Compounds and compositions as gpr119 activity modulators

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of formula I:

or pharmaceutically acceptable salts thereof, in which Q is a divalent or trivalent radical selected from C6-10aryl and heteroaryl; where said aryl or heteroaryl in Q is optionally substituted up to 3 times with radicals independently selected from halogen, C1-6 alkyl, C1-6 alkyl substituted with halogen, C1-6 alkoxy group, C1-6 alkoxy group substituted with halogen, -C(O)R20 and -C(O)OR20; where R20 is selected from hydrogen and C1-6 alkyl; and where optionally, the carbon atom neighbouring W2 can be bonded through CR31 or O with a carbon atom of Q to form a 5-member ring condensed with A and Q rings; where R31 is selected from hydrogen and C1-6 alkyl; W1 and W2 are independently selected from CR21 and N; where R21 is selected from hydrogen and -C(O)OR25; where R25 denotes hydrogen; ring A can contain up to 2 carbon ring atoms substituted with a group selected from -C(O)-, -C(S)- and -C(=NOR30)- and can be partially unsaturated and contain up to 2 double bonds; where R30 denotes hydrogen ; L is selected from C1-6alkylene, C2-6alkenylene, -OC(O)(CH2)n-, -NR26(CH2)n- and -O(CH2)n-; where R26 is selected from hydrogen and C1-6 alkyl; where n is selected from 0, 1, 2, 3 and 4; q is selected from 0 and 1; t1, t2, t3 and t4 are each independently selected from 0, 1 and 2; R1 is selected from -X1S(O)0-2X2R6a, -X1S(O)0-2X2OR6a, -X1S(O)0-2X2C(O)R6a, -X1S(O)0-2X2C(O)OR6a, -X1S(O)0-2X2OC(O)R6a and -X1S(O)0-2NR6aR6b; where X1 is selected from a bond, O, NR7a and C1-4alkylene; where R7a is selected from hydrogen and C1-6alkyl; X2 is selected from a bond and C1-6alkylene; R6a is selected from hydrogen, cyanogroup, halogen, C1-6alkyl, C2-6alkenyl, C6-10aryl, heteroaryl, heterocycloalkyl and C3-8cycloalkyl; where said aryl, heteroaryl, cycloalkyl and heterocycloalkyl in R6a is optionally substituted with 1-3 radicals independently selected from hydroxy group, halogen, C1-6alkyl, C1-6alkyl substituted with a cyano group, C1-6alkoxy group and C6-10aryl-C1-4alkoxy group; and R6b is selected from hydrogen and C1-6alkyl; R3 is selected from hydrogen, halogen, hydroxy group, C1-6alkyl, C1-6alkyl substituted with halogen, C1-6alkyl substituted with a hydroxy group, C1-6alkoxy group, C1-6alkoxy group substituted with halogen, -C(O)R23 and -C(O)OR23; where R23 is selected from hydrogen and C1-6alkyl; R4 is selected from R8 and -C(O)OR8; where R8 is selected from C1-6alkyl, heteroaryl, C3-8cycloalkyl and heterocycloalkyl; where said heteroaryl, cycloalkyl or heterocycloalkyl in R8 is optionally substituted with 1-3 radicals independently selected from halogen, C1-6alkyl, C3-8cycloalkyl and C1-6alkyl substituted with halogen; R5 is selected from hydrogen, C1-6alkyl substituted with a hydroxy group, and a C1-6alkoxy group; heteroaryl denotes a monocyclic or condensed bicyclic aromatic ring complex containing 5-9 carbon atoms in the ring, where one or more ring members are heteroatoms selected from nitrogen, oxygen and sulphur, and heterocycloalkyl denotes a saturated monocyclic 4-6-member ring in which one or more said carbon atoms in the ring are substituted with a group selected from -O-, -S- and -NR-, where R denotes a bond, hydrogen or C1-6alkyl. The invention also relates to pharmaceutical compositions containing said compounds, and methods of using said compounds to treat or prevent diseases or disorders associated with GPR119 activity, such as obesity, type 1 diabetes, type 2 sugar diabetes, hyperlipidemia, type 1 autopathic diabetes, latent autoimmune diabetes in adults, type 2 early diabetes, child atypical diabetes, adult diabetes in children, malnutrition-associated diabetes and diabetes in pregnant women.

EFFECT: improved properties of compounds.

27 cl

 

The text descriptions are given in facsimile form.

1. The compound of the formula I

or its pharmaceutically acceptable salt,
in which
Q is a divalent or trivalent radical,
selected from C6-10aryl and heteroaryl;
DG is specified aryl or heteroaryl in Q is optionally substituted up to 3 times by radicals, independently selected from halogen, C1-6of alkyl, C1-6of alkyl, substituted with halogen, C1-6alkoxygroup,1-6alkoxygroup substituted with halogen, -C(O)R20and-C(O)OR20; where R20selected from hydrogen and C1-6of alkyl; and
where optional carbon atom adjacent to W2can be connected through CR31or with the carbon atom of Q, with the formation of 5-membered ring fused with the ring a and Q; where R31selected from hydrogen and C1-6of alkyl;
W1and W2independently selected from CR21and N; where R21selected from hydrogen and-C(O)OR25; where R25represents hydrogen;
the ring And may contain up to 2 ring carbon atoms, substituted by a group selected from-C(O)-, -C(S)- and-C(=NOR30), and may be partially unsaturated, containing up to 2 double bonds; R30represents hydrogen;
L is selected from C1-6alkylene,2-6Alcanena, -OC(O)(CH2)n-, -NR26(CH2)nand
-O(CH2)n-;
where R26selected from hydrogen and C1-6of alkyl;
where n is selected from 0, 1, 2, 3, and 4;
q is selected from 0 and 1;
t1t2, t3and t4each independently selected from 0, 1 and 2;
R1selected from-X1S(O)0-2X2R6a, -X1S(O)0-2X2OR6a, -X1S(O)0-2X2C(O)R6a,
-X1 S(O)0-2X2C(O)OR6a, -X1S(O)0-2X2OC(O)R6aand-X1S(O)0-2NR6aR6b;
where X1selected from Oh, NR7aand C1-4alkylene; where R7aselected from hydrogen and C1-6of alkyl;
X2selected from communication and1-4alkylene;
R6aselected from hydrogen, ceanography, halogen, C1-6of alkyl, C2-6alkenyl,6-10aryl, heteroaryl, geterotsiklicheskie and C3-8cycloalkyl; where specified aryl, heteroaryl, cycloalkyl and heteroseksualci R6aoptionally substituted by 1-3 radicals independently selected from hydroxy-group, halogen, C1-6of alkyl, C1-6of alkyl, substituted by cyano, C1-6alkoxygroup and C6-10aryl-C1-4alkoxygroup; and R6bselected from hydrogen and C1-6of alkyl;
R3selected from hydrogen, halogen, hydroxy-group, With1-6of alkyl, C1-6of alkyl, substituted with halogen, C1-6of alkyl, substituted hydroxy-group, C1-6alkoxygroup,1-6alkoxygroup, substituted with halogen, -C(O)R23and-C(O)OR23; where R23selected from hydrogen and C1-6of alkyl;
R4selected from R8and-C(O)OR8; where R8selected from C1-6of alkyl, heteroaryl,3-8cycloalkyl and geterotsiklicheskie; where the specified heteroaryl, cycloalkyl or heteroseksualci R8it is certainly substituted by 1-3 radicals, independently selected from halogen, C1-6of alkyl, C3-8cycloalkyl and C1-6of alkyl, substituted with halogen;
R5selected from hydrogen, C1-6of alkyl, substituted hydroxy-group, and C1-6alkoxygroup;
heteroaryl means a monocyclic or condensed bicyclic aromatic ring complex containing 5 to 9 carbon atoms in the ring, where one or more ring members are heteroatoms selected from nitrogen, oxygen and sulfur, and heteroseksualci means a saturated monocyclic 4-6-membered ring in which one or more of the carbon atoms in ring substituted by a group selected from-O-, -S - and-NR-, where R is a bond, hydrogen or C1-6alkyl.

2. The compound according to claim 1 of formula Ia

in which
Q is a divalent radical selected from C6-10aryl and heteroaryl; where specified aryl or heteroaryl in Q is optionally substituted up to 3 times by radicals independently selected from halogen, C1-6of alkyl, C1-6of alkyl, substituted with halogen, C1-6alkoxygroup, C1-6alkoxygroup, substituted with halogen, -C(O)R20and-C(O)OR20; where R20selected from hydrogen and C1-6of alkyl; and
the ring And may contain up to 2 ring carbon atoms, substituted by a group selected from-C(O)- -C(S)- and-C(=NOR 30)-.

3. The compound according to claim 1 of formula Ia'

in which
Q is a divalent radical selected from C6-10aryl and heteroaryl; where specified aryl or heteroaryl in Q is optionally substituted up to 3 times by radicals independently selected from halogen, C1-6of alkyl, C1-6of alkyl, substituted with halogen, C1-6alkoxygroup, C1-6alkoxygroup, substituted with halogen, -C(O)R20and-C(O)OR20; where R20selected from hydrogen and C1-6of alkyl; and
the ring And may contain up to 2 ring carbon atoms, substituted by a group selected from-C(O)-, -C(S)- and-C(=NOR30)-, where R30selected from hydrogen and C1-6the alkyl.

4. The compound according to any one of claims 1 to 3, in which Q is selected from phenyl, pyridinyl, pyrazinyl, pyridazinyl, pyrimidinyl, 1,2,4-oxadiazolyl and thiazolyl; where specified phenyl, pyridinyl, pyrazinyl, pyridazinyl, pyrimidinyl and thiazolyl in Q is optionally substituted up to 3 times by radicals independently selected from halogen, C1-6of alkyl, C1-6alkoxygroup,1-6of alkyl, substituted with halogen, -C(O)OR20and-C(O)R20;
where R20selected from hydrogen and C1-6the alkyl.

5. The compound according to any one of claims 1 to 4, in which L is selected from-O(CH2)0-4-,
-(CH=CH)-, -OC(O)-, -NH(CH2)0-4-, -NCH3(CH2)0-4- and -(CH 2)1-4-.

6. The compound according to any one of claims 1 to 5, in which R1selected from-S(O)0-2X2R6a,
-S(O)0-2X2OR6a, -S(O)0-2X2C(O)OR6a, -S(O)0-2X2OC(O)R6aand-S(O)0-2NR6aR6b;
where X2selected from communication and1-4alkylene;
R6aselected from hydrogen, halogen, ceanography, methyl, ethyl, propyl, isopropyl, Attila, pyridinyl, pyrrolidinyl, piperidinyl, morpholino, isoxazolyl, tetrazolyl, phenyl and imidazolyl; where the specified piperidinyl, pyridinyl, pyrrolidinyl, morpholino, isoxazolyl, tetrazolyl, phenyl or imidazolyl R6aoptionally substituted by 1-3 radicals independently selected from hydroxy-group, halogen, C1-6the alkyl and benthochromis; and R6bselected from hydrogen, methyl and ethyl.

7. The compound according to any one of claims 1 to 5, in which
R4selected from R8and-C(O)OR8;
where R8selected from isopropyl, cyclopropyl, tert-butyl, 1,2,4-oxadiazolyl, pyrimidinyl, pyridinyl, pyridazinyl, tetrahydro-2H-pyranyl, tetrahydrofuranyl, oxetanyl 2N-tetrazolyl and thiazolyl;
where specified cyclopropyl, 1,2,4-oxadiazolyl, pyrimidinyl, pyridinyl, pyridazinyl, tetrahydro-2H-pyranyl, tetrahydrofuranyl, oxetanyl 2N-tetrazolyl or thiazolyl R8optionally substituted by 1-3 radicals independently selected and from halogen, trifloromethyl, isopropyl, tert-butyl, methyl, ethyl and cyclopropyl, optionally substituted stands; and
R5selected from hydrogen and metoxygroup.

8. The compound according to claim 1, selected from the following compounds:
1-methylcyclopropyl 4-((5-(4-(methylsulphonyl)piperazine-1-yl)pyrazin-2-yloxy)methyl)piperidine-1-carboxylate,
isopropyl 4-((4-((4-methanesulfonylaminoethyl)-1-yl)phenoxy)methyl)piperidine-1-carboxylate,
isopropyl 4-(2-(4-(4-(methylsulphonyl)piperazine-1-yl)phenoxy)ethyl)piperidine-1-carboxylate,
isopropyl 4-(3-(4-(4-(methylsulphonyl)piperazine-1-yl)phenoxy)propyl)piperidine-1-carboxylate,
isopropyl 4-(4-(4-(4-(methylsulphonyl)piperazine-1-yl)phenoxy)butyl)piperidine-1-carboxylate,
isopropyl 4-((6-(4-(methylsulphonyl)piperazine-1-yl)pyridine-3-yloxy)methyl)piperidine-1-carboxylate,
tert-butyl 4-((6-(4-(methylsulphonyl)piperazine-1-yl)pyridine-3-yloxy)methyl)piperidine-1-carboxylate,
isopropyl 4-((5-(4-(methylsulphonyl)piperazine-1-yl)pyrazin-2-yloxy)methyl)piperidine-1-carboxylate,
tert-butyl 4-((5-(4-(methylsulphonyl)piperazine-1-yl)pyrazin-2-yloxy)methyl)piperidine-1-carboxylate,
3-cyclopropyl-5-(4-((5-(4-(methylsulphonyl)piperazine-1-yl)pyrazin-2-yloxy)methyl)piperidine-1-yl)-1,2,4-oxadiazol,
5-cyclopropyl-3-(4-((5-(4-(methylsulphonyl)piperazine-1-yl)pyrazin-2-yloxy)methyl)piperidine-1-yl)-1,2,4-oxadiazol,
2-(4-(methylsulphonyl)piperazine-1-yl)-5-((1-(5-(Tr is permitil)pyridine-2-yl)piperidine-4-yl)methoxy)pyrazin,
5-isopropyl-3-(4-((5-(4-(methylsulphonyl)piperazine-1-yl)pyrazin-2-yloxy)methyl)piperidine-1-yl)-1,2,4-oxadiazol,
tetrahydro-2H-Piran-4-yl 4-((5-(4-(methylsulphonyl)piperazine-1-yl)pyrazin-2-yloxy)methyl)piperidine-1-carboxylate,
(S)-tetrahydrofuran-3-yl 4-((5-(4-(methylsulphonyl)piperazine-1-yl)pyrazin-2-yloxy)methyl)piperidine-1-carboxylate,
(R)-tetrahydrofuran-3-yl 4-((5-(4-(methylsulphonyl)piperazine-1-yl)pyrazin-2-yloxy)methyl)piperidine-1-carboxylate,
2-isopropyl-5-(4-((5-(4-(methylsulphonyl)piperazine-1-yl)pyrazin-2-yloxy)methyl)piperidine-1-yl)thiazole,
2-((1-(2-methyl-2H-tetrazol-5-yl)piperidine-4-yl)methoxy)-5-(4-(methylsulphonyl)piperazine-1-yl)pyrazin,
oxetan-3-yl 4-((5-(4-(methylsulphonyl)piperazine-1-yl)pyrazin-2-yloxy)methyl)piperidine-1-carboxylate,
isopropyl 4-((5-(4-(methylsulphonyl)piperazine-1-yl)pyridine-2-yloxy)methyl)piperidine-1-carboxylate,
isopropyl 4-((6-(4-(methylsulphonyl)piperazine-1-yl)pyridazin-3-yloxy)methyl)piperidine-1-carboxylate,
isopropyl 4-((5-(4-(methylsulphonyl)piperazine-1-yl)pyrimidine-2-yloxy)methyl)piperidine-1-carboxylate,
(E)-isopropyl 4-(2-(6-(4-(methylsulphonyl)piperazine-1-yl)pyridine-3-yl)vinyl)piperidine-1-carboxylate,
isopropyl 4-(2-(6-(4-(methylsulphonyl)piperazine-1-yl)pyridine-3-yl)ethyl)piperidine-1-carboxylate,
(E)-isopropyl 4-(2-(2-(4-(methylsulphonyl)piperazine-1-yl)pyrimidine-5-yl)vinyl)piperidine-1-carboxylate,
5-ethyl-2-(4-((6-(4-(methyls Lionel)piperazine-1-yl)pyridine-3-yloxy)methyl)piperidine-1-yl)pyrimidine,
1-(methylsulphonyl)-4-(5-((1-(5-(trifluoromethyl)pyridin-2-yl)piperidine-4-yl)methoxy)pyridin-2-yl)piperazine,
5-ethyl-2-(4-((5-(4-(methylsulphonyl)piperazine-1-yl)pyrazin-2-yloxy)methyl)piperidine-1-yl)pyrimidine,
2-((1-(5-methylpyridin-2-yl)piperidine-4-yl)methoxy)-5-(4-(methylsulphonyl)piperazine-1-yl)pyrazin,
1-methylcyclopropyl 4-((5-(4-(methylsulphonyl)piperazine-1-yl)pyridine-2-yloxy)methyl)piperidine-1-carboxylate,
5-ethyl-2-(4-((5-(4-(methylsulphonyl)piperazine-1-yl)pyridine-2-yloxy)methyl)piperidine-1-yl)pyrimidine,
3-isopropyl-5-(4-((5-(4-(methylsulphonyl)piperazine-1-yl)pyrazin-2-yloxy)methyl)piperidine-1-yl)-1,2,4-oxadiazol,
3-isopropyl-5-(4-((5-(4-(methylsulphonyl)piperazine-1-yl)pyridine-2-yloxy)methyl)piperidine-1-yl)-1,2,4-oxadiazol,
1-methylcyclopropyl 4-((6-(4-(methylsulphonyl)piperazine-1-yl)pyridine-3-yloxy)methyl)piperidine-1-carboxylate,
5-isopropyl-3-(4-((6-(4-(methylsulphonyl)piperazine-1-yl)pyridine-3-yloxy)methyl)piperidine-1-yl)-1,2,4-oxadiazol,
2-((1-(5-herperidin-2-yl)piperidine-4-yl)methoxy)-5-(4-(methylsulphonyl)piperazine-1-yl)pyrazin,
3-isopropyl-5-(4-((6-(4-(methylsulphonyl)piperazine-1-yl)pyridine-3-yloxy)methyl)piperidine-1-yl)-1,2,4-oxadiazol,
tert-butyl 4-((5-(4-(methylsulphonyl)-1,4-diazepan-1-yl)pyrazin-2-yloxy)methyl)piperidine-1-carboxylate,
tert-butyl 4-((5-(4-(methylsulphonyl)-1,4-diazepan-1-yl)pyrazin-2-yloxy)methyl)piperidine-1-carboxylate,
tert-butyl 4-((5-(4-(matilal is of IMT)piperidine-1-yl)pyrazin-2-yloxy)methyl)piperidine-1-carboxylate,
1-methylcyclopropyl 4-((5-(4-(methylsulphonyl)piperidine-1-yl)pyrazin-2-yloxy)methyl)piperidine-1-carboxylate,
tert-butyl 4-(2-(3-(4-(methylsulphonyl)piperazine-1-yl)-1,2,4-oxadiazol-5-yl)ethyl)piperidine-1-carboxylate,
tert-butyl 4-(3-(3-(4-(methylsulphonyl)piperazine-1-yl)-1,2,4-oxadiazol-5-yl)propyl)piperidine-1-carboxylate,
5-(3-(1-(5-ethylpyrimidine-2-yl)piperidine-4-yl)propyl)-3-(4-(methylsulphonyl)piperazine-1-yl)-1,2,4-oxadiazol,
isopropyl 4-(3-(3-(4-(methylsulphonyl)piperazine-1-yl)-1,2,4-oxadiazol-5-yl)propyl)piperidine-1-carboxylate,
3-isopropyl-5-(4-(2-(5-(4-(methylsulphonyl)piperazine-1-yl)thiazol-2-yl)ethyl)piperidine-1-yl)-1,2,4-oxadiazol,
isopropyl 4-((4-(1-methanesulfonyl-1,2,3,6-tetrahydropyridine-4-yl)phenoxy)methyl)piperidine-1-carboxylate,
isopropyl 4-(4-(1-(methylsulphonyl)-1,2,3,6-tetrahydropyridine-4-yl)phenoxy)piperidine-1-carboxylate,
isopropyl 4-(2-(4-(1-(methylsulphonyl)-1,2,3,6-tetrahydropyridine-4-yl)phenoxy)ethyl)piperidine-1-carboxylate,
isopropyl 4-(3-(4-(1-(methylsulphonyl)-1,2,3,6-tetrahydropyridine-4-yl)phenoxy)propyl)piperidine-1-carboxylate,
isopropyl 4-(4-(4-(1-(methylsulphonyl)-1,2,3,6-tetrahydropyridine-4-yl)phenoxy)butyl)piperidine-1-carboxylate,
1-methylcyclopropyl 4-((4-(1-(methylsulphonyl)-1,2,3,6-tetrahydropyridine-4-yl)phenoxy)methyl)piperidine-1-carboxylate,
5-isopropyl-3-(4-((4-(1-(methylsulphonyl)-1,2,3,6-tetrahydropyridine-4-yl)phenoxy)methyl)piperidine-1-yl)-1,2,4-ACS is diazol,
isopropyl 4-(3-(3-(1-(methylsulphonyl)-1,2,3,6-tetrahydropyridine-4-yl)phenoxy)propyl)piperidine-1-carboxylate,
isopropyl 4-((4-(1-methanesulfonamido-4-yl)phenoxy)methyl)piperidine-1-carboxylate,
isopropyl 4-(4-(1-(methylsulphonyl)piperidine-4-yl)phenoxy)piperidine-1-carboxylate,
isopropyl 4-(2-(4-(1-(methylsulphonyl)piperidine-4-yl)phenoxy)ethyl)piperidine-1-carboxylate,
isopropyl 4-(3-(4-(1-(methylsulphonyl)piperidine-4-yl)phenoxy)propyl)piperidine-1-carboxylate,
isopropyl 4-(4-(4-(1-(methylsulphonyl)piperidine-4-yl)phenoxy)butyl)piperidine-1-carboxylate,
1-methylcyclopropyl 4-((4-(1-(methylsulphonyl)piperidine-4-yl)phenoxy)methyl)piperidine-1-carboxylate,
2-(4-((4-(1-(methylsulphonyl)piperidine-4-yl)phenoxy)methyl)piperidine-1-yl)-5-(trifluoromethyl)pyridine,
2-(4-((4-(1-(methylsulphonyl)piperidine-4-yl)phenoxy)methyl)piperidine-1-yl)-5-(trifluoromethyl)pyridine,
5-isopropyl-3-(4-((4-(1-(methylsulphonyl)piperidine-4-yl)phenoxy)methyl)piperidine-1-yl)-1,2,4-oxadiazol,
3-chloro-2-(4-((4-(1-(methylsulphonyl)piperidine-4-yl)phenoxy)methyl)piperidine-1-yl)-5-(trifluoromethyl)pyridine,
5-chloro-2-(4-((4-(1-(methylsulphonyl)piperidine-4-yl)phenoxy)methyl)piperidine-1-yl)pyridine,
3-chloro-6-(4-((4-(1-(methylsulphonyl)piperidine-4-yl)phenoxy)methyl)piperidine-1-yl)pyridazin,
5-bromo-2-(4-((4-(1-(methylsulphonyl)piperidine-4-yl)phenoxy)methyl)piperidine-1-yl)pyrimidine,
5-ethyl-2-(4-((4-(1-(methylsulphonyl)piperidine-4-yl)f is noxi)methyl)piperidine-1-yl)pyrimidine,
5-fluoro-2-(4-((4-(1-(methylsulphonyl)piperidine-4-yl)phenoxy)methyl)piperidine-1-yl)pyridine,
3-isopropyl-5-(4-((4-(1-(methylsulphonyl)piperidine-4-yl)phenoxy)methyl)piperidine-1-yl)-1,2,4-oxadiazol,
3-tert-butyl-6-(4-((4-(1-(methylsulphonyl)piperidine-4-yl)phenoxy)methyl)piperidine-1-yl)pyridazin,
5-fluoro-2-(4-((4-(1-(methylsulphonyl)piperidine-4-yl)phenoxy)methyl)piperidine-1-yl)pyrimidine,
2-(4-((2-bromo-4-(1-(methylsulphonyl)piperidine-4-yl)phenoxy)methyl)piperidine-1-yl)-5-ftorpirimidinu,
isopropyl 4-(2-(3-(1-methanesulfonyl-1,2,3,6-tetrahydropyridine-4-yl)phenoxy)ethyl)piperidine-1-carboxylate,
1-methylcyclopropyl 4-methoxy-4-((5-(4-(methylsulphonyl)piperazine-1-yl)pyrazin-2-yloxy)methyl)piperidine-1-carboxylate,
1-methylcyclopropyl 4-((6-formyl-5-(4-(methylsulphonyl)piperazine-1-yl)pyrazin-2-yloxy)methyl)piperidine-1-carboxylate,
1-methylcyclopropyl 4-((6-chloro-5-(4-(methylsulphonyl)piperazine-1-yl)pyrazin-2-yloxy)methyl)piperidine-1-carboxylate,
1-methylcyclopropyl 4-((5-(4-(3-methoxy-3-oxopropylidene)piperazine-1-yl)pyrazin-2-yloxy)methyl)piperidine-1-carboxylate,
1-methylcyclopropyl 4-(((5-(4-((3,5-dimethylisoxazol-4-yl)sulfonyl)piperazine-1-yl)pyrazin-2-yloxy)methyl)piperidine-1-carboxylate,
1-methylcyclopropyl 4-(((5-(4-((4-(benzyloxy)phenyl)sulfonyl)piperazine-1-yl)pyrazin-2-yloxy)methyl)piperidine-1-carboxylate,
3-(4-(5-((1-((1-methylcyclopropene)carbonyl)piperidine-4-yl)methoxy)the feast of the Zin-2-yl)piperazine-1-ylsulphonyl)propanoic acid,
1-methylcyclopropyl 4-(((5-(4-((3-hydroxypropyl)sulfonyl)piperazine-1-yl)pyrazin-2-yl)oxy)methyl)piperidine-1-carboxylate;
1-methylcyclopropyl 4-(((5-(4-((4-hydroxyphenyl)sulfonyl)piperazine-1-yl)pyrazin-2-yl)oxy)methyl)piperidine-1-carboxylate;
1-methylcyclopropyl 4-((5-(4-(3-cyanopropionic)piperazine-1-yl)pyrazin-2-yloxy)methyl)piperidine-1-carboxylate;
1-methylcyclopropyl 4-((5-(4-(3-(1H-tetrazol-5-yl)propylsulfonyl)piperazine-1-yl)pyrazin-2-yloxy)methyl)piperidine-1-carboxylate;
1-methylcyclopropyl 4-((5-(4-(vinylsulphonyl)piperazine-1-yl)pyrazin-2-yloxy)methyl)piperidine-1-carboxylate;
1-methylcyclopropyl 4-((5-(4-(2-(piperidine-1-yl)ethylsulfonyl)piperazine-1-yl)pyrazin-2-yloxy)methyl)piperidine-1-carboxylate;
1-methylcyclopropyl 4-((5-(4-(2-morpholinoethyl)piperazine-1-yl)pyrazin-2-yloxy)methyl)piperidine-1-carboxylate;
tert-butyl 4-((5-(4-(3-chloropropanesulfonyl)piperazine-1-yl)pyrazin-2-yloxy)methyl)piperidine-1-carboxylate;
tert-butyl 4-((5-(4-(3-acetoxypropionyl)piperazine-1-yl)pyrazin-2-yloxy)methyl)piperidine-1-carboxylate;
1-methylcyclopropyl 4-((5-(4-(2-amoxicillini)piperazine-1-yl)pyrazin-2-yloxy)methyl)piperidine-1-carboxylate;
1-methylcyclopropyl 4-((5-(4-(3-(pyrrolidin-1-yl)propylsulfonyl)piperazine-1-yl)pyrazin-2-yloxy)methyl)piperidine-1-carboxylate;
1-methylcyclopropyl 4-((5-(4-(3-(2-methyl-1H-imidazol-1-yl)propelant the Nile)piperazine-1-yl)pyrazin-2-yloxy)methyl)piperidine-1-carboxylate;
tert-butyl 4-(((5-(4-((3-chlorpropyl)sulfonyl)piperazine-1-yl)pyrazin-2-yl)oxy)methyl)piperidine-1-carboxylate;
1-methylcyclopropyl 4-(((5-(4-((3-chlorpropyl)sulfonyl)piperazine-1-yl)pyrazin-2-yl)oxy)methyl)piperidine-1-carboxylate;
1-methylcyclopropyl 4-((5-(4-(propylsulfonyl)piperazine-1-yl)pyrazin-2-yloxy)methyl)piperidine-1-carboxylate;
1-methylcyclopropyl 4-((5-(4-(ethylsulfonyl)piperazine-1-yl)pyrazin-2-yloxy)methyl)piperidine-1-carboxylate;
1-methylcyclopropyl 4-((5-(4-(isopropylphenyl)piperazine-1-yl)pyrazin-2-yloxy)methyl)piperidine-1-carboxylate;
1-methylcyclopropyl 4-((5-(4-(isobutylphenyl)piperazine-1-yl)pyrazin-2-yloxy)methyl)piperidine-1-carboxylate;
1-methylcyclopropyl 4-((5-(4-(second-butylsulfonyl)piperazine-1-yl)pyrazin-2-yloxy)methyl)piperidine-1-carboxylate;
1-methylcyclopropyl 4-((5-(4-(2-(pyridin-3-yl)ethylsulfonyl)piperazine-1-yl)pyrazin-2-yloxy)methyl)piperidine-1-carboxylate;
1-methylcyclopropyl 4-((5-(4-(2-(pyridin-4-yl)ethylsulfonyl)piperazine-1-yl)pyrazin-2-yloxy)methyl)piperidine-1-carboxylate;
1-methylcyclopropyl 4-((5-(4-sulfamoylbenzoic-1-yl)pyrazin-2-yloxy)methyl)piperidine-1-carboxylate;
tert-butyl 4-((5-(4-(morpholinomethyl)piperazine-1-yl)pyrazin-2-yloxy)methyl)piperidine-1-carboxylate;
1-methylcyclopropyl 4-((6-(4-(ethylsulfonyl)piperazine-1-yl)pyridine-3-yloxy)methyl)piperidine-1-carboxylate;
1-methylcyclopropyl -((5-fluoro-6-(4-(methylsulphonyl)piperazine-1-yl)pyridine-3-yloxy)methyl)piperidine-1-carboxylate;
tert-butyl 4-((5-(4-(methylsulphonyl)-2-oxopiperidin-1-yl)pyrazin-2-yloxy)methyl)piperidine-1-carboxylate;
1-methylcyclopropyl 4-((5-(4-(methylsulphonyl)-2-oxopiperidin-1-yl)pyrazin-2-yloxy)methyl)piperidine-1-carboxylate;
1-methylcyclopropyl 4-((5-(2-oxo-4-(propylsulfonyl)piperazine-1-yl)pyrazin-2-yloxy)methyl)piperidine-1-carboxylate;
1-methylcyclopropyl 4-((5-(4-(isopropylphenyl)-2-oxopiperidin-1-yl)pyrazin-2-yloxy)methyl)piperidine-1-carboxylate;
1-methylcyclopropyl 4-(((6-(4-(methylsulphonyl)-2-oxopiperidin-1-yl)pyridine-3-yl)oxy)methyl)piperidine-1-carboxylate;
1-methylcyclopropyl 4-((6-(2-oxo-4-(propylsulfonyl)piperazine-1-yl)pyridine-3-yloxy)methyl)piperidine-1-carboxylate;
1-methylcyclopropyl 4-((6-(4-(isopropylphenyl)-2-oxopiperidin-1-yl)pyridine-3-yloxy)methyl)piperidine-1-carboxylate;
1-(5-((1-(5-ethylpyrimidine-2-yl)piperidine-4-yl)methoxy)pyrazin-2-yl)-4-(methylsulphonyl)piperazine-2-he;
1-(5-((1-(5-ethylpyrimidine-2-yl)piperidine-4-yl)methoxy)pyridin-2-yl)-4-(methylsulphonyl)piperazine-2-he;
tert-butyl 4-((2,6-debtor-4-(1-(methylsulphonyl)piperidine-4-yl)phenoxy)methyl)piperidine-1-carboxylate;
tert-butyl 4-((2-methyl-4-(1-(methylsulphonyl)piperidine-4-yl)phenoxy)methyl)piperidine-1-carboxylate;
tert-butyl 4-((3-methoxy-4-(1-(methylsulphonyl)piperidine-4-yl)phenoxy)methyl)piperidine-1-carboxylate;
tert-butyl 4-((2,6-dimethyl-4-(1-(methylsulphonyl)piperidin the-4-yl)phenoxy)methyl)piperidine-1-carboxylate;
tert-butyl 4-((2,5-dimethyl-4-(1-(methylsulphonyl)piperidine-4-yl)phenoxy)methyl)piperidine-1-carboxylate;
tert-butyl 4-((2-(methoxycarbonyl)-4-(1-(methylsulphonyl)piperidine-4-yl)phenoxy)methyl)piperidine-1-carboxylate;
tert-butyl 4-((2-chloro-4-(1-(methylsulphonyl)piperidine-4-yl)phenoxy)methyl)piperidine-1-carboxylate;
tert-butyl 4-((3-methyl-4-(1-(methylsulphonyl)piperidine-4-yl)phenoxy)methyl)piperidine-1-carboxylate;
tert-butyl 4-((2,3-dimethyl-4-(1-(methylsulphonyl)piperidine-4-yl)phenoxy)methyl)piperidine-1-carboxylate;
tert-butyl 4-((2-fluoro-4-(1-(methylsulphonyl)piperidine-4-yl)phenoxy)methyl)piperidine-1-carboxylate;
tert-butyl 4-((4-(1-(methylsulphonyl)piperidine-4-yl)-2-(trifluoromethyl)phenoxy)methyl)piperidine-1-carboxylate;
2-(4-((2,6-debtor-4-(1-(methylsulphonyl)piperidine-4-yl)phenoxy)methyl)piperidine-1-yl)-5-ethylpyrimidine;
1-methylcyclopropyl 4-((2,6-debtor-4-(1-(methylsulphonyl)piperidine-4-yl)phenoxy)methyl)piperidine-1-carboxylate;
3-(4-(4-((1-(5-ethylpyrimidine-2-yl)piperidine-4-yl)methoxy)for 3,5-differenl)piperidine-1-ylsulphonyl)propyl;
1-methylcyclopropyl 4-((4-(1-(3-acetoxypropionyl)piperidine-4-yl)-2,6-divergence)methyl)piperidine-1-carboxylate;
3-(4-(4-((1-(5-ethylpyrimidine-2-yl)piperidine-4-yl)methoxy)for 3,5-differenl)piperidine-1-ylsulphonyl)propan-1-ol;
1-methylcyclopropyl 4-((2,6-debtor-4-(1-(3-hydroxypropanesulfonic)piperidine-4-yl)phenoxy)methyl)PIP is ridin-1-carboxylate;
isopropyl 4-((5-(1,2,3,6-tetrahydro-1-methanesulfonamido-4-yl)pyrazin-2-yloxy)methyl)piperidine-1-carboxylate;
1-methylcyclopropyl 4-((6-(1,2,3,6-tetrahydro-1-methanesulfonamido-4-yl)pyridine-3-yloxy)methyl)piperidine-1-carboxylate;
isopropyl 4-(2-(6-(1,2,3,6-tetrahydro-1-methanesulfonamido-4-yl)pyridine-3-yloxy)ethyl)piperidine-1-carboxylate;
2-(4-((5-(1,2,3,6-tetrahydro-1-methanesulfonamido-4-yl)pyrazin-2-yloxy)methyl)piperidine-1-yl)-5-ethylpyrimidine;
2-(4-((6-(1,2,3,6-tetrahydro-1-methanesulfonamido-4-yl)pyridine-3-yloxy)methyl)piperidine-1-yl)-5-ethylpyrimidine;
2-((1-(5-ethylpyrimidine-2-yl)piperidine-4-yl)methoxy)-5-(1-methanesulfonamido-4-yl)pyrazin;
2-(4-((6-(1-methanesulfonamido-4-yl)pyridine-3-yloxy)methyl)piperidine-1-yl)-5-ethylpyrimidine;
3-((1-(5-ethylpyrimidine-2-yl)piperidine-4-yl)methoxy)-6-(1-methanesulfonamido-4-yl)pyridazin;
2-(4-((5-(1-methanesulfonamido-4-yl)pyridine-2-yloxy)methyl)piperidine-1-yl)-5-ethylpyrimidine;
1-tert-butyl 4-(4-(1-(methylsulphonyl)piperidine-4-yl)phenyl)piperazine-1,4 -, in primary forms;
N-((1-(5-ethylpyrimidine-2-yl)piperidine-4-yl)methyl)-4-(1-(methylsulphonyl)piperidine-4-yl)aniline;
N-((1-(5-ethylpyrimidine-2-yl)piperidine-4-yl)methyl)-M-methyl-4-(1-(methylsulphonyl)piperidine-4-yl)aniline;
4-(4-((1-(5-ftorpirimidinu-2-yl)piperidine-4-yl)methoxy)phenyl)-1-(methylsulphonyl)piperidine-4-carboxylic acid;
1-methylcyclopropyl 4-({[5(2-oxo-4-{[2-(pyrrolidin-1-yl)ethane]sulfonyl}piperazine-1-yl)pyrazin-2-yl]oxy}methyl)piperidine-1-carboxylate;
1-methylcyclopropyl 4-({[5-(4-{[2-(morpholine-4-yl)ethane]sulfonyl}-2-oxopiperidin-1-yl)pyrazin-2-yl]oxy}methyl)piperidine-1-carboxylate;
1-methylcyclopropyl 4-({[5-(4-{[2-(1,3-dioxo-2,3-dihydro-1H-isoindole-2-yl)ethane]sulfonyl}-2-oxopiperidin-1-yl)pyrazin-2-yl]oxy}methyl)piperidine-1-carboxylate;
1-methylcyclopropyl 4-{[(5-{4-[1-(2-methylpropyl " pyrrolidin-3-sulfonyl]-2-oxopiperidin-1-yl}pyrazin-2-yl)oxy]methyl}piperidine-1-carboxylate;
1-methylcyclopropyl 4-({[5-(2-oxo-4-{[3-(1H-pyrazole-1-yl)propane]sulfonyl}piperazine-1-yl)pyrazin-2-yl]oxy}methyl)piperidine-1-carboxylate;
1-methylcyclopropyl 4-[({5-[2-oxo-4-(pyrrolidin-3-sulfonyl)piperazine-1-yl]pyrazin-2-yl}oxy)methyl]piperidine-1-carboxylate;
1-methylcyclopropyl 4-({[5-(4-{[(1-methylpyrrolidine-3-yl)methane]sulfonyl}-2-oxopiperidin-1-yl)pyrazin-2-yl]oxy}methyl)piperidine-1-carboxylate;
1-methylcyclopropyl 4-({[5-(4-{[2-(azetidin-1-yl)ethane]sulfonyl}-2-oxopiperidin-1-yl)pyrazin-2-yl]oxy}methyl)piperidine-1-carboxylate;
1-methylcyclopropyl 4-({[5-(2-oxo-4-{[2-(1H-pyrazole-1-yl)ethane]sulfonyl}piperazine-1-yl)pyrazin-2-yl]oxy}methyl)piperidine-1-carboxylate;
1-methylcyclopropyl 4-[({5-[4-(1-methylpyrrolidine-3-sulfonyl)-2-oxopiperidin-1-yl]pyrazin-2-yl}oxy)methyl]piperidine-1-carboxylate;
1-methylcyclopropyl 4-({[5-(4-{[2-(3,3-diversecity-1-yl)ethane] sulfonyl}-2-oxopiperidin-1-yl)pyrazin-2-yl]oxy)methyl)piperidine-1-carboxylate;
1-m is telekabel 4-[({5-[4-(azetidin-3-sulfonyl)-2-oxopiperidin-1-yl]pyrazin-2-yl}oxy)methyl]piperidine-1-carboxylate;
1-methylcyclopropyl 4-({[5-(4-{[3-(3,3-diversecity-1-yl)propane]sulfonyl}-2-oxopiperidin-1-yl)pyrazin-2-yl]oxy}methyl)piperidine-1-carboxylate;
1-methylcyclopropyl 4-({[5-(4-{[3-(azetidin-1-yl)propane]sulfonyl}-2-oxopiperidin-1-yl)pyrazin-2-yl]oxy}methyl)piperidine-1-carboxylate;
1-methylcyclopropyl 4-{[(5-{2-oxo-4-[(3S)-pyrrolidin-3-sulfonyl]piperazine-1-yl}pyrazin-2-yl)oxy]methyl}piperidine-1-carboxylate;
1-methylcyclopropyl 4-{[(5-{2-oxo-4-[(3R)pyrrolidin-3-sulfonyl]piperazine-1-yl}pyrazin-2-yl)oxy]methyl}piperidine-1-carboxylate;
1-methylcyclopropyl 4-{[(5-{4-[(3S)-1-methylpyrrolidine-3-sulfonyl]piperazine-1-yl}pyrazin-2-yl)oxy]methyl}piperidine-1-carboxylate;
1-methylcyclopropyl 4-{[(5-{4-[(3R)-1-methylpyrrolidine-3-sulfonyl]piperazine-1-yl}pyrazin-2-yl)oxy]methyl}piperidine-1-carboxylate;
1-methylcyclopropyl 4-{[(5-{4-[(3S)-pyrrolidin-3-sulfonyl]piperazine-1-yl}pyrazin-2-yl)oxy]methyl}piperidine-1-carboxylate;
1-methylcyclopropyl 4-{[(5-{4-[(3R)-pyrrolidin-3-sulfonyl]piperazine-1-yl}pyrazin-2-yl)oxy]methyl}piperidine-1-carboxylate;
1-methylcyclopropyl 4-[({5-[4-(azetidin-3-sulfonyl)piperazine-1-yl]pyrazin-2-yl}oxy)methyl]piperidine-1-carboxylate;
1-methylcyclopropyl 4-{[(5-{2-oxo-4-[(pyrrolidin-3-Ilmatar)sulfonyl]piperazine-1-yl}pyrazin-2-yl)oxy]methyl}piperidine-1-carboxylate;
1-methylcyclopropyl 4-[({5-[4-(1-hydroxy-2-methylpropan-2-sulfonyl)piperazine-1-yl] pyrazin-2-yl}on the si)methyl]piperidine-1-carboxylate;
1-methylcyclopropyl 4-{[(5-{4-[(2-hydroxyethane)sulfonyl]piperazine-1-yl}pyrazin-2-yl)oxy]methyl}piperidine-1-carboxylate;
1-methylcyclopropyl 4-{[(5-{4-[(azetidin-3-Ilmatar)sulfonyl]piperazine-1-yl}pyrazin-2-yl)oxy]methyl}piperidine-1-carboxylate;
1-methylcyclopropyl 4-({[5-(4-{[(1-methylpyrrolidine-2-yl)methane]sulfonyl}-2-oxopiperidin-1-yl)pyrazin-2-yl]oxy}methyl)piperidine-1-carboxylate;
1-methylcyclopropyl 4-{[(5-{2-oxo-4-{[3-(1H-pyrrolidin-3-sulfonyl]piperazine-1-yl}pyrazin-2-yl)oxy]methyl}piperidine-1-carboxylate;
1-methylcyclopropyl 4-[({5-[4-(1-methylisatin-3-sulfonyl)piperazine-1-yl]pyrazin-2-yl}oxy)methyl]piperidine-1-carboxylate;
1-methylcyclopropyl 4-[({5-[4-(1-methylisatin-3-sulfonyl)-2-oxopiperidin-1-yl]pyrazin-2-yl}oxy)methyl]piperidine-1-carboxylate;
1-methylcyclopropyl 4-({[5-(4-{[(1-methylisatin-3-yl)methane]sulfonyl}-2-oxopiperidin-1-yl)pyrazin-2-yl]oxy}methyl)piperidine-1-carboxylate;
1-methylcyclopropyl 4-({[5-(4-{[(1-methylisatin-3-yl)methane]sulfonyl}piperazine-1-yl)pyrazin-2-yl]oxy}methyl)piperidine-1-carboxylate;
1-methylcyclopropyl 4-[({5-[4-({3-[(3S,4S)-3,4-dihydroxypyrrolidine-1-yl]propane}sulfonyl)-2-oxopiperidin-1-yl]pyrazin-2-yl}oxy)methyl]piperidine-1-carboxylate;
1-methylcyclopropyl 4-[({5-[4-({2-[(3S,4S)-3,4-dihydroxypyrrolidine-1-yl]ethane}sulfonyl)-2-oxopiperidin-1-yl]pyrazin-2-yl}oxy)methyl]piperidine-1-carboxylate;
1-methylcyclopropyl 4-{[(5-4-[(azetidin-3-Ilmatar)sulfonyl]-2-oxopiperidin-1-yl}pyrazin-2-yl)oxy]methyl}piperidine-1-carboxylate;
1-methylcyclopropyl 4-{[(5-{2-oxo-4-[(pyrrolidin-2-Ilmatar)sulfonyl]piperazine-1-yl}pyrazin-2-yl)oxy]methyl}piperidine-1-carboxylate;
1-methylcyclopropyl 4-({[5-(3-methanesulfonamido-1-yl)pyrazin-2-yl]oxy}methyl)piperidine-1-carboxylate;
1-methylcyclopropyl 4-({[5-(2-oxo-4-{[3-(pyrrolidin-1-yl)propane]sulfonyl}piperazine-1-yl)pyrazin-2-yl]oxy}methyl)piperidine-1-carboxylate;
1-methylcyclopropyl 4-({[5-(4-{[3-(morpholine-4-yl)propane]sulfonyl}-2-oxopiperidin-1-yl)pyrazin-2-yl]oxy}methyl)piperidine-1-carboxylate;
1-methylcyclopropyl 4-({[5-(4-{[(3-methyloxiran-3-yl)methane]sulfonyl}piperazine-1-yl)pyrazin-2-yl]oxy}methyl)piperidine-1-carboxylate;
1-methylcyclopropyl 4-({[5-(4-{[3-(atomic charges)propane]sulfonyl}-2-oxopiperidin-1-yl)pyrazin-2-yl]oxy}methyl)piperidine-1-carboxylate;
1-methylcyclopropyl 4-[({5-[(2E)-2-(hydroxyimino)-4-methanesulfonylaminoethyl-1-yl] pyrazin-2-yl}oxy)methyl]piperidine-1-carboxylate;
1-methylcyclopropyl 4-{[(5-{4-[(3-chlorpropyl)sulfonyl]-2-oxopiperidin-1-yl}pyrazin-2-yl)oxy]methyl}piperidine-1-carboxylate;
1-methylcyclopropyl 4-{[(5-{4-[(3-hydroxypropan)sulfonyl]-2-oxopiperidin-1-yl}pyrazin-2-yl)oxy]methyl}piperidine-1-carboxylate;
1-methylcyclopropyl 4-{[(5-{2-oxo-4-[(3R)-oxolan-3-sulfonyl]piperazine-1-yl}pyrazin-2-yl)oxy]methyl}piperidine-1-carboxylate;
1-methylcyclopropyl 4-{[(5-{2-oxo-4-[(3S)-oxolan-3-sulfonyl]piperazine-1-yl} pyrazin-yl)oxy]methyl}piperidine-1-carboxylate;
1-methylcyclopropyl 4-({[5-(4-{[(1-hydroxyisopropyl)methane]sulfonyl}piperazine-1-yl)pyrazin-2-yl]oxy}methyl)piperidine-1-carboxylate;
1-methylcyclopropyl 4-({[5-(4-{[2-(1-hydroxyisopropyl)ethane]sulfonyl}piperazine-1-yl)pyrazin-2-yl]oxy}methyl)piperidine-1-carboxylate;
1-methylcyclopropyl 4-[({5-[4-({[1-(benzyloxy)cyclopropyl]methane} sulfonyl)piperazine-1-yl]pyrazin-2-yl}oxy)methyl]piperidine-1-carboxylate;
1-methylcyclopropyl 4-({[5-(4-{[2-(1-hydroxyisopropyl)ethane]sulfonyl}-2-oxopiperidin-1-yl)pyrazin-2-yl]oxy}methyl)piperidine-1-carboxylate;
1-methylcyclopropyl 4-{2,6-debtor-4-[3-(N-methylmethanesulfonamide)azetidin-1-yl]phenoxymethyl}piperidine-1-carboxylate;
1-methylcyclopropyl 4-[2,6-debtor-4-(3-methanesulfonamido-1-yl)phenoxymethyl]piperidine-1-carboxylate;
1-methylcyclopropyl 4-{2,6-debtor-4-[3-(2-methylpropan-1 sulphonamido)azetidin-1-yl] phenoxymethyl}piperidine-1-carboxylate;
1-methylcyclopropyl 4-{4-[3-(N,2 DIMETHYLPROPANE-1 sulphonamido)azetidin-1-yl]-2,6-diferenciate}piperidine-1-carboxylate;
5-ethyl-2-{4-[({2-methanesulfonyl-1H,2H,3H,4H-pyrazino[1,2-a]indol-8-yl}oxy)methyl]piperidine-1-yl}pyrimidine;
1-{[1-(5-ethylpyrimidine-2-yl)piperidine-4-yl]oxy}-5-methanesulfonyl-8-oxa-5-azatricyclo[7.4.0.0{2.7}]Tribeca-1(13),2(7),9,11-tetraen;
1-{[1-(5-ethylpyrimidine-2-yl)piperidine-4-yl]methoxy}-5-methanesulfonyl-8-oxa-5-azatricyclo[7.4.0.0{2.7}]Tribeca-1(13),2(7),9,11-Tetra is n;
tert-butyl 4-[({2-methanesulfonyl-1H,2H,3H,4H-pyrazino[1,2-a]indol-8-yl}oxy)methyl]piperidine-1-carboxylate;
1-methylcyclopropyl 4-[({2-methanesulfonyl-1H,2H,3H,4H-pyrazino[1,2-a]indol-8-yl}oxy)methyl]piperidine-1-carboxylate;
propan-2-yl 4-{3-[3-(1-methanesulfonamido-4-yl)phenoxy]propyl}piperidine-1-carboxylate;
propan-2-yl 4-{2-[3-(1-methanesulfonamido-4-yl)phenoxy]ethyl}piperidine-1-carboxylate;
propan-2-yl 4-[3-(1-methanesulfonamido-4-yl)phenoxymethyl]piperidine-1-carboxylate;
1-methylcyclopropyl 4-({[5-(4-methanesulfonyl-2-sulfanilamides-1-yl)pyrazin-2-yl]oxy}methyl)piperidine-1-carboxylate;
1-methylcyclopropyl (3S,4S)-3-hydroxy-4-{[(6-{4-[(2-methylpropan)sulfonyl]piperazine-1-yl}pyridine-3-yl)oxy]methyl}piperidine-1-carboxylate;
1-methylcyclopropyl (3R,4S)-3-hydroxy-4-{[(6-{4-[(2-methylpropan)sulfonyl]piperazine-1-yl}pyridine-3-yl)oxy]methyl}piperidine-1-carboxylate;
1-methylcyclopropyl 4-{[(6-{4-[(2-hydroxy-2-methylpropan)sulfonyl]piperazine-1-yl}pyridine-3-yl)oxy]methyl}piperidine-1-carboxylate;
1-methylcyclopropyl (3S,4R)-3-methoxy-4-{[(6-{4-[(2-methylpropan)sulfonyl]piperazine-1-yl}pyridine-3-yl)oxy]methyl}piperidine-1-carboxylate;
1-methylcyclopropyl 4-({[5-(4-{[3-(3,3-diversecity-1-yl)propane]sulfonyl}piperazine-1-yl)pyrazin-2-yl]oxy}methyl)piperidine-1-carboxylate;
1-methylcyclopropyl 4-({[5-(4-{[3-(azetidin-1-yl)propane]sulfonyl}piperazine-1-yl)PIR is Zin-2-yl]oxy}methyl)piperidine-1-carboxylate;
1-methylcyclopropyl-{[(5-{4-[(3-methoxypropan)sulfonyl]piperazine-1-yl}pyrazin-2-yl)oxy]methyl}piperidine-1-carboxylate;
1-methylcyclopropyl 4-{[(6-{4-[(3-chlorpropyl)sulfonyl]-2-oxopiperidin-1-yl}pyridine-3-yl)oxy]methyl}piperidine-1-carboxylate;
1-methylcyclopropyl 4-({[5-(4-{[2-(azetidin-1-yl)ethane]sulfonyl}piperazine-1-yl)pyrazin-2-yl]oxy}methyl)piperidine-1-carboxylate;
1-methylcyclopropyl 4-({[6-(4-{[3-(azetidin-1-yl)propane]sulfonyl}piperazine-1-yl)pyridine-3-yl]oxy}methyl)piperidine-1-carboxylate;
1-methylcyclopropyl 4-[({5-[4-(pyrrolidin-3-sulfonyl)piperazine-1-yl]pyrazin-2-yl}oxy)methyl]piperidine-1-carboxylate;
1-methylcyclopropyl 4-({[5-(4-{[2-(3,3-diversecity-1-yl)ethane]sulfonyl}piperazine-1-yl)pyrazin-2-yl]oxy}methyl)piperidine-1-carboxylate;
1-methylcyclopropyl 4-{[(6-{4-[(3-hydroxypropan)sulfonyl]-2-oxopiperidin-1-yl}pyridine-3-yl)oxy]methyl}piperidine-1-carboxylate;
1-methylcyclopropyl 4-({[6-(4-{[3-(azetidin-1-yl)propane]sulfonyl}-2-oxopiperidin-1-yl)pyridine-3-yl]oxy}methyl)piperidine-1-carboxylate;
1-methylcyclopropyl 4-[2,6-debtor-4-(4-methanesulfonyl-2-oxopiperidin-1-yl)phenoxymethyl]piperidine-1-carboxylate; and 1-methylcyclopropyl 4-[({5-[4-(oxetan-3-sulfonyl)-2-oxopiperidin-1-yl]pyrazin-2-yl}oxy)methyl]piperidine-1-carboxylate.

9. The compound according to claim 1, where the compound is 2-(4-(methylsulphonyl)piperazine-1-yl)-5-((1-(5-(trifluoromethyl)Piri is in-2-yl)piperidine-4-yl)methoxy)pyrazin formula
.

10. The compound according to claim 1, where the compound is a 1-methylcyclopropyl 4-((5-(4-(methylsulphonyl)piperazine-1-yl)pyrazin-2-yloxy)methyl)piperidine-1-carboxylate of the formula
.

11. The compound according to claim 1, where the compound is a 5-isopropyl-3-(4-((4-(1-(methylsulphonyl)-1,2,3,6-tetrahydropyridine-4-yl)phenoxy)methyl)piperidine-1-yl)-1,2,4-oxadiazol formula
.

12. The compound according to claim 1, where the compound is a 1-methylcyclopropyl (3S,4R)-3-methoxy-4-{[(6-{4-[(2-methylpropan)sulfonyl]piperazine-1-yl}pyridine-3-yl)oxy]methyl}piperidine-1-carboxylate of the formula
.

13. The compound according to claim 1, where the compound is a 1-methylcyclopropyl 4-(((5-(4-((3-hydroxypropyl)sulfonyl)piperazine-1-yl)pyrazin-2-yl)oxy)methyl)piperidine-1-carboxylate of the formula
.

14. The compound according to claim 1, where the compound is a 1-methylcyclopropyl 4-({[5-(4-{[2-(3,3-diversecity-1-yl)ethane]sulfonyl}piperazine-1-yl)pyrazin-2-yl]oxy}methyl)piperidine-1-carboxylate of the formula
.

15. The compound according to claim 1, where the compound is a 1-methylcyclopropyl 4-((5-(4-(methylsulphonyl)-2-oxopiperidin-1-yl)pyrazin-2-yloxy)methyl)piperidine-1-carboxylate of the formula
.

16. Soy is inania according to claim 1, where the connection is a 1-methylcyclopropyl 4-({[5-(4-{[3-(azetidin-1-yl)propane]sulfonyl}-2-oxopiperidin-1-yl)pyrazin-2-yl]oxy}methyl)piperidine-1-carboxylate of the formula
.

17. The compound according to claim 1, where the compound is a 1-methylcyclopropyl 4-{[(5-{2-oxo-4-[(3S)-pyrrolidin-3-sulfonyl]piperazine-1-yl}pyrazin-2-yl)oxy]methyl}piperidine-1-carboxylate of the formula
.

18. The compound according to claim 1, where the compound is a 1-methylcyclopropyl 4-((2,6-debtor-4-(1-(methylsulphonyl)piperidine-4-yl)phenoxy)methyl)piperidine-1-carboxylate of the formula
.

19. The compound according to claim 1, where the compound is a 1-methylcyclopropyl 4-((2,6-debtor-4-(1-(3-hydroxypropanesulfonic)piperidine-4-yl)phenoxy)methyl)piperidine-1-carboxylate of the formula
.

20. The compound according to claim 1, where the compound is a 1-methylcyclopropyl 4-[2,6-debtor-4-(4-methanesulfonyl-2-oxopiperidin-1-yl)phenoxymethyl]piperidine-1-carboxylate of the formula
.

21. Pharmaceutical composition having modulating activity against receptor GPR119, containing a compound according to any one of claims 1 to 20 in a therapeutically effective amount, in combination with pharmaceutically acceptable excipients.

22. The pharmaceutical composition is, intended for treatment of a disease or condition containing the compound according to any one of claims 1 to 20 in a therapeutically effective amount together with a pharmaceutically acceptable excipient, where the disease or condition selected from obesity, diabetes type 1, diabetes type 2, hyperlipidemia, idiopathic type 1 diabetes, latent autoimmune diabetes in adults, early type 2 diabetes, the children's atypical diabetes, adult diabetes in children associated with malnutrition diabetes and diabetes in pregnancy.

23. The method of modulating the activity of GPR119, including the introduction of a system or subject in need this, the compounds according to claims 1 to 20, or its pharmaceutically acceptable salts or pharmaceutical compositions containing it, in therapeutically effective amounts, thereby modulating the specified activity of GPR119.

24. The method according to item 23, where the connection according to claim 1 in direct contact with GPR119.

25. The method according to paragraph 24, where the contacting occurs in vitro or in vivo.

26. The method of treatment of a disease or condition in which modulation of GPR119 activity can prevent, inhibit or facilitate the pathology and/or symptomatology of the disease or condition including introduction to the subject of the compounds according to claims 1 to 20, or its pharmaceutically acceptable salts or pharmaceutical compositions containing it, in therapeuti the Eski effective amount.

27. The method according to p, in which the disease or condition selected from obesity, diabetes type 1, diabetes type 2, hyperlipidemia, idiopathic type 1 diabetes, latent autoimmune diabetes in adults, early type 2 diabetes, the children's atypical diabetes, adult diabetes in children associated with malnutrition diabetes and diabetes in pregnancy.



 

Same patents:

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of formulae and including their stereoisomers, as well as pharmaceutically acceptable salt, where X denotes O or S; R1 is selected from H, F, CI, Br, I, CN, -CR14R15-NR16R17, -CR14R15-NHR10, -(CR14R15)NR10R11, -(CR14R15)nNR12C(=Y)R10, -(CR14R15)nNR12S(O)2R10, -(CR14R15)mOR10, -(CR14R15)nS(O)2R10, -C(OR10)R11R14, -C(R14)=CR18R19, -C(=Y)OR10, -C(=Y)NR10R11, -C(=Y)NR12OR10, -C(=O)NR12S(O)2R10, -C(=O)NR12(CR14R15)mNR10R11, -NHR12, -NR12C(=Y)R10, -S(O)2R10, -S(O)2NR10R11, C2-C12 alkyl, C2-C8 alkenyl, C2-C8 alkynyl, C3-C4 carbocyclyl, piperidinyl, thiopyranyl, phenyl or C5-C6 heteroaryl; R2 is selected from H, C2-C12 alkyl and thiazolyl; R3 denotes a condensed bicyclic heteroaryl selected from indazole, indole, benzoimidazole, pyrrolopyridine, imidazopyridine and quinoline; R10, R11 and R12 independently denote H, C2-C12 alkyl, C3 carbocyclyl, heterocyclyl selected from pyrrolidine, morpholine and piperazine, phenyl or heteroaryl selected from pyrazole, pyridine, benzothiophene; or R10 and R11 together with a nitrogen atom with which they are bonded possibly form a saturated C3-C6 heterocyclic ring, possibly containing one additional ring atom selected from N or O, where said heterocyclic ring is possibly substituted with one or more groups independently selected from oxo, (CH2)mOR10, NR10R11, SO2R10, C(=O)R10, NR12S(O)R11, C(=Y)NR10R11, C1-C12 alkyl and heterocyclyl selected from pyrrolidine; R14 and R15 are independently selected from H or C1-C12 alkyl; R16 and R17 independently denote H or phenyl; R18 and R19 together with a carbon atom with which they are bonded form a C3-C20 heterocyclic ring, where said alkyl, alkenyl, alkynyl, carbocyclyl, heterocyclyl, phenyl, heteroaryl, piperidinyl and condensed bicyclic heteroaryl possibly substituted with one or more groups independently selected from F, CI, Br, I, CF3, -C(=Y)R10, -C(=Y)OR10, oxo, R10, -C(=Y)NR10R11, -(CR14R15)nNR10R11, -NR10R11, -NR12C(=Y)R10, -NR12C(=Y)NR10R11, -NR12SO2R10, OR10, SR10, -S(O)2R10, -S(O)2NR10R11, possibly substituted with carbocyclyl, selected from cyclopropyl, possibly substituted heterocyclyl selected from piperazine, possibly substituted with alkyl and alkylsulphonyl, pyrrolidine, morpholine, piperdine, possibly substituted CH3, phenyl and possibly substituted heteroaryl selected from imidazole and triazole; Y denotes O; m equals 0, 1 or 2; n equals 1 and t equals 2. The invention also relates to a pharmaceutical composition which modulates lipid kinase activity, based on said compounds.

EFFECT: obtaining novel compounds and a composition based on said compounds, which can be used to treat lipid kinase-mediated diseases, for example, cancer.

48 cl, 2 tbl, 372 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel pyrazole derivatives of general formula I

and pharmaceutically acceptable salts thereof, where n equals 1 or 2, m equals 0, 1 or 2, A contains in the ring a group selected from -CR1=, -CR2=, -CR3=, -CR4= and -CR5=, where 0 or 1 in these groups is replaced with N, R1, R2, R3, R4 and R5 are independently selected from a group comprising hydrogen, hydroxy, halogen, cyano, cyano(C1-C6)alkyl, C4-C6 heterocycloalkyl-C0-alkyl, where the said heterocycloalkyl contains 1-2 heteroatoms selected from nitrogen and oxygen atoms, C5heteroaryl-(C0-C4)alkyl, where the said heteroaryl contains 1-4 heteroatoms selected from nitrogen atoms, -XSO2R11, -XSO2NR11R12, -XSO2NR11C(O)R12, -XC(NR11)NR11OR12, -XCR11=NOR12, -XC(O)R11, -XC(O)OR11, -XNR11R12, -XC(O)NR11R12, -XOC(O)NR11R12, -XNR11C(O)NR11R12, -XNR11XOR12; -XN(XOR12)2, -XNR11XC(O)OR12 -XNR11XNR11C(O)R12 -XNR11XNR11R12, -XNR11C(O)R12, where each X is independently selected from a group comprising a chemical bond and C1-C4alkylene, each R11 is selected from a group comprising hydrogen and C1-C6alkyl, and R12 is selected from a group comprising hydrogen, C1-C6alkyl and phenyl, or R11 and R12 together with a nitrogen atom to which R11 and R12 are bonded form C6heterocycloalkyl. Said heteroaryl or heterocycloalkyl in R1, R2, R3, R4 or R5 optionally contains one substitute selected from a group comprising hydroxyl, cyano, C1-C6alkyl, hydroxyl(C1-C6)alkyl and carboxy, R6 and R7 independently denote hydrogen, R8 is selected from a group comprising C1-C6alkyl, halogen(C1-C3)alkyl, -CH2OR8a and -COOR8a or two R8 groups bonded to different carbon atoms, together form a (C1-C2)alkyl bridge, or two R8a groups bonded to one carbon atom form a (C3-C8)cycloalkyl group, where R8a is selected from a group comprising hydrogen and C1-C6alkyl, R9 is selected from a group comprising phenyl and C6heteroaryl, where the said heteroaryl contains 1-2 heteroatoms selected from nitrogen atoms, and C9heteroaryl, where the said heteroaryl contains 1-2 heteroatoms selected from nitrogen and oxygen atoms, where the said phenyl or heteroaryl in R9 is optionally substituted with 1-2 substitutes independently selected from a group comprising halogen, cyano, hydroxy, C1-C3alkyl, halogen(C1-C3)alkyl, hydroxy(C1-C3)alkyl, -C(O)R13, -C(O)NR13R14, where each of R13 and R14 is independently selected from a group comprising hydrogen and C1-C6alkyl, R10 denotes hydrogen, Y and Z are independently selected from a group comprising CR20 and N, where R20 denotes hydrogen, provided that compounds of formula I do not include compounds of formula II, which are described in claim 1, and provided that compounds of formula I do not include compounds which are: 1-(4-fluorophenyl)-4-((3-phenyl-1H-pyrazol-4-yl)methyl)piperazine, 1- ((3-(4-fluorophenyl)-1H-pyrazol-4-yl)methyl)-4-(4-(trifluoromethyl)-(pyridin-2- yl)piperazine, 1-((3-(4-fluorophenyl)-1H-pyrazol-4-yl)methyl)-4-(5-(trifluoromethyl)-(pyridin-2-yl)piperazine and 1-((3-(4-fluorophenyl)-1H-pyrazol-4-yl)methyl)-4-(5-fluoropyridin-2-yl)piperazine. The invention also relates to specific compounds obtained.

EFFECT: novel pyrazole derivatives which can be used in treating diseases or disorders which are mediated by disrupted activation of the said compound are obtained.

8 cl, 1 tbl, 4 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: claimed invention relates to novel compounds of formula 1: or its pharmaceutically acceptable salt; in which each R1 and R8 independently represents H or hydroxyl; each R2 and R9 independently represents H or hydroxyl; R5 represents H; each R3, R4, R6, R7, R13 and R14 independently represents H; or R1 and R2, taken together, form =O; or R4 and R5, taken together form double bond; or R5 and R6, taken together form double bond; R10 and R11, taken together form double bond; R12 represents H, alkyl, hydroxyl, aralkyl, halogenalkyl, alcoxyl,- -[(W)- N(R21)C(O)]qR21, -[(W)-N(R21)SO2]qR21, -[(W)-O]qR21 or -[(W)-N(R21)]qR21; where each W independently represent bivalent alkyl or aralkyl radical, and q is equal 1, 2, 3 or 4; each R15, R16 and R17 independently represent H; each R18 and R19 independently represents H; and each R21 independently represents H, alkyl, aryl or aralkyl. Invention also relates to pharmaceutical composition. Claimed invention provides cycloamine analogues which can be applied to counteract phenotypic effects of undesirable activation of Hedgehog pathway, such as acquiring function from Hedgehog, Ptc loss of function or mitigated acquired from function mutations.

EFFECT: compounds by claimed invention are especially applicable in cancer treatment.

19 cl, 1 tbl, 28 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel compounds, specifically to 4-substituted-3-(1-alkyl-2-chloro-1H-indol-3-yl)furan-2,5-diones of general formula I , where R1=H, C1-C6 alkyl; R2=H, C1-C6 alkyl, C1-C6 alkoxy; R3=phenyl, naphthyl, 2-phenyl-1-ethenyl, thienyl, furyl, pyrrolyl, benzothiophenyl, benzofuranyl, indolyl, synthesis method thereof and use as compounds capable of photochemical generation of stable fluorophores of formula II, which can be used, for instance in information storage systems, particularly as photosensitive components of material for three-dimensional recording and storage of information. The invention also relates to novel 4,5-substituted-6-alkyl-1H-furo[3,4-c]carbazole-1,3(6H)diones of general formula II , where R1=H, C1-C6 alkyl; R2=H, C1-C6 alkyl, C1-C6 alkoxy; R4=H, R5=phenyl, R4, R5=benzo, naphtho, thieno, furo, pyrrolo, benzothieno, benzofuro, indolo, method for synthesis of said compounds and use as fluorophores.

EFFECT: obtaining novel compounds and possibility of using said compounds as fluorophores.

14 cl, 2 tbl, 8 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel cyclic amine compounds of formula (1) or pharmaceutically acceptable salts thereof: . In formula (1), X is O, S, NR2 (where R2 is H, C1-C12 alkyl); when X is O, S, then R1 is H, CN, COOH, C2-C13 alkoxycarbonyl, carbamoyl group; and when X is NR2 (where R2 assumes values given above), R1 is CN; Ar1 and Ar2 are identical or different and each represents an aryl which can be substituted with 1-3 halogens; or Ar1 and Ar2 together with neighbouring carbon atoms to which they are bonded form a group with formula (b): (where ring S and ring T are identical and each is a benzene ring; Y is O); ring B is a benzene ring which can be substituted with 1-3 substitutes independently selected from a group comprising halogen, C1-C12 alkyl, C1-C8 halogenalkyl, C1-C12 alkoxy, C1-C8 halogenalkoxy group; n is an integer from 1 to 10; p, q are identical or different and each is an integer equal to 1 or 2. Formula (1) compounds are bonding inhibitors of the α2C-adrenoreceptor.

EFFECT: possibility of using compounds in pharmaceutical compositions.

7 cl, 1 tbl, 8 ex

FIELD: chemistry.

SUBSTANCE: in formula compounds, each of R1, R2, R3, R4 is a substitute for a cyclic system, chosen from hydrogen, halogen, C1-C6-alkyl; C1-C6-alkoxy group; X is a heteroatom, chosen from oxygen or sulphur; R5 and R6 independently represent amino group substitutes, chosen from hydrogen, possibly substituted C1-C6-alkyl; possibly substituted C3-C6-cycloalkyl, which can be annealed with a benzene ring; possibly substituted phenyl, which can be annealed with dioxole, dioxine, -(CH2)n group, where n=4 to 6, or with a 5 or 6-member possibly substituted and possibly condensed azaheterocyclyl; possibly substituted saturated or unsaturated 5-6-member heterocyclyl, containing 1-2 heteroatoms, chosen form nitrogen, oxygen, sulphur and possibly condensed with a benzene ring, or R5 and R6 together with the nitrogen atom to which they are bonded, form an optionally substituted 5 or 6-member azahetero ring, possibly containing an additional heteroatom, chosen from nitrogen, and possibly annealed with a benzene ring or spiro-condensed with dioxole, where substitutes in the said alkyl, cycloalkyl, phenyl and heterocyclyl are chosen from halogen atoms, possibly substituted C1-C6-alkyl, CF3, possibly substituted C3-C6-cycloalkyl, possibly substituted phenyl, 5 or 6-member heterocyclyl, nitro group, substituted amino group, alkyloxycarbonyl, substituted carbonyl, aminocarbonyl, alkylsulphanyl.

EFFECT: design of an efficient method of producing new substituted furo[2,3-b]quinoline-2-carboxamides and substituted thieno[2,3-b]quinoline-2-carboxamides or their racemates, or their optical isomers, as well as their pharmaceutically acceptable salts and/or hydrates of general formula (I), which have antituberculous activity.

9 cl, 1 dwg, 7 tbl, 5 ex

FIELD: pharmacology.

SUBSTANCE: invention relates to novel compounds - tetrahydronaphthyridine derivatives of formula (I) or their pharmaceutically acceptable salts, where R1 represents C1-6alkoxycarbonyl group optionally substituted with 1-5 substituents, etc; R2 represents C1-6alkyl group; R3 represents hydrogen or and all; R4 represents C1-4alkylene group; R5 represents optionally substituted unsaturated 5-8-member heterocyclic group containing 1-4 heteroatoms independently selected from oxygen and nitrogen atoms; R6, R7 and R8 represent independently hydrogen atom, hydroxygroup, cyanogroup, C1-6alkyl group, C1-6alkoxygroup, mono- or di- C1-6alkylcarbamoyl group or mono- or di- C1-6alkylaminogroup, optionally substituted with 1-6 substituents independently selected from halogen atom, C1-6alkoxygroup and aminogroup; R10 represents optionally substituted with 1-2 substituents phenyl group; which possess inhibiting activity with respect to cholesteryl ester transfer protein (CETP).

EFFECT: novel tetrahydronaphthyridine derivatives and method of obtaining them.

12 cl, 408 ex, 38 tbl

FIELD: chemistry.

SUBSTANCE: present invention relates to new annelated azaheterocyclic amides, including a pyrimidine fragment, with the general formula 1, method of obtaining them and their application in the form of free bases or their pharmaceutically accepted salts as inhibitors of P13K kinase, in compounds with the general formula 1: , where: X represents an oxygen atom, sulphur atom or not necessarily substituted at the nitrogen NH group, where the substitute is selected from lower alkyls and possibly a substituted aryl; Y represents an atom of nitrogen or substituted at the carbon atom CH group, where the substitute is selected from lower alkyls; Z represents an oxygen atom; R1 represents a hydrogen atom or not necessarily substituted C1-C6alkyl, or Z represents a nitrogen atom, which is together with a carbon atom, with which it is joined, form through Z and R1 annelated imidazole cycle; R2 and R3 independently from each other represent hydrogen, not necessarily substituted with C1-C6alkyl, C3-C6cycloalkyl, not necessarily substituted with phenyl, not necessarily substituted with 6-member aza-heteroaryl, under the condition, when Y represents a nitrogen atom, or R2 and R3 independently from each other represent not necessarily substituted C1-C6alkyl, not necessarily substituted with phenyl, not necessarily substituted with 5-7-member heterocycle with 1-2 heteroatoms, selected from nitrogen and oxygen, and possibly annelated with a phenyl ring, under the condition, when Y does not necessarily represent a substituted carbon atom at the CH group, and X represents an oxygen atom, sulphur atom, or R2 represents hydrogen, and R3 represents a substituted aminoC1-C6alkyl and not necessarily substituted 5-6-member aza-heterocycloalkyl, under the condition, when Y represents a group which is substituted at the CH atom, and X represents an oxygen atom, sulphur atom, or R2 represents hydrogen, and R3 represents phenyl which is not necessarily substituted, pyridyl which is not necessarily substituted, pyrimidinyl which is not necessarily substituted, under the conditions, when R1 represents a substituted aminoC1-C6alkyl, substituted C2-C3hydroxyalkyl and aza-heterocycloalkyl not necessarily substituted, Y represents a group with CH substituted, and X represents an oxygen atom, sulphur, and the substitute of the above indicated substituted alkyl, phenyl, heterocycle, pyridyl, pyrimidyl are selected from groups of hydroxyl-, cyano-groups, hydrogen, lower alkyls, possibly mono- or di-substituted lower alkyl sulfamoyl, carbamoyl, C1-C6alkoxycarbonyl, amino, mono- or di-lower alkyl-amine, N-(lower alkyl), N-(phenylC1-C6alkyl)amine, phenyl, possibly substituted with a halogen atom, C1-C6alkyl, haloid-C1-C6alkyl; phenylC1-C6alkyl, saturated or non-saturated 5-6-member heterocycle containing 1-2-heteroatoms, selected from nitrogen, oxygen and sulphur, and possible condensation with a benzene ring R4 represents hydrogen or a lower alkyl.

EFFECT: obtaining new annelated aza-heterocyclic amides, including a pyrimidine fragment, with the general formula with the possibility of their application in the form of free bases or their pharmaceutically accepted salts as inhibitors of PI3K kinase.

16 cl, 5 tbl, 5 ex

FIELD: chemistry.

SUBSTANCE: in general formula (I) , R1 represents similar or different 2 groups, each of which is selected from group consisting of C1-3alkyl, or when R1 are two adjacent groups, two groups R1, taken together, can form saturated or unsaturated 5- or 6-member cyclic group, which can have 1 or 2 oxygens as heteroatom; X represents oxygen or sulphur; values of other radicals are given in invention formula.

EFFECT: increase of composition efficiency.

16 cl, 11 tbl, 31 ex

FIELD: medicine; pharmacology.

SUBSTANCE: new annelated asaheterocycles include pyrimidine fragment of general formula I in the form of free bases or pharmaceutically acceptable salts. Compounds of this invention possess properties of PI3 kinase inhibitors. In general formula I X represents oxygen atom or sulphur atom; Z represents oxygen atom, R1 represents hydrogen atom or optionally substituted C1-C6alkyl, or Z represents nitrogen atom together with bound carbon atom forming through Z and R1 optionally substituted annelated imidazoline cycle; R2 represents optionally substituted C1-C6alkyl, optionally substituted C3-C8cycloalkyl, optionally substituted phenyl, possibly annelated with 5-6-term heterocyclyl containing heteroatoms chosen from oxygen and nitrogen, optionally substituted 5-6-term heterocyclyl containing heteroatoms chosen from nitrogen, oxygen and/or sulphur, possibly annelated with phenyl ring. Invention also concerns method of production of compounds, pharmaceutical compositions and medical products.

EFFECT: effective application for preparation of medical products for oncologic therapy.

14 cl, 3 dwg, 1 tbl, 4 ex

FIELD: chemistry.

SUBSTANCE: present invention refers to the field of organic chemistry, notably to derivatives of dihydroimidazole with the general formula (I) and to its pharmaceutically acceptable salts where X1 and X2 denote halogen; R1 and R2 are chosen from the group including -H, -CH3, -CH2CH3 on the condition that both R1 and R2 do not denote hydrogen; R3 denotes -H or -C(=O)-R7; and if R6 denotes hydrogen, then R4 denotes -OCH3, -OCH2CH3 or -OCH(CH3)2; R5 denotes -H, - halogen, -CF3, -OCH3, -C(CH3)2, - cyclopropyl, - cyano group, -C(CH3)3, -C(CH3)2OR (where R denotes -H), -C(CH3)2CH-OR (where R denotes -CH3), -C(CH3)2CN, -C(CH3)2COR (where R denotes -CH3), -SR (where R denotes -CH2CH3) or -SO2R (where R denotes -CH3, -CH2CH3, 1-pyrrolidine, -NH-tert-butyl); and if R6 does not denote hydrogen, then R4 denotes -OCH2CH3; R5 denotes hydrogen, -Cl, -OCH3, tert butyl; R6 denotes -Cl, cyclopropyl, -SO2R (where R denotes -CH3, 1-pyrrolidine, -NH-tert-butyl or -N(CH3)2); and R7 is chosen from the group including i) -CH3, -CH(CH3)2, -CH2CH(CH3)2, cyclopropyl, cyclobutyl, -CH2CH2Ph, 2-furanyl, phenyl or phenyl substituted with chlorine, -OCH3 or cyano group, ii) 1-piperidinyl, iii) -NRc2 (where Rc denotes -CH2CH2OH, -CH2CH2OCH3 or -CH2CH(OH)CH2OH, iv) substituted piperazidine with the formula where R is chosen from the group including a) hydrogen, c) -CH(CH3)2, k) -CH2CH2Rd (where Rd denotes -OH, -OCH3, -CF3, -SO2CH3, -NH2, -NHCOCH3, -NHSO2CH3, 4-morfolinil, 2-izotiazolidinil-1, 1-dioxide), l) -CH2CH2CH2Re (where Re denotes -OCH3, -SO2CH3, -SO2CH2CH3, -CN), m) -CH2-CO-Rh (where Rh denotes -NH2, 1-pyrrolidinyl, 4-morfolinil), n) -SO2Ri (where Ri denotes -CH3, -CH2CH3), o) -CORj (where Rj denotes -CH3, 2-tetrahydrofuranyl, -NH2, -N(CH3)2), p) 4-tetrahydro-2H-thiopiranyl-1,1-dioxide, q) 4-piperidinyl-1-acetyl, r) 4-piperidinyl-1-dimethylcarboxamide, and s) 3-tetrahydrothiophenyl-1,1-dioxide; v) substituted oxopiperazine with the formula where R denotes -H; and vi) substituted piperidine with the formula where R denotes -CONH2, -OH, -CH2OH, -CH2CH2OH, 1-pyrrolidinyl, 1-piperidinyl, 1-(4-methylpiperazinyl) or 4-morfolinil. Moreover, the invention refers to the pharmaceutical composition based on the compound with the formula (I), to application of the formula (I) compound for production of a drug, to the production process of the formula (I) compound.

EFFECT: new derivatives of dihydroimidazole that may be used as anticancer drugs.

40 cl, 204 ex

FIELD: pharmachology.

SUBSTANCE: invention describes new compounds with general formula (I-c) Where R1 is a radical (d-1) or (d-2) (radical values are given in the invention formula) and pharmaceutical composition containing them. The described compounds are the hepatitis C inhibitors and can be used in medicine.

EFFECT: enhanced hepatitis C inhibition.

5 cl, 1 tbl, 19 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to compounds selected from a group consisting of compounds of formula: and or to their pharmaceutically acceptable salts. Also, the invention refers to a pharmaceutical composition, as well as to using at least one compound under cl.1 and/or its pharmaceutically acceptable salts.

EFFECT: preparing new biologically active compounds which exhibit the properties of cycline-dependent kinase inhibitors.

11 cl, 86 tbl

Kinase inhibitors // 2440352

FIELD: chemistry.

SUBSTANCE: invention relates to a compound of formula : a pharmaceutically acceptable salt or solvate thereof, having Syk kinase inhibiting properties. The invention also relates to a pharmaceutical composition containing said compound, methods of treating diseases whose development is aided by c-kit receptor activity, such as arthritis, rheumatoid arthritis, tumours, mantle cell lymphoma, as well as a method of inhibiting angiogenesis.

EFFECT: improved method.

13 cl, 4 tbl, 10 dwg

FIELD: chemistry.

SUBSTANCE: invention describes novel compounds of general formula in which is or (values of radicals are given in the claim), a method of producing said compounds, a pharmaceutical composition containing said compounds and therapeutic application thereof.

EFFECT: compounds are cysteine protease inhibitors and can be used in medicine.

25 cl, 1 tbl, 41 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a method of producing 2,4,6,8-tetraazabicyclo[3.3.0]octane-3,7-dione (glycoluril). The reaction takes place at 80°C for 60 minutes, where concentrated sulphuric acid is used in an aqueous medium and reagents are taken in the following molar ratios: glyoxal 2.0; urea 4.0; sulphuric acid 0.4; water 12, and the freshly prepared glyoxal solution is added while stirring for 20 minutes, after which the mixture is stirred for 40 more minutes.

EFFECT: novel method of producing glycoluril, which increases output of the end product and is simpler.

1 cl, 1 tbl, 1 dwg

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of formula where R1 is selected from H, F, CI, Br, CF3, C1-C6 alkoxy and OH; R2 is selected from H and C1-C6 alkyl; n equals 1-5; m equals 0 or 1; and Y is selected from CH2, NR3, (NR3R4)+X-, O and S; R3 and R4 are independently selected from H and C1-C4 alkyl; and X- is selected from pharmaceutically acceptable anions. The invention also relates to a method of producing said compound and to an antiviral pharmaceutical composition based on said compound of formula (I).

EFFECT: obtaining novel compounds and a composition based on said compounds, which can be used in medicine to treat a viral diseases such as herpes.

19 cl, 2 tbl, 2 ex

FIELD: chemistry.

SUBSTANCE: invention describes novel macrocyclic compounds of formulae pharmaceutically acceptable salts or stereoisomers thereof, where R1 = -OR5, -NH-SO2R6; R2 = hydrogen; R3 = C1-6-alkyl; R4 = isoquinolinyl, possibly substituted; n equals 4 or 5; R5 = hydrogen; R6 = C3-7-cycloalkyl, and a pharmaceutical composition containing said compounds.

EFFECT: novel compounds have hepatitis C virus replication inhibitory action and can be used in medicine.

6 cl, 32 ex, 1 tbl

FIELD: chemistry.

SUBSTANCE: invention describes a compound of general formula where A1 is selected from the following formula R1c denotes a hydrogen atom, a lower alkenyl group or a -Q3-A3(R1d)R1e group; A3 denotes a methane or lower alkyl group; Q3 denotes a single bond; R1d and R1e independently denote a hydrogen atom, hydroxyl group, lower alkyl group or hydroxyl-containing lower alkyl group, or together form a lower alkylene group in which one or two or more methylene groups constituting the lower alkylene group can be independently substituted with an oxygen atom; R1 denotes a lower alkenyl group or a lower alkynyl group; R2 denotes a phenyl, pyridyl or thienyl group, which can contain a -Q4-A4(R1g)R1h group; A4 denotes a nitrogen atom, a lower alkyl group optionally substituted with a hydroxy-lower alkyl group, or a methane group optionally substituted with a halogen atom, a hydroxyl group, a lower alkyl group or a hydroxy-lower alkyl group; Q denotes a single bond or a lower alkylene group in which one or two or more methylene groups constituting the lower alkylene group can be independently substituted with an oxygen atom; R1g and R1h independently denote a hydrogen atom, a lower alkyl group or a lower alkylsulphonyl group; R5 and R6 independently denote a hydrogen atom, a lower alkyl group or a hydroxyl-containing lower alkyl group, or a pharmaceutically acceptable salt thereof. The invention also describes a pharmaceutical composition based on compounds of formula I, having anti-cancer activity, an anticancer agent, a codrug, as well as an exposure sensitising agent containing the pharmaceutical composition.

EFFECT: novel compounds are obtained and described, having excellent Well-kinase inhibitory action and can therefore be used in medicine, especially when treating different malignant tumours.

13 cl, 21 ex

FIELD: chemistry.

SUBSTANCE: invention describes novel macrocyclic compounds of general formulae (I-c) (I-d), pharmaceutically acceptable salt or stereoisomer thereof, where R1 = -OR11 or -NH-SO2R12; R2 = hydrogen and R3 =C1-6-alkyl; n = 3-6; W is a radical of formula , where R5 = phenyl, possibly substituted with C1-6alkyl or alkoxy; thiazolyl, possibly substituted with C1-6alkyl; or pyridyl; R11 denotes hydrogen; R12 = C3-7-cycloalkyl, and a pharmaceutical composition containing said compounds.

EFFECT: said compounds are hepatitis C virus inhibitors and can be used in medicine.

3 cl, 6 ex

FIELD: chemistry.

SUBSTANCE: invention refers to the compounds of formula (I): where R denotes cycloalkyl, heterocyclil, aryl, alkyl-O-C(O)-, alkanoyl or alkyl where each cycloalkyl, heterocyclil and aryl does not necessarily contain from 1 to 3 substitutes chosen from the group including alkyl, hydroxy group, halogen, cyano group, alkoxy group, alkyl-O-C(O)-, amino group, mono- or disubstituted by alkyl amino group and heterocyclil, and where each alkyl-O-C(O)-, alkyl, alkoxy group and heterocyclil does not necessarily have additional 1 to 3 substitutes chosen from the group including a hydroxy group, alkyl, halogen, carboxy group, alkoxy group, alkyl-O-C(O)-, alkanoyl, alkyl-SO2-, amino group, mono- or disubstituted by alkyl amino group and heterocyclil; R2 denotes alkyl, cycloalkyl, cycloalkylalkyl- or alkoxy group where alkyl does not necessarily contain from 1 to 3 substitutes chosen from the alkoxy group or halogen; R3 denotes R8-O-C(O)-, (R8)(R9)N-C(O)-, R8-C(O)-, where R8 and R9 independently denote alkyl, cycloalkyl, aryl, arylalkyl-, cycloalkylalkyl- or nonaromatic heterocyclil where each alkyl, cycloalkyl, aryl, arylalkyl-, cycloalkylalkyl- and nonaromatic heterocyclil do not necessarily contain from 1 to 3 substitutes chosen from the group including a hydroxy group, carboxy group, alkyl-O-C(O)-, alkyl-C(O)-O- and alkanoyl; R4 and R5 independently denote hydrogen, alkyl, alkynyl, alkoxy group, cycloalkyl, arylalkyl-, cycloalkylalkyl-, heteroarylalkyl-, monoalkylamino-C(O)-, dialkylcmino-C(O)- or dialkylamino-C(O)-alkyl-, where both these alkyl groups do not necessarily form a ring and where each alkyl, alkynyl, cycloalkyl, arylalkyl-, cycloalkylalkyl- heteroarylalkyl-, monoalkylamino-C(O)-, dialkylamino-C(O)- or dialkylamino-C(O)-alkyl- do not necessarily contain from 1 to 3 substitutes chosen from the group including alkyl, hydroxy group, halogen, carboxy group and alkoxy group; R6 and R7 independently denote hydrogen, halogenalkyl, halogen, dialkylamino group, alkoxy group, halogenalkoxy group, heteroaryl or alkyl-S(O)2- where each heteroaryl does not necessarily contain from 1 to 3 substitutes chosen from alkyl; where "heterocyclil" denotes fully saturated or nonsaturated aromatic or nonaromatic cyclic group that is represented by 5- or 6-membered monocyclic ring system containing at least one heteroatom chosen from nitrogen, oxygen and sulphur atoms; "heteroaryl" denotes 5- or 6-membered monocyclic ring system containing from 1 to 4 heteroatoms chosen from N, O and S; or to their pharmaceutically acceptable salts and their optical isomers, or to mixtures of the optical isomers. The invention also refers to the method of inhibition of the specimen's CETP activity, to the way of treatment of the specimen's abnormality or disease mediated by CETP or responsive to CETP inhibition, to the pharmaceutical composition, and to application of the formula (I) compounds.

EFFECT: production of new bioactive compounds that inhibit the CETP.

10 cl, 71 ex

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