is optionally substituted with C_1-6alkyl; (1) a heteroaryl or benzene ring-condensed heteroaryl selected from benzooxazolyl, quinolinyl, benzimidazolyl, pyridinyl, indolyl, thienyl, furanyl, pyrazolyl, oxazolyl, benzothienyl and benzofuranyl; where the heteroaryl or benzene ring-condensed heteroaryl is optionally substituted with 1 or 2 substitutes independently selected from C_1-4alkyl, trifluoromethyl, C_5-8cycloalkyl, phenyl, phenyl(C_1-2)alkoxy, phenyl(C_2-4)alkynyl and dichlorophenoxy; and where the phenyl substitute in the heteroaryl is further optionally substituted with C_1-4alkyl, C_1-4alkoxy or trifluoromethyl; (m) l,5-diphenyl-lH-pyrazol-3-yl; where the pyrazol-3-yl is optionally substituted with a methyl group; and where each of the phenyl groups of the 1,5-diphenyl substitutes is also optionally substituted with substitutes selected from chlorine, dichloro or aminosulphonyl; (n) 1,2,3,4-tetrahydroquinolin-6-yl; where the 1,2,3,4-tetrahydroquinolin-6-yl is optionally substituted with phenyl or trifluoromethyl-substituted phenyl; and (o) benzene ring-condensed heterocyclyl(C_2-4)alkenyl; where the benzene ring-condensed heterocyclyl is attached to the C_2-4alkenyl via the benzene ring; and where benzene ring-condensed heterocyclyl is further optionally substituted with C_5-6cycloalkyl; taking into account constraining conditions indicated in claim 1. The invention also relates to a pharmaceutical composition based on the compound of formula (I), a method of producing said pharmaceutical composition, a method of treating said pathological conditions and use of the compound of formula (I).

EFFECT: obtaining novel heterocyclic compounds having MGL inhibiting activity.

21 cl, 5 tbl, 11 ex