Morpholinopyrimidine derivatives useful for treating proliferative disorders

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of formula or pharmaceutically acceptable salt thereof, synthesis methods thereof, pharmaceutical compositions containing said compounds, and use thereof to prepare a medicinal agent having mTOR kinase and/or PI3K kinase inhibiting action.

EFFECT: improved properties of the derivatives.

15 cl, 72 ex

 

The text descriptions are given in facsimile form.

1. The compound of formula (I)

or its pharmaceutically acceptable salt;
where m is equal to 0 is if 1;
Y1represents CH and Y2represents N;
X is a linker group selected from-NR4CR6R7-, -OCR6R7-, -SCR6R7-, -S(O)CR6R7-, -S(O)2CR6R7-, -C(O)NR4- , and-NR4C(O)-;
R1represents a group selected from adamantyl, methyl, ethyl, propyl, butyl, isobutyl, tert-butyl, cyclopentyl, cyclohexyl, phenyl, benzyl, oxetanyl, Venetia, pyrrolidinyl, pyrrolyl, imidazolyl, pyrazolyl, furanyl, teinila, pyridinyl, pyrimidinyl, pyrazinyl, pyrrolidinyl, pyrrolidinyl, pyrrolidinyl, pyrrolidinyl, imidazolidinyl, imidazolylalkyl, parasaissetia, pyrazolidine, furylmethyl, pornlatina, thienylmethyl, titilate, pyridinylmethyl, pyridinylmethyl, pyrimidinylidene, pyrimidinylidene, personalitie and personalitie, where this group optionally may be substituted by 1, 2 or 3 the substituting groups selected from halogen, cyano, nitro, R9, -OR9, -COR9, -CONR9R10, -NR9R10and-NR9COR10;
R2represents a

where a1and2selected from CH or N, provided that at least one of the A1or And2represents CH;
each R3if present, the present is the focus of a methyl;
R4represents hydrogen or C1-6alkyl;
R6and R7independently selected from hydrogen and C1-6of alkyl;
R9and R10independently represent hydrogen or a group selected from C1-6the alkyl, optionally substituted with halogen or hydroxy;
R17and R18represent hydrogen; and
R19represents hydrogen or a group selected from methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tert-butyl, penttila, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, teinila, imidazolyl, isoxazolyl, pyrazolyl, parasaissetia, pyridinyl and pyrimidinyl, where this group optionally may be substituted by one or more substituting groups selected from halogen, cyano, nitro, hydroxy, C1-6of alkyl, C1-6alkoxy, Halogens1-6of alkyl, Halogens1-6alkoxy, hydroxys1-6of alkyl, hydroxys1-6alkoxy, C1-6alkoxyl1-6of alkyl, C1-6alkoxyl1-6alkoxy, amino, C1-6alkylamino, bis(C1-6alkyl)amino, amino1-6of alkyl, (C1-6alkyl)amino1-6of alkyl, bis(C1-6alkyl)amino1-6of alkyl, tsianos1-6of alkyl, C1-6alkylsulfonyl,1-6alkylsulfonamides,1-6alkylsulfonyl(C1-6alkyl)amino, sulfamoyl,1-6alkyl is of sulfamoyl, bis(C1-6alkyl)sulfamoyl,1-6alkanolamine,1-6alkanoyl(C1-6alkyl)amino, carbamoyl,1-6allylcarbamate and bis(C1-6alkyl)carbamoyl.

2. The compound or its pharmaceutically acceptable salt according to claim 1, where the compound of formula (I) is a compound of formula (Ia) or (Ib)

or its pharmaceutically acceptable salt, where R1, R2, R3X, Y1and Y2have the meanings indicated in claim 1 for compounds of formula (I).

3. The compound or its pharmaceutically acceptable salt according to claim 2, where X is a linker group selected from-NR4CH2-, -Och2-, -Och(CH3)-, -OC(CH3)2-, -SCH2, -SCH(CH3)-, -SC(CH3)2-, -S(O)CH2-, -S(O)CH(CH3)-, -S(O)C(CH3)2-, -S(O)2CH2-, -S(O)2CH(CH3)-, -S(O)2C(CH3)2-, -C(O)NR4- , and-NR4C(O)-.

4. The compound or its pharmaceutically acceptable salt according to claim 2, where X represents-S(O)2CH2-, -S(O)2CH(CH3)- or-S(O)2C(CH3)2.

5. The compound or its pharmaceutically acceptable salt according to claim 2, where X represents-S(O)2C(CH3)2-.

6. The compound or its pharmaceutically acceptable salt according to claim 2, where R1represents a group selected the C methyl, ethyl, propyl, butyl, isobutyl, tert-butyl, cyclopropyl, cyclopentyl of cyclohexyl, phenyl, benzyl, Venetia, pyridinyl, pyrrolidinyl, pyrazolidine, furylmethyl, oxetanyl, imidazolidinyl, thienylmethyl, triazolylmethyl, thiadiazolyl and personalitie, where this group optionally may be substituted by 1 or 2 substituting groups selected from amino, halogen, cyano, methyl, methoxy, trifloromethyl, triptoreline, -NMe2, -NHCOCH3, -CONH2and-CONHCH3.

7. The compound or its pharmaceutically acceptable salt according to claim 2, where R1represents a group selected from methyl, ethyl, isopropyl, tert-butyl, cyclopropyl, cyclopentyl, cyclohexyl, -CH2CH2HE, -CH2CH2OMe, -CH2CH2NMe2, -CH2CH2NC(O)CH3, -CH2CONH2, phenyl, 3,5-dipthera, 4-ftoheia, 2-chlorphenyl, 4-chlorphenyl, 2-triptoreline, 2-methoxyphenyl, 2-methylphenyl, 4-acetamidophenyl, 4-AMINOPHENYL, pyridine-4-yl, pyridine-2-yl, oxetan-3-yl, 2-oxopyrrolidin-3-yl, 1-Mei-5-ylmethyl, 1 methylpyrrolidine-3-yl, thiazol-2-yl, 4-methylthiazole-2-yl and 3-methyl-1,3,4-thiadiazole-2-yl.

8. The compound or its pharmaceutically acceptable salt according to claim 2, where R1represents methyl, ethyl, isopropyl, tert-butyl, 4-forfinal, 3,5-differenl, pyridine-4-yl or Cyclops the sawdust.

9. The compound or its pharmaceutically acceptable salt according to claim 2, where R1represents methyl, ethyl, isopropyl, tert-butyl, 4-forfinal, pyridine-4-yl or cyclopropyl.

10. The compound or its pharmaceutically acceptable salt according to claim 2, where R19represents hydrogen or a group selected from methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tert-butyl, penttila, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, CH2(cyclopropyl), -CH2CH2NMe2, -CH(CH3)CH2HE, -C(CH3)2CH2HE, -CH2CH2HE, -CH2CH2CH2HE, 4-methylphenyl, 4-chlorphenyl, 4-trifloromethyl, 4-ftoheia, 4-methoxyphenyl, 3,4-dipthera, Tien-2-yl, -CH2(imidazol-2-yl), -CH2(imidazol-3-yl)isoxazol-3-yl, 6-oxo-1H-pyridine-2-yl, 5-methylisoxazol-3-yl, 1-methylpyrazole-4-yl, -CH2(1-methylpyrazole-4-yl), 6-methoxypyridine-3-yl, 5-herperidin-2-yl, pyridinyl-2-yl, pyrimidine-2-yl and 1H-pyrazole-3-Il.

11. The compound or its pharmaceutically acceptable salt according to claim 2, where R19represents a group selected from methyl, ethyl, propyl, cyclopropyl, cyclobutyl, -CH2CH2HE, -CH2CH2NMe2- (Me)2CH2HE and 1H-pyrazole-3-Il.

12. The compound or its pharmaceutically acceptable salt according to claim 1, selected from any of the following connections:
1-ethyl-3-[4-[4-[(3S)-3-methylmorpholin-4-yl]-6-(methylsulfonylmethyl)pyrimidine-2-yl]phenyl]urea,
1-(4-methoxyphenyl)-3-[4-[4-[(3S)-3-methylmorpholin-4-yl]-6-(methylsulfonylmethyl)pyrimidine-2-yl]phenyl]urea,
1-[4-[4-[(3S)-3-methylmorpholin-4-yl]-6-(methylsulfonylmethyl)pyrimidine-2-yl]phenyl]-3-phenylacetone,
3-[4-[4-[(3S)-3-methylmorpholin-4-yl]-6-(methylsulfonylmethyl)pyrimidine-2-yl]phenyl]-1-propane-2-rocephine,
3-(4-forfinal)-1-[4-[4-[(3S)-3-methylmorpholin-4-yl]-6-(methylsulfonylmethyl)pyrimidine-2-yl]phenyl]urea,
1-[2-fluoro-4-[4-[(3S)-3-methylmorpholin-4-yl]-6-(methylsulfonylmethyl)pyrimidine-2-yl]phenyl]-3-(4-forfinal)urea,
1-[2-fluoro-4-[4-[(3S)-3-methylmorpholin-4-yl]-6-(methylsulfonylmethyl)pyrimidine-2-yl]phenyl]-3-phenylacetone,
3-(4-forfinal)-1-[2-methoxy-4-[4-[(3S)-3-methylmorpholin-4-yl]-6-(methylsulfonylmethyl)pyrimidine-2-yl]phenyl]urea,
3-[2-methoxy-4-[4-[(3S)-3-methylmorpholin-4-yl]-6-(methylsulfonylmethyl)pyrimidine-2-yl]phenyl]-1-(4-methoxyphenyl)urea,
3-(4-forfinal)-1-[5-[4-[(3S)-3-methylmorpholin-4-yl]-6-(methylsulfonylmethyl)pyrimidine-2-yl]pyridine-2-yl]urea,
1-ethyl-3-[5-[4-[(3S)-3-methylmorpholin-4-yl]-6-(methylsulfonylmethyl)pyrimidine-2-yl]pyridine-2-yl]urea,
N-[4-[4-[(3S)-3-methylmorpholin-4-yl]-6-(methylsulfonylmethyl)pyrimidine-2-yl]phenyl]azetidin-1-carboxamid,
1-(2-methoxyethyl)-1-methyl-3-[4-[4-[(3S)-3-methylmorpholin-4-yl]-6-(methylsulfonylmethyl)pyrimidine-2-yl]phenyl]urea,
1,1-dimethyl-3-[4-[4-[(3S) - methylmorpholin-4-yl]-6-(methylsulfonylmethyl)pyrimidine-2-yl]phenyl]urea,
3-[2-methoxy-4-[4-[(3S)-3-methylmorpholin-4-yl]-6-(methylsulfonylmethyl)pyrimidine-2-yl]phenyl]-1,1-dimethyloxetane,
1-methyl-3-[4-[4-[(3S)-3-methylmorpholin-4-yl]-6-(methylsulfonylmethyl)pyrimidine-2-yl]phenyl]urea,
3-[2-fluoro-4-[4-[(3S)-3-methylmorpholin-4-yl]-6-(methylsulfonylmethyl)pyrimidine-2-yl]phenyl]-1-metalmachine,
3-[2-fluoro-4-[4-[(3S)-3-methylmorpholin-4-yl]-6-(methylsulfonylmethyl)pyrimidine-2-yl]phenyl]-1,1-dimethyloxetane,
1-[2-methyl-4-[4-[(3S)-3-methylmorpholin-4-yl]-6-(methylsulfonylmethyl)pyrimidine-2-yl]phenyl]-3-phenylacetone,
1-ethyl-3-[2-methoxy-4-[4-[(3S)-3-methylmorpholin-4-yl]-6-(methylsulfonylmethyl)pyrimidine-2-yl]phenyl]urea,
1-[2-chloro-4-[4-[(3S)-3-methylmorpholin-4-yl]-6-(methylsulfonylmethyl)pyrimidine-2-yl]phenyl]-3-phenylacetone,
1-[3-[4-[(3S)-3-methylmorpholin-4-yl]-6-(methylsulfonylmethyl)pyrimidine-2-yl]phenyl]-3-phenylacetone,
1-methyl-1-[4-[4-[(3S)-3-methylmorpholin-4-yl]-6-(methylsulfonylmethyl)pyrimidine-2-yl]phenyl]-3-phenylacetone,
1-ethyl-3-[2-fluoro-4-[4-[(3S)-3-methylmorpholin-4-yl]-6-(methylsulfonylmethyl)pyrimidine-2-yl]phenyl]urea,
N-[2-fluoro-4-[4-[(3S)-3-methylmorpholin-4-yl]-6-(methylsulfonylmethyl)pyrimidine-2-yl]phenyl]azetidin-1-carboxamid,
3-[2-fluoro-4-[4-[(3S)-3-methylmorpholin-4-yl]-6-(methylsulfonylmethyl)pyrimidine-2-yl]phenyl]-1-propane-2-rocephine,
3-[2-methoxy-4-[4-[(3S)-3-methylmorpholin-4-yl]-6-(methylsulfonylmethyl)pyrimidine-2-yl]phenyl]-1-metalmachine,
1-(2-methoxyethyl)-3-[4-[4-[(3S)-3-methylmorpholin the-4-yl]-6-(methylsulfonylmethyl)pyrimidine-2-yl]phenyl]urea,
1-(2-methoxyethyl)-3-[2-methoxy-4-[4-[(3S)-3-methylmorpholin-4-yl]-6-(methylsulfonylmethyl)pyrimidine-2-yl]phenyl]urea,
3-[2-fluoro-4-[4-[(3S)-3-methylmorpholin-4-yl]-6-(methylsulfonylmethyl)pyrimidine-2-yl]phenyl]-1-(2-methoxyethyl)-1-metalmachine,
3-[2-fluoro-4-[4-[(3S)-3-methylmorpholin-4-yl]-6-(methylsulfonylmethyl)pyrimidine-2-yl]phenyl]-1-(2-methoxyethyl)urea,
1-ethyl-3-[4-[4-(hydroxymethyl)-6-[(3S}-3-methylmorpholin-4-yl]pyrimidine-2-yl]phenyl]urea,
1-[4-[4-(hydroxymethyl)-6-[(3S)-3-methylmorpholin-4-yl]pyrimidine-2-yl]phenyl]-3-phenylacetone,
1-(4-were)-3-[4-[4-(methylsulfonylmethyl)-6-morpholine-4-Yeremey-2-yl]phenyl]urea,
3-(4-chlorophenyl)-1-[4-[4-(methylsulfonylmethyl)-6-morpholine-4-Yeremey-2-yl]phenyl]urea,
1-[4-[4-(methylsulfonylmethyl)-6-morpholine-4-yl-pyrimidine-2-yl]phenyl]-3-[4-(trifluoromethyl)phenyl]urea,
1-(3, 5dimethylphenyl)-3-[4-[4-(methylsulfonylmethyl)-6-morpholine-4-Yeremey-2-yl]phenyl]urea,
3-[2-(deformedarse)phenyl]-1-[4-[4-(methylsulfonylmethyl)-6-morpholine-4-Yeremey-2-yl]phenyl]urea,
3-(4-forfinal)-1-[4-[4-(methylsulfonylmethyl)-6-morpholine-4-Yeremey-2-yl]phenyl]urea,
3-(3-chloro-4-fluoro-phenyl)-1-[4-[4-(methylsulfonylmethyl)-6-morpholine-4-Yeremey-2-yl]phenyl]urea,
1-[4-[4-(methylsulfonylmethyl)-6-morpholine-4-yl-pyrimidine-2-yl]phenyl]-3-phenylacetone,
1-(4-methoxyphenyl)-3-[4-[4-(methylsulfonylmethyl)-6-morpholine-4-Yeremey-2-yl]phenyl]urea,
3-[4-[4-methylsulfonylmethyl)-6-morpholine-4-yl-pyrimidine-2-yl]phenyl]-1-pencilmation,
3-(3,4-differenl)-1-[4-[4-(methylsulfonylmethyl)-6-morpholine-4-Yeremey-2-yl]phenyl]urea,
3-cyclohexyl-1-[4-[4-(methylsulfonylmethyl)-6-morpholine-4-Yeremey-2-yl]phenyl]urea,
1-ethyl-3-[4-[4-(methylsulfonylmethyl)-6-morpholine-4-Yeremey-2-yl]phenyl]urea,
3-[4-[4-(methylsulfonylmethyl)-6-morpholine-4-Yeremey-2-yl]phenyl]-1-propylbetaine,
1-(3-ethylphenyl)-3-[4-[4-(methylsulfonylmethyl)-6-morpholine-4-yl-pyrimidine-2-yl]phenyl]urea,
3-(2-furylmethyl)-1-[4-[4-(methylsulfonylmethyl)-6-morpholine-4-yl-pyrimidine-2-yl]phenyl]urea,
1-[4-[4-(methylsulfonylmethyl)-6-morpholine-4-yl-pyrimidine-2-yl]phenyl]-3-(2-thiophene-2-retil)urea,
1-[4-[4-(methylsulfonylmethyl)-6-morpholine-4-yl-pyrimidine-2-yl]phenyl]-3-thiophene-2-yl-urea,
3-cyclopropyl-1-[4-[4-(methylsulfonylmethyl)-6-morpholine-4-Yeremey-2-yl]phenyl]urea,
1-[4-[4-(methylsulfonylmethyl)-6-morpholine-4-yl-pyrimidine-2-yl]phenyl]-3-tert-butylation,
N-[2-[[4-[4-(methylsulfonylmethyl)-6-morpholine-4-Yeremey-2-yl]phenyl]carbamoylating]ethyl]acetamide", she
1-(2-dimethylaminoethyl)-1-methyl-3-[4-[4-(methylsulfonylmethyl)-6-morpholine-4-Yeremey-2-yl]phenyl]urea,
3-(1H-imidazol-2-ylmethyl)-1-[4-[4-(methylsulfonylmethyl)-6-morpholine-4-Yeremey-2-yl]phenyl]urea,
1-cyclopropyl-1-methyl-3-[4-[4-(methylsulfonylmethyl)-6-morpholine-4-Yeremey-2-yl]phenyl]urea,
1-[4-[4-[(3S)-3-methylmorpholin-4-yl]-6-(methylsulfonylmethyl)pyrimi the Jn-2-yl]phenyl]-3-(2-methylpropyl)urea,
1-[3-[4-[(3S)-3-methylmorpholin-4-yl]-6-(methylsulfonylmethyl)pyrimidine-2-yl]phenyl]-3-propan-2-rocephine,
3-ethyl-1-[3-[4-[(3S)-3-methylmorpholin-4-yl]-6-(methylsulfonylmethyl)pyrimidine-2-yl]phenyl]urea,
1-[2-chloro-4-[4-[(3S)-3-methylmorpholin-4-yl]-6-(methylsulfonylmethyl)pyrimidine-2-yl]phenyl]-3-atilmotin,
3-methyl-1-[2-methyl-4-[4-[(3S)-3-methylmorpholin-4-yl]-6-(methylsulfonylmethyl)pyrimidine-2-yl]phenyl]urea,
3-[4-[4-(hydroxymethyl)-6-[(3S)-3-methylmorpholin-4-yl]pyrimidine-2-yl]phenyl]-1,1-dimethyloxetane,
N-[2-[[6-[(3S)-3-methylmorpholin-4-yl]-2-[4-(phenylcarbonylamino)phenyl]pyrimidine-4-yl]methylsulphonyl]ethyl]acetamide", she
1-[4-[4-(benzosulfimide)-6-[(3S)-3-methylmorpholin-4-yl]pyrimidine-2-yl]phenyl]-3-phenylacetone,
3-[4-[4-(cyanometallates)-6-[(3S)-3-methylmorpholin-4-yl]pyrimidine-2-yl]phenyl]-1,1-dimethyloxetane,
1,1-dimethyl-3-[4-[4-[(3S)-3-methylmorpholin-4-yl]-6-(propane-2-ylsulphonyl)pyrimidine-2-yl]phenyl]urea,
3-[4-[4-(benzosulfimide)-6-[(3S)-3-methylmorpholin-4-yl]pyrimidine-2-yl]phenyl]-1,1-dimethyloxetane,
N-[2-[[2-[4-(dimethylcarbamoyl)phenyl]-6-[(3S)-3-ethylmorpholine-4-yl]pyrimidine-4-yl]methylsulphonyl]ethyl]acetamide", she
2-[[2-[4-(dimethylcarbamoyl)phenyl]-6-[(3S)-3-methylmorpholin-4-yl]pyrimidine-4-yl]methylsulphonyl]ndimethylacetamide,
1-[4-[4-(hydroxymethyl)-6-[(3S)-3-methylmorpholin-4-yl]pyrimidine-2-yl]phenyl]-3-metalmachine,
1-[4-[4-(cyclohexylsulfamate)-6-[(3S)-3-methylmorpholin-4-yl]p is rimidine-2-yl]phenyl]-3-metalmachine,
1-[4-[4-(benzosulfimide)-6-[(3S)-3-methylmorpholin-4-yl]pyrimidine-2-yl]phenyl]-3-metalmachine,
1-[4-[4-[(4-forfinal)sulfanilyl]-6-[(3S)-3-methylmorpholin-4-yl]pyrimidine-2-yl]phenyl]-3-metalmachine,
N-[4-[[2-[4-(methylcarbamoyl)phenyl]-6-[(3S)-3-methylmorpholin-4-yl]pyrimidine-4-yl]methylsulphonyl]phenyl]acetamide", she
3-methyl-1-[4-[4-[(3S)-3-methylmorpholin-4-yl]-6-(propane-2-ylsulphonyl)pyrimidine-2-yl]phenyl]urea,
1-[4-[4-(2-hydroxyethylaminomethyl)-6-[(3S)-3-methylmorpholin-4-yl]pyrimidine-2-yl]phenyl]-3-methyl-urea,
3-methyl-1-[4-[4-[(3S)-3-methylmorpholin-4-yl]-6-(pyridine-4-ylsulphonyl)pyrimidine-2-yl]phenyl]urea,
1-[4-[4-(cyclohexylsulfamate)-6-[(3S)-3-methylmorpholin-4-yl]pyrimidine-2-yl]phenyl]-3-metalmachine,
3-methyl-1-[4-[4-[(3S)-3-methylmorpholin-4-yl]-6-(phenylsulfanyl)pyrimidine-2-yl]phenyl]urea,
1-[4-[4-[(4-forfinal)sulfanilyl]-6-[(3S)-3-methylmorpholin-4-yl]pyrimidine-2-yl]phenyl]-3-metalmachine,
N-[4-[[2-[4-(methylcarbamoyl)phenyl]-6-[(3S)-3-methylmorpholin-4-yl]pyrimidine-4-yl]methylsulfinyl]phenyl]acetamide", she
3-methyl-1-[4-[4-[(3S)-3-methylmorpholin-4-yl]-6-(propane-2-ylsulphonyl)pyrimidine-2-yl]phenyl]urea,
1-[4-[4-(2-hydroxyethylaminomethyl)-6-[(3S)-3-methylmorpholin-4-yl]pyrimidine-2-yl]phenyl]-3-metalmachine,
3-methyl-1-[4-[4-[(3S)-3-methylmorpholin-4-yl]-6-(pyridine-4-ylsulphonyl)pyrimidine-2-yl]phenyl]urea,
3-[4-[4-(benzosulfimide)-6-Mohali the-4-Yeremey-2-yl]phenyl]-1-metalmachine,
3-[4-[4-(benzosulfimide)-6-morpholine-4-Yeremey-2-yl]phenyl]-1-atilmotin,
1-[4-[4-(benzosulfimide)-6-morpholine-4-Yeremey-2-yl]phenyl]-3-cyclopropylamino,
3-[4-[4-(benzosulfimide)-6-morpholine-4-yl-pyrimidine-2-yl]phenyl]-1-(2-dimethylaminoethyl)urea,
3-[4-[4-(benzosulfimide)-6-morpholine-4-yl-pyrimidine-2-yl]phenyl]-1-(1-methyl-4-piperidyl)urea,
3-[4-[4-(benzosulfimide)-6-morpholine-4-yl-pyrimidine-2-yl]phenyl]-1-(2-methoxyethyl)urea,
3-[4-[4-(benzosulfimide)-6-[(3S)-3-methylmorpholin-4-yl]pyrimidine-2-yl]phenyl]-1-ethyl-urea,
1-[4-[4-(benzosulfimide)-6-[(3S)-3-methylmorpholin-4-yl]pyrimidine-2-yl]phenyl]-3-cyclopropylamino,
1-[4-[4-(benzosulfimide)-6-[(3S)-3-methylmorpholin-4-yl]pyrimidine-2-yl]phenyl]-3-(2-dimethylaminoethyl)urea,
1-[4-[4-(benzosulfimide)-6-[(3S)-3-methylmorpholin-4-yl]pyrimidine-2-yl]phenyl]-3-(1-methyl-4-piperidyl)urea,
1-[4-[4-(benzosulfimide)-6-[(3S)-3-methylmorpholin-4-yl]pyrimidine-2-yl]phenyl]-3-(2-methoxyethyl)urea,
3-methyl-1-[4-[4-morpholine-4-yl-6-(propane-2-ylsulphonyl)pyrimidine-2-yl]phenyl]urea,
1-ethyl-3-[4-[4-morpholine-4-yl-6-(propane-2-ylsulphonyl)pyrimidine-2-yl]phenyl]urea,
3-cyclopropyl-1-[4-[4-morpholine-4-yl-6-(propane-2-ylsulphonyl)pyrimidine-2-yl]phenyl]urea,
3-(2-dimethylaminoethyl)-1-[4-[4-morpholine-4-yl-6-(propane-2-ylsulphonyl)pyrimidine-2-yl]phenyl]urea, 3-(1-methyl-4-piperidyl)-1-[4-[4-morpholine-4-yl-6-(propane-2-ylsulphonyl)pyrimidine-2-yl]phenyl]urea,
3-(2-methoxyethyl)-1-[4-[4-morpholine-4-yl-6-(propane-2-ylsulphonyl)pyrimidine-2-yl]phenyl]urea,
1-ethyl-3-[4-[4-[(3S)-3-methylmorpholin-4-yl]-6-(propane-2-ylsulphonyl)pyrimidine-2-yl]phenyl]urea,
3-cyclopropyl-1-[4-[4-[(3S)-3-methylmorpholin-4-yl]-6-(propane-2-ylsulphonyl)pyrimidine-2-yl]phenyl]urea,
3-(2-dimethylaminoethyl)-1-[4-[4-[(3S)-3-methylmorpholin-4-yl]-6-(propane-2-ylsulphonyl)pyrimidine-2-yl]phenyl]urea,
1-[4-[4-[(3S)-3-methylmorpholin-4-yl]-6-(propane-2-ylsulphonyl)pyrimidine-2-yl]phenyl]-3-(1-methyl-4-piperidyl)urea,
3-(2-methoxyethyl)-1-[4-[4-[(3S)-3-methylmorpholin-4-yl]-6-(propane-2-ylsulphonyl)pyrimidine-2-yl]phenyl]urea,
3-methyl-1-[4-[4-(2-methylsulfonylamino-2-yl)-6-morpholine-4-Yeremey-2-yl]phenyl]urea,
1-ethyl-3-[4-[4-(2-methylsulfonylamino-2-yl)-6-morpholine-4-Yeremey-2-yl]phenyl]urea,
3-cyclopropyl-1-[4-[4-(2-methylsulfonylamino-2-yl)-6-morpholine-4-Yeremey-2-yl]phenyl]urea,
3-(2-dimethylaminoethyl)-1-[4-[4-(2-methylsulfonylamino-2-yl)-6-morpholine-4-Yeremey-2-yl]phenyl]urea,
3-(1-methyl-4-piperidyl)-1-[4-[4-(2-methylsulfonylamino-2-yl)-6-morpholine-4-Yeremey-2-yl]phenyl]urea,
3-(2-methoxyethyl)-1-[4-[4-(2-methylsulfonylamino-2-yl)-6-morpholine-4-yl-pyrimidine-2-yl]phenyl]urea,
3-methyl-1-[4-[4-[(3S)-3-methylmorpholin-4-yl]-6-(2-what ethylsulfonyl-2-yl)pyrimidine-2-yl]phenyl]urea,
1-ethyl-3-[4-[4-[(3S)-3-methylmorpholin-4-yl]-6-(2-methylsulfonylamino-2-yl)pyrimidine-2-yl]phenyl]urea,
3-cyclopropyl-1-[4-[4-[(3S)-3-methylmorpholin-4-yl]-6-(2-methylsulfonylamino-2-yl)pyrimidine-2-yl]phenyl]urea,
3-(2-dimethylaminoethyl)-1-[4-[4-[(3S)-3-methylmorpholin-4-yl]-6-(2-methylsulfonylamino-2-yl)pyrimidine-2-yl]phenyl]urea,
1-[4-[4-[(3S)-3-methylmorpholin-4-yl]-6-(2-methylsulfonylamino-2-yl)pyrimidine-2-yl]phenyl]-3-(1-methyl-4-piperidyl)urea,
3-(2-methoxyethyl)-1-[4-[4-[(3S)-3-methylmorpholin-4-yl]-6-(2-methylsulfinylpropyl-2-1)pyrimidine-2-yl]phenyl]urea,
1-[4-[4-[(3S)-3-methylmorpholin-4-yl]-6-(methylsulfonylmethyl)pyrimidine-2-yl]phenyl]-3-(1,2-oxazol-3-yl)urea,
1-[4-[4-[(3S)-3-methylmorpholin-4-yl]-6-(methylsulfonylmethyl)pyrimidine-2-yl]phenyl]-3-pyrimidine-2-yl-urea,
1-(2,6-dimetilfenil)-3-[4-[4-[(3S)-3-methylmorpholin-4-yl]-6-(methylsulfonylmethyl)pyrimidine-2-yl]phenyl]urea,
1-[4-[4-[(3S)-3-methylmorpholin-4-yl]-6-(methylsulfonylmethyl)pyrimidine-2-yl]phenyl]-3-(6-oxo-1H-pyridine-2-yl)urea,
3-[4-[4-[(3S)-3-methylmorpholin-4-yl]-6-(methylsulfonylmethyl)pyrimidine-2-yl]phenyl]-1-(5-methyl-1,2-oxazol-3-yl)urea,
3-[4-[4-[(3S)-3-methylmorpholin-4-yl]-6-(methylsulfonylmethyl)pyrimidine-2-yl]phenyl]-1-(5-methyl-1,2-oxazol-4-yl)urea,
1-[4-[4-[(3S)-3-methylmorpholin-4-yl]-6-(methylsulfonylmethyl)pyrimidine-2-yl]phenyl]-3-(1-methylpyrazole-4-yl)urea,
1-[4-[4-[(3S)-3-methylmorpholin-4-yl]-6-(methylsulfonylmethyl)pyrimidine--yl]phenyl]-3-(2-oxo-1H-pyridin-4-yl)urea,
3-[4-[4-[(3S)-3-methylmorpholin-4-yl]-6-(methylsulfonylmethyl)pyrimidine-2-yl]phenyl]-1-(1,3,5-trimethylpyrazole-4-yl)urea,
1-(3,5-dimethyl-1H-pyrazole-4-yl)-3-[4-[4-[(3S)-3-methylmorpholin-4-yl]-6-(methylsulfonylmethyl)pyrimidine-2-yl]phenyl]urea,
3-methyl-1-[1-[4-[(3S)-3-methylmorpholin-4-yl]-6-(methylsulfonylmethyl)pyrimidine-2-yl]-4-piperidyl]urea,
1-ethyl-3-[1-[4-[(3S)-3-methylmorpholin-4-yl]-6-(methylsulfonylmethyl)pyrimidine-2-yl]-4-piperidyl]urea,
1-[4-[4-[(3S)-3-methylmorpholin-4-yl]-6-(methylsulfonylmethyl)pyrimidine-2-yl]phenyl]-3-(2-pyridin-2-retil)urea,
1-[4-[4-[(3S)-3-methylmorpholin-4-yl]-6-(methylsulfonylmethyl)pyrimidine-2-yl]phenyl]-3-(pyridine-3-ylmethyl)urea,
3-[2-(1H-imidazol-4-yl)ethyl]-1-[4-[4-[(3S)-3-methylmorpholin-4-yl]-6-(methylsulfonylmethyl)pyrimidine-2-yl]phenyl]urea,
3-[4-[4-[(3S)-3-methylmorpholin-4-yl]-6-(methylsulfonylmethyl)pyrimidine-2-yl]phenyl]-1-[(5-methylpyridin-2-yl)methyl]urea,
1-[4-[4-[(3S)-3-methylmorpholin-4-yl]-6-(methylsulfonylmethyl)pyrimidine-2-yl]phenyl]-3-(pyridine-2-ylmethyl)urea,
1-[4-[4-[(3S)-3-methylmorpholin-4-yl]-6-(methylsulfonylmethyl)pyrimidine-2-yl]phenyl]-3-(pyridine-4-ylmethyl)urea,
3-[(4-methoxyphenyl)methyl]-1-[4-[4-[(3S)-3-methylmorpholin-4-yl]-6-(methylsulfonylmethyl)pyrimidine-2-yl]phenyl]urea,
1-[4-[4-[(3S)-3-methylmorpholin-4-yl]-6-(methylsulfonylmethyl)pyrimidine-2-yl]phenyl]-3-[(1-methylpyrazole-4-yl)methyl]urea,
3-[4-[4-[(3S)-3-methylmorpholin-4-yl]-6-(methylsulfonyl the l)pyrimidine-2-yl]phenyl]-1-[(5-methyl-1,2-oxazol-3-yl)methyl]urea,
3-[(3-dimethylaminophenyl)methyl]-1-[4-[4-[(3S)-3-methylmorpholin-4-yl]-6-(methylsulfonylmethyl)pyrimidine-2-yl]phenyl]urea,
1-[4-[4-[(3S)-3-methylmorpholin-4-yl]-6-(methylsulfonylmethyl)pyrimidine-2-yl]phenyl]-3-(1,3-thiazol-5-ylmethyl)urea,
3-methyl-1-[1-[4-[(3S)-3-methylmorpholin-4-yl]-6-(methylsulfonylmethyl)pyrimidine-2-yl]pyrazole-3-yl]urea,
1-ethyl-3-[1-[4-[(3S)-3-methylmorpholin-4-yl]-6-(methylsulfonylmethyl)pyrimidine-2-yl]pyrazole-3-yl]urea,
3-cyclopropyl-1-[1-[4-[(3S)-3-methylmorpholin-4-yl]-6-(methylsulfonylmethyl)pyrimidine-2-yl]pyrazole-3-yl]urea,
3-methyl-1-[1-[4-[(3S)-3-methylmorpholin-4-yl]-6-(2-methylsulfonylamino-2-yl)pyrimidine-2-yl]-4-piperidyl]urea,
1-ethyl-3-[1-[4-[(3S)-3-methylmorpholin-4-yl]-6-(2-methylsulfonylamino-2-yl)pyrimidine-2-yl]-4-piperidyl]urea,
3-cyclopropyl-1-[1-[4-[(3S)-3-methylmorpholin-4-yl]-6-(2-methylsulfonylamino-2-yl)pyrimidine-2-yl]-4-piperidyl]urea,
1-[1-[4-[(3S)-3-methylmorpholin-4-yl]-6-(2-methylsulfonylamino-2-yl)pyrimidine-2-yl]-4-piperidyl]-3-[(1-methylpyrazole-4-yl)methyl]urea,
3-cyclopropyl-1-[5-[4-[(3S)-3-methylmorpholin-4-yl]-6-(methylsulfonylmethyl)pyrimidine-2-yl]pyridine-2-yl]urea,
1-[4-[4-[(3S)-3-methylmorpholin-4-yl]-6-(2-methylsulfonylamino-2-yl)pyrimidine-2-yl]phenyl]-3-(1,2-oxazol-3-yl)urea,
3-[4-[4-[(3S)-3-methylmorpholin-4-yl]-6-(2-methylsulfonylamino-2-yl)pyrimidine-2-yl]phenyl]-1-(5-methyl-1,2-oxazol-3-yl)urea,
1-[4-[4-[(3S)-3-methylmorpholin-4-yl]-6-(2-matilal phenylpropan-2-yl)pyrimidine-2-yl]phenyl]-3-pyrimidine-2-yl-urea,
1-[4-[4-[(3S)-3-methylmorpholin-4-yl]-6-(2-methylsulfonylamino-2-yl)pyrimidine-2-yl]phenyl]-3-(1H-pyrazole-3-yl)urea,
1-[4-[4-[(3S)-3-methylmorpholin-4-yl]-6-(2-methylsulfonylamino-2-yl)pyrimidine-2-yl]phenyl]-3-phenylacetone,
3-(6-methoxypyridine-3-yl)-1-[4-[4-[(3S)-3-methylmorpholin-4-yl]-6-(2-methylsulfonylamino-2-yl)pyrimidine-2-yl]phenyl]urea,
3-(5-herperidin-2-yl)-1-[4-[4-[(3S)-3-methylmorpholin-4-yl]-6-(2-methylsulfonylamino-2-yl)pyrimidine-2-yl]phenyl]urea,
1-[5-[4-[(3S)-3-methylmorpholin-4-yl]-6-(2-methylsulfonylamino-2-yl)pyrimidine-2-yl]pyrimidine-2-yl]-3-[(1-methylpyrazole-4-yl)methyl]urea,
3-cyclopropyl-1-[4-[4-[(3S)-3-methylmorpholin-4-yl]-6-(methylsulfonylmethyl)pyrimidine-2-yl]phenyl]urea,
1-[2,6-debtor-4-[4-[(3S)-3-methylmorpholin-4-yl]-6-(2-methylsulfonylamino-2-yl)pyrimidine-2-yl]phenyl]-3-metalmachine,
3-[2,6-debtor-4-[4-[(3S)-3-methylmorpholin-4-yl]-6-(2-methylsulfonylamino-2-yl)pyrimidine-2-yl]phenyl]-1-atilmotin,
3-cyclopropyl-1-[2,6-debtor-4-[4-[(3S)-3-methylmorpholin-4-yl]-6-(2-methylsulfonylamino-2-yl)pyrimidine-2-yl]phenyl]urea,
1-[2,6-debtor-4-[4-[(3S)-3-methylmorpholin-4-yl]-6-(2-methylsulfonylamino-2-yl)pyrimidine-2-yl]phenyl]-3-[(1-methylpyrazole-4-yl)methyl]urea,
1-ethyl-3-[5-[4-[(3S)-3-methylmorpholin-4-yl]-6-(2-methylsulfinylpropyl-
2-yl)pyrimidine-2-yl]pyrimidine-2-yl]urea,
3-cyclopropyl-1-[5-[4-[(3S)-3-methylmorpholin-4-yl]-6-(2-methylsulfonylamino-2-yl)pyrimidine-2-yl]pyrimidine-2-yl]urea is,
3-methyl-1-[5-[4-[(3S)-3-methylmorpholin-4-yl]-6-(2-methylsulfonylamino-2-yl)pyrimidine-2-yl]pyridine-2-yl]urea,
1-ethyl-3-[5-[4-[(3S)-3-methylmorpholin-4-yl]-6-(2-methylsulfinylpropyl-
2-yl)pyrimidine-2-yl]pyridine-2-yl]urea,
3-cyclopropyl-1-[5-[4-[(3S)-3-methylmorpholin-4-yl]-6-(2-methylsulfonylamino-2-yl)pyrimidine-2-yl]pyridine-2-yl]urea,
3-[4-[4-[(3S)-3-methylmorpholin-4-yl]-6-(2-methylsulfonylamino-2-yl)pyrimidine-2-yl]phenyl]-1-propylbetaine,
1-[4-[4-[(3S)-3-methylmorpholin-4-yl]-6-(2-methylsulfonylamino-2-yl)pyrimidine-2-yl]phenyl]-3-propan-2-yl-urea,
3-cyclobutyl-1-[4-[4-[(3S)-3-methylmorpholin-4-yl]-6-(2-methylsulfonylamino-2-yl)pyrimidine-2-yl]phenyl]urea,
3-(1-hydroxy-2-methyl-propane-2-yl)-1-[4-[4-[(3S)-3-methylmorpholin-4-yl]-
6-(2-methylsulfonylamino-2-yl)pyrimidine-2-yl]phenyl]urea,
1-[4-[4-[(3S)-3-methylmorpholin-4-yl]-6-(2-methylsulfonylamino-2-yl)pyrimidine-2-yl]phenyl]-3-(pyridine-3-ylmethyl)urea,
3-[(2R)-1-hydroxypropan-2-yl]-1-[4-[4-[(3S)-3-methylmorpholin-4-yl]-6-(2-methylsulfonylamino-2-yl)pyrimidine-2-yl]phenyl]urea,
3-(cyclopropylmethyl)-1-[4-[4-[(3S)-3-methylmorpholin-4-yl]-6-(2-methylsulfonylamino-2-yl)pyrimidine-2-yl]phenyl]urea,
1-[4-[4-[(3S)-3-methylmorpholin-4-yl]-6-(2-methylsulfonylamino-2-yl)pyrimidine-2-yl]phenyl]-3-(pyridine-4-ylmethyl)urea,
3-(3-hydroxypropyl)-1-[4-[4-[(3S)-3-methylmorpholin-4-yl]-6-(2-methylsulfonylamino-2-yl)pyrimidine-2-yl]phenyl]urea,
1-[4-[4-[(3S)-3-metil Holin-4-yl]-6-(2-methylsulfonylamino-2-yl)pyrimidine-2-yl]phenyl]-3-(2-methylpropyl)urea,
3-(1H-imidazol-2-ylmethyl)-1-[4-[4-[(3S)-3-methylmorpholin-4-yl]-6-(2-methylsulfonylamino-2-yl)pyrimidine-2-yl]phenyl]urea,
1-[4-[4-[(3S)-3-methylmorpholin-4-yl]-6-(2-methylsulfonylamino-2-yl)pyrimidine-2-yl]phenyl]-3-[(1-methylpyrazole-4-yl)methyl]urea,
3-[4-[4-[(3S)-3-methylmorpholin-4-yl]-6-(2-methylsulfonylamino-2-yl)pyrimidine-2-yl]phenyl]-1-[(5-methyl-1,2-oxazol-3-yl)methyl]urea,
1-[4-[4-[(3S)-3-methylmorpholin-4-yl]-6-(2-methylsulfonylamino-2-yl)pyrimidine-2-yl]phenyl]-3-(1-pyridine-3-retil)urea,
1-[4-[4-[(3S)-3-methylmorpholin-4-yl]-6-(2-methylsulfonylamino-2-yl)pyrimidine-2-yl]phenyl]-3-(1H-pyrazole-3-ylmethyl)urea,
1-[4-[4-[(3S)-3-methylmorpholin-4-yl]-6-(2-methylsulfonylamino-2-yl)pyrimidine-2-yl]phenyl]-3-[(1-methylpyrazole-3-yl)methyl]urea,
1,1-dimethyl-3-[4-[4-[(3S)-3-methylmorpholin-4-yl]-6-(2-methylsulfonylamino-2-yl)pyrimidine-2-yl]phenyl]urea,
N-[4-[4-[(3S)-3-methylmorpholin-4-yl]-6-(2-methylsulfonylamino-2-yl)pyrimidine-2-yl]phenyl]morpholine-4-carboxamide,
4-hydroxy-N-[4-[4-[(3S)-3-methylmorpholin-4-yl]-6-(2-methylsulfonylamino-2-yl)pyrimidine-2-yl]phenyl]piperidine-1-carboxamide,
3-hydroxy-N-[4-[4-[(3S)-3-methylmorpholin-4-yl]-6-(2-methylsulfonylamino-2-yl)pyrimidine-2-yl]phenyl]piperidine-1-carboxamide,
N-[4-[4-[(3S)-3-methylmorpholin-4-yl]-6-(2-methylsulfonylamino-2-yl)pyrimidine-2-yl]phenyl]azetidin-1-carboxamid,
3-hydroxy-N-[4-[4-[(3S)-3-methylmorpholin-4-yl]-6-(2-methylsulfonylamino-2-yl)pyrimidine-2-yl]phenylaziridine-1-carboxamid,
1-cyclopropyl-1-methyl-3-[4-[4-[(3S)-3-methylmorpholin-4-yl]-6-(2-methylsulfonylamino-2-yl)pyrimidine-2-yl]phenyl]urea,
3-methyl-1-[5-[4-[(3S)-3-methylmorpholin-4-yl]-6-(2-methylsulfonylamino-2-yl)pyrimidine-2-yl]pyrimidine-2-yl]urea,
1-[5-[4-[(3S)-3-methylmorpholin-4-yl]-6-(2-methylsulfonylamino-2-yl)pyrimidine-2-yl]pyridine-2-yl]-3-[(1-methylpyrazole-4-yl)methyl]urea,
3-(2-hydroxyethyl)-1-[4-[4-[(3S)-3-methylmorpholin-4-yl]-6-(2-methylsulfonylamino-2-yl)pyrimidine-2-yl]phenyl]urea,
1-[1-[4-[(35)-3-methylmorpholin-4-yl]-6-(methylsulfonylmethyl)pyrimidine-2-yl]pyrazole-3-yl]-3-phenylacetone,
3-(4-methoxyphenyl)-1-[1-[4-[(3S)-3-methylmorpholin-4-yl]-6-(methylsulfonylmethyl)pyrimidine-2-yl]pyrazole-3-yl]urea,
3-(4-forfinal)-1-[1-[4-[(3S)-3-methylmorpholin-4-yl]-6-(methylsulfonylmethyl)pyrimidine-2-yl]pyrazole-3-yl]urea,
N-methyl-2-[[2-[4-(methylcarbamoyl)phenyl]-6-[(3S)-3-methylmorpholin-4-yl]pyrimidine-4-yl]methylsulphonyl]ndimethylacetamide,
2-[[2-[4-(methylcarbamoyl)phenyl]-6-[(3S)-3-methylmorpholin-4-yl]pyrimidine-4-yl]methylsulphonyl]ndimethylacetamide,
N-[2-[[2-[4-(methylcarbamoyl)phenyl]-6-[(3S)-3-methylmorpholin-4-yl]pyrimidine-4-yl]methylsulphonyl]ethyl]acetamide", she
N-methyl-2-[[2-[4-(methylcarbamoyl)phenyl]-6-[(3S)-3-methylmorpholin-4-yl]pyrimidine-4-yl]methylsulfanyl]ndimethylacetamide,
2-[[2-[4-(methylcarbamoyl)phenyl]-6-[(3S)-3-methylmorpholin-4-yl]pyrimidine-4-yl]methylsulfanyl]ndimethylacetamide,
N-[2-[[2-[4-(methylcarbamoyl)phenyl]-6-[(3S)3-methylmorpholin-4-yl]pyrimidine-4-yl]methylsulfanyl]ethyl]acetamide", she
1-[4-[4-[(3S)-3-methylmorpholin-4-yl]-6-(morpholine-4-ylmethyl)pyrimidine-2-yl]phenyl]-3-phenylacetone,
1-[4-[4-[(3S)-3-methylmorpholin-4-yl]-6-(phenoxymethyl)pyrimidine-2-yl]phenyl]-3-phenylacetone,
1-[4-[4-[(3S)-3-methylmorpholin-4-yl]-6-[(2-oxopyrrolidin-3-yl)sulfanilyl]pyrimidine-2-yl]phenyl]-3-phenylacetone,
1-[4-[4-[(3S)-3-methylmorpholin-4-yl]-6-[(2-oxopyrrolidin-3-yl)sulfanilyl]pyrimidine-2-yl]phenyl]-3-phenylacetone,
1-[4-[4-(anilinomethyl)-6-[(3S)-3-methylmorpholin-4-yl]pyrimidine-2-yl]phenyl]-3-phenylacetone,
1-[4-[4-[(3S)-3-methylmorpholin-4-yl]-6-[(4-methylpiperazin-1-yl)methyl]pyrimidine-2-yl]phenyl]-3-phenylacetone,
1-[4-[4-[(cyclopropylamino)methyl]-6-[(3S)-3-methylmorpholin-4-yl]pyrimidine-2-yl]phenyl]-3-phenyl-urea,
1-[4-[4-[(3S)-3-methylmorpholin-4-yl]-6-[[(1-methyl-4-piperidyl)amino]methyl]pyrimidine-2-yl]phenyl]-3-phenylacetone,
1-[4-[4-[(cyclopropylamino)methyl]-6-[(3S)-3-methylmorpholin-4-yl]pyrimidine-2-yl]phenyl]-3-phenylacetone,
1-[4-[4-[(3S)-3-methylmorpholin-4-yl]-6-[(1-methyl-4-piperidyl)oxymethyl]pyrimidine-2-yl]phenyl]-3-phenyl-urea,
1-[4-[4-(methoxymethyl)-6-[(3S)-3-methylmorpholin-4-yl]pyrimidine-2-yl]phenyl]-3-phenylacetone,
3-methyl-1-[4-[4-[(1-Mei-2-yl)sulfanilyl]-6-[(3S)-3-methylmorpholin-4-yl]pyrimidine-2-yl]phenyl]urea,
1-[4-[4-[(2-chlorophenyl)sulfanilyl]-6-[(3S)-3-methylmorpholin-4-yl]pyrimidine-2-yl]phenyl]-3-metalmachine,
1-[4-[4-[(2-methoxyphenyl)sulfanilyl]-6-[(3S)-3-methylmorpholin-4-yl]pyrim the DIN-2-yl]phenyl]-3-metalmachine,
1-[4-[4-(1H-imidazol-2-ylsulphonyl)-6-[(3S)-3-methylmorpholin-4-yl]pyrimidine-2-yl]phenyl]-3-methyl-urea,
1-[4-[4-[(4-AMINOPHENYL)sulfanilyl]-6-[(3S)-3-methylmorpholin-4-yl]pyrimidine-2-yl]phenyl]-3-metalmachine,
3-methyl-1-[4-[4-[(3S)-3-methylmorpholin-4-yl]-6-[(2-were)sulfanilyl]pyrimidine-2-yl]phenyl]urea,
3-methyl-1-[4-[4-[(3S)-3-methylmorpholin-4-yl]-6-(pyridine-2-ylsulphonyl)pyrimidine-2-yl]phenyl]urea,
3-methyl-1-[4-[4-[(3S)-3-methylmorpholin-4-yl]-6-(1,3-thiazol-2-ylsulphonyl)pyrimidine-2-yl]phenyl]urea,
3-methyl-1-[4-[4-[(3S)-3-methylmorpholin-4-yl]-6-[(4-methyl-1,3-thiazol-2-yl)sulfanilyl]pyrimidine-2-yl]phenyl]urea,
3-methyl-1-[4-[4-[(1-Mei-2-yl)sulfanilyl]-6-[(3S)-3-methylmorpholin-4-yl]pyrimidine-2-yl]phenyl]urea,
1-[4-[4-[(2-chlorophenyl)sulfanilyl]-6-[(3S)-3-methylmorpholin-4-yl]pyrimidine-2-yl]phenyl]-3-metalmachine,
1-[4-[4-[(2-methoxyphenyl)sulfanilyl]-6-[(3S)-3-methylmorpholin-4-yl]pyrimidine-2-yl]phenyl]-3-metalmachine,
1-[4-[4-(1H-imidazol-2-ylsulphonyl)-6-[(3S)-3-methylmorpholin-4-yl]pyrimidine-2-yl]phenyl]-3-metalmachine,
1-[4-[4-[(4-AMINOPHENYL)sulfanilyl]-6-[(3S)-3-methylmorpholin-4-yl]pyrimidine-2-yl]phenyl]-3-metalmachine,
3-methyl-1-[4-[4-[(3S)-3-methylmorpholin-4-yl]-6-[(2-were)sulfanilyl]pyrimidine-2-yl]phenyl]urea,
3-methyl-1-[4-[4-[(3S)-3-methylmorpholin-4-yl]-6-(pyridine-2-ylsulphonyl)pyrimidine-2-yl]phenyl]urea,
3-methyl-1-[4-[4-[(3S)-3-ethylmorpholine-4-yl]-6-(1,3-thiazol-2-ylsulphonyl)pyrimidine-2-yl]phenyl]urea,
3-methyl-1-[4-[4-[(3S)-3-methylmorpholin-4-yl]-6-[(4-methyl-1,3-thiazol-2-yl)sulfanilyl]pyrimidine-2-yl]phenyl]urea,
[4-[4-(methylsulfonylmethyl)-6-morpholine-4-yl-pyrimidine-2-yl]phenyl]urea,
1-[4-[4-(methylsulfonylmethyl)-6-morpholine-4-yl-pyrimidine-2-yl]phenyl]-3-(1,2-oxazol-3-yl)urea,
1-(5-methyl-1,2-oxazol-3-yl)-3-[4-[4-(methylsulfonylmethyl)-6-morpholine-4-Yeremey-2-yl]phenyl]urea,
1-(1-methylpyrazole-3-yl)-3-[4-[4-(methylsulfonylmethyl)-6-morpholine-4-Yeremey-2-yl]phenyl]urea,
3-(1-hydroxypropan-2-yl)-1-[4-[4-[(3S)-3-methylmorpholin-4-yl]-6-(methylsulfonylmethyl)pyrimidine-2-yl]phenyl]urea,
3-(3-dimethylaminopropyl)-1-[4-[4-[(3S)-3-methylmorpholin-4-yl]-6-(methylsulfonylmethyl)pyrimidine-2-yl]phenyl]urea,
3-(3-methoxypropyl)-1-[4-[4-[(3S)-3-methylmorpholin-4-yl]-6-(methylsulfonylmethyl)pyrimidine-2-yl]phenyl]urea,
N-[4-[4-[(3S)-3-methylmorpholin-4-yl]-6-(methylsulfonylmethyl)pyrimidine-2-yl]phenyl]pyrrolidin-1-carboxamid,
N-[4-[4-[(3S)-3-methylmorpholin-4-yl]-6-(methylsulfonylmethyl)pyrimidine-2-yl]phenyl]morpholine-4-carboxamide,
4-hydroxy-N-[4-[4-[(3S)-3-methylmorpholin-4-yl]-6-(methylsulfonylmethyl)pyrimidine-2-yl]phenyl]piperidine-1-carboxamide,
1-[4-[4-[(3S)-3-methylmorpholin-4-yl]-6-(methylsulfonylmethyl)pyrimidine-2-yl]phenyl]-3-tert-butylation,
3-(2-dimethylaminoethyl)-1-[4-[4-[(3S)-3-methylmorpholin-4-yl]-6-(methylsulfonylmethyl)pyrimidine-2-yl]phenyl]urea,
3-(2-hydroxyethyl)-1-[4-[4-[(3S)-3-meth is morpholin-4-yl]-6-(methylsulfonylmethyl)pyrimidine-2-yl]phenyl]urea,
3-hydroxy-N-[4-[4-[(3S)-3-methylmorpholin-4-yl]-6-(methylsulfonylmethyl)pyrimidine-2-yl]phenyl]piperidine-1-carboxamide,
1-(2-dimethylaminoethyl)-1-methyl-3-[4-[4-[(3S)-3-methylmorpholin-4-yl]-6-(methylsulfonylmethyl)pyrimidine-2-yl]phenyl]urea,
1-[4-[4-[(3S)-3-methylmorpholin-4-yl]-6-(methylsulfonylmethyl)pyrimidine-2-yl]phenyl]-3-(2-morpholine-4-retil)urea,
3-(1H-imidazol-2-ylmethyl)-1-[4-[4-[(3S)-3-methylmorpholin-4-yl]-6-(methylsulfonylmethyl)pyrimidine-2-yl]phenyl]urea,
1-cyclopropyl-1-methyl-3-[4-[4-[(3S)-3-methylmorpholin-4-yl]-6-(methylsulfonylmethyl)pyrimidine-2-yl]phenyl]urea,
(3S)-3-methyl-N-[4-[4-[(3S)-3-methylmorpholin-4-yl]-6-(methylsulfonylmethyl)pyrimidine-2-yl]phenyl]morpholine-4-carboxamide,
3-cyclopropyl-1-[4-[4-[(3S)-3-methylmorpholin-4-carbonyl]-6-[(3S)-3-methylmorpholin-4-yl]pyrimidine-2-yl]phenyl]urea,
N-cyclopropyl-2-[4-(cyclopropanemethylamine)phenyl]-6-[(3S)-3-methylmorpholin-4-yl]pyrimidine-4-carboxamide,
3-cyclopropyl-1-[4-[4-[(3S)-3-methylmorpholin-4-yl]-6-(4-methylpiperazin-1-carbonyl)pyrimidine-2-yl]phenyl]urea,
3-cyclopropyl-1-[4-[4-(2-hydroxypropan-2-yl)-6-[(3S)-3-methylmorpholin-4-yl]pyrimidine-2-yl]phenyl]urea,
1-[4-[4-(2-hydroxypropan-2-yl)-6-[(3S)-3-methylmorpholin-4-yl]pyrimidine-2-yl]phenyl]-3-[(1-methylpyrazole-4-yl)methyl]urea,
1-[4-[4-(hydroxymethyl)-6-[(3S)-3-methylmorpholin-4-yl]pyrimidine-2-yl]phenyl]-3-(1,2-oxazol-3-yl)urea,
N-[2-[[6-[(3S)-3-methylmorpholin-4-yl]-2-[4-(1,2-oxazol-3-ylcarbonyl the Mino)phenyl]pyrimidine-4-yl]methylsulphonyl]ethyl]acetamide", she
1-[4-[4-(2-hydroxyethylaminomethyl)-6-[(3S)-3-methylmorpholin-4-yl]pyrimidine-2-yl]phenyl]-3-(1,2-oxazol-3-yl)urea,
1-[4-[4-(2-hydroxypropan-2-yl)-6-[(3S)-3-methylmorpholin-4-yl]pyrimidine-2-yl]phenyl]-3-(1,2-oxazol-3-yl)urea,
3-cyclopropyl-1-[4-[4-(hydroxymethyl)-6-[(3S)-3-methylmorpholin-4-yl]pyrimidine-2-yl]phenyl]urea,
3-cyclopropyl-1-[4-[4-[(3S)-3-methylmorpholin-4-yl]-6-(pyridine-4-ylsulphonyl)pyrimidine-2-yl]phenyl]urea,
2-[[2-[4-(cyclopropanemethylamine)phenyl]-6-[(3S)-3-methylmorpholin-4-yl]pyrimidine-4-yl]methylsulphonyl]-N-methyl-acetamide", she
3-cyclopropyl-1-[4-[4-[(4-forfinal)sulfanilyl]-6-[(3S)-3-methylmorpholin-4-yl]pyrimidine-2-yl]phenyl]urea,
N-[4-[[2-[4-(cyclopropanemethylamine)phenyl]-6-[(3S)-3-methylmorpholin-4-yl]pyrimidine-4-yl]methylsulphonyl]phenyl]acetamide", she
3-cyclopropyl-1-[4-[4-(2-hydroxyethylaminomethyl)-6-[(3S)-3-methylmorpholin-4-yl]pyrimidine-2-yl]phenyl]urea,
3-cyclopropyl-1-[4-[4-[(3S)-3-methylmorpholin-4-yl]-6-(1,3-thiazol-2-ylsulphonyl)pyrimidine-2-yl]phenyl]urea,
3-cyclopropyl-1-[4-[4-[(3S)-3-methylmorpholin-4-yl]-6-[[2-(trifluoromethyl)phenyl]sulfanilyl]pyrimidine-2-yl]phenyl]urea,
3-cyclopropyl-1-[4-[4-[(3S)-3-methylmorpholin-4-yl]-6-[(5-methyl-1,3,4-thiadiazole-2-yl)sulfanilyl]pyrimidine-2-yl]phenyl]urea,
2-[[2-[4-(cyclopropanemethylamine)phenyl]-6-[(3S)-3-methylmorpholin-4-yl]pyrimidine-4-yl]methylsulphonyl]ndimethylacetamide,
3-cyclopropyl-1-[4-[4-[(3S)-3-metil Holin-4-yl]-6-[(4-methyl-1,3-thiazol-2-yl)sulfanilyl]pyrimidine-2-yl]phenyl]urea,
N-[2-[[2-[4-(cyclopropanemethylamine)phenyl]-6-[(3S)-3-methylmorpholin-4-yl]pyrimidine-4-yl]methylsulphonyl]ethyl]acetamide", she
1-[4-[4-(1-adamantylamine)-6-[(3S)-3-methylmorpholin-4-yl]pyrimidine-2-yl]phenyl]-3-cyclopropylamino,
3-cyclopropyl-1-[4-[4-(3-hydroxypropylmethacrylate)-6-[(3S)-3-methylmorpholin-4-yl]pyrimidine-2-yl]phenyl]urea,
3-cyclopropyl-1-[4-[4-(3-hydroxypropylmethacrylate)-6-[(3S)-3-methylmorpholin-4-yl]pyrimidine-2-yl]phenyl]urea,
1-(2-hydroxyethyl)-1-methyl-3-[4-[4-(methylsulfonylmethyl)-6-morpholine-4-yl-pyrimidine-2-yl]phenyl]urea,
N-[4-[4-(methylsulfonylmethyl)-6-morpholine-4-yl-pyrimidine-2-yl]phenyl]piperidine-1-carboxamide,
1-(2-methylpropyl)-3-[4-[4-(methylsulfonylmethyl)-6-morpholine-4-yl-pyrimidine-2-yl]phenyl]urea,
1-(3-methoxypropyl)-3-[4-[4-(methylsulfonylmethyl)-6-morpholine-4-yl-pyrimidine-2-yl]phenyl]urea,
1-(4-dimethylaminomethyl)-3-[4-[4-(methylsulfonylmethyl)-6-morpholine-4-yl-pyrimidine-2-yl]phenyl]urea,
1-[4-[4-(methylsulfonylmethyl)-6-morpholine-4-yl-pyrimidine-2-yl]phenyl]-3-[2-(2-Oxymetazoline-1-yl)ethyl]urea,
N-[4-[4-(methylsulfonylmethyl)-6-morpholine-4-yl-pyrimidine-2-yl]phenyl]pyrrolidin-1-carboxamid,
N-[4-[4-(methylsulfonylmethyl)-6-morpholine-4-yl-pyrimidine-2-yl]phenyl]morpholine-4-carboxamide,
4-hydroxy-N-[4-[4-(methylsulfonylmethyl)-6-morpholine-4-yl-pyrimidine-2-yl]phenyl]piperidine-1-carboxamide,
1-(1-methoxypropan-2-yl)-3-[4-[4-(methyls lformer)-6-morpholine-4-yl-pyrimidine-2-yl]phenyl]urea,
1-(2-dimethylaminoethyl)-3-[4-[4-(methylsulfonylmethyl)-6-morpholine-4-yl-pyrimidine-2-yl]phenyl]urea,
3-(2-hydroxyethyl)-1-[4-[4-(methylsulfonylmethyl)-6-morpholine-4-yl-pyrimidine-2-yl]phenyl]urea,
1-ethyl-1-methyl-3-[4-[4-(methylsulfonylmethyl)-6-morpholine-4-yl-pyrimidine-2-yl]phenyl]urea,
3-hydroxy-N-[4-[4-(methylsulfonylmethyl)-6-morpholine-4-yl-pyrimidine-2-yl]phenyl]piperidine-1-carboxamide,
3-methylsulphonyl-N-[4-[4-(methylsulfonylmethyl)-6-morpholine-4-yl-pyrimidine-2-yl]phenyl]pyrrolidine-1-carboxamide,
1-[4-[4-(methylsulfonylmethyl)-6-morpholine-4-yl-pyrimidine-2-yl]phenyl]-3-(2-morpholine-4-retil)urea,
1-(2,2-dimethylpropyl)-3-[4-[4-(methylsulfonylmethyl)-6-morpholine-4-yl-pyrimidine-2-yl]phenyl]urea,
3-(3-hydroxypropyl)-1-[4-[4-(methylsulfonylmethyl)-6-morpholine-4-Yeremey-2-yl]phenyl]urea,
1-benzyl-1-methyl-3-[4-[4-(methylsulfonylmethyl)-6-morpholine-4-Yeremey-2-yl]phenyl]urea,
1-(2-ethoxyethyl)-3-[4-[4-(methylsulfonylmethyl)-6-morpholine-4-Yeremey-2-yl]phenyl]urea,
1-(1-hydroxypropan-2-yl)-3-[4-[4-(methylsulfonylmethyl)-6-morpholine-4-Yeremey-2-yl]phenyl]urea,
1-[4-[4-(methylsulfonylmethyl)-6-morpholine-4-yl-pyrimidine-2-yl]phenyl]-3-(oxan-4-yl)urea,
N-[4-[4-(methylsulfonylmethyl)-6-morpholine-4-yl-pyrimidine-2-yl]phenyl]-3-oxo-piperazine-1-carboxamide,
1-[2-(4-methylpiperazin-1-yl)ethyl]-3-[4-[4-(methylsulfonylmethyl)-6-morpholine-4-Yeremey-2-yl]phenyl]urea is,
1-methyl-1-(2-methylsulfonylamino)-3-[4-[4-(methylsulfonylmethyl)-6-morpholine-4-Yeremey-2-yl]phenyl]urea,
N'-methyl-N-[4-[4-(methylsulfonylmethyl)-6-morpholine-4-Yeremey-2-yl]phenyl]piperidine-1,4-dicarboxamide,
N,N-dimethyl-2-[[4-[4-(methylsulfonylmethyl)-6-morpholine-4-Yeremey-2-yl]phenyl]carbamoylating]ndimethylacetamide,
4-methyl-N-[4-[4-[(3S)-3-methylmorpholin-4-yl]-6-(methylsulfonylmethyl)pyrimidine-2-yl]phenyl]-3-oxopiperidin-1-carboxamid,
4-dimethylamino-N-[4-[4-[(3S)-3-methylmorpholin-4-yl]-6-(methylsulfonylmethyl)pyrimidine-2-yl]phenyl]piperidine-1-carboxamide,
3-methyl-1-[5-[4-[(3S)-3-methylmorpholin-4-yl]-6-(methylsulfonylmethyl)pyrimidine-2-yl]-1,3-thiazol-2-yl]urea,
1-[5-[4-[(3S)-3-methylmorpholin-4-yl]-6-(methylsulfonylmethyl)pyrimidine-2-yl]-1,3-thiazol-2-yl]-3-propan-2-rocephine,
1-ethyl-3-[5-[4-[(3S)-3-methylmorpholin-4-yl]-6-(methylsulfonylmethyl)pyrimidine-2-yl]-1,3-thiazol-2-yl]urea,
1-[5-[4-[(3S)-3-methylmorpholin-4-yl]-6-(methylsulfonylmethyl)pyrimidine-2-yl]-1,3-thiazol-2-yl]-3-phenyl-urea,
3-(4-forfinal)-1-[5-[4-[(3S)-3-methylmorpholin-4-yl]-6-(methylsulfonylmethyl)pyrimidine-2-yl]-1,3-thiazol-2-yl]urea,
1-cyclopropyl-1-methyl-3-[5-[4-[(3S)-3-methylmorpholin-4-yl]-6-(methylsulfonylmethyl)pyrimidine-2-yl]-1,3-thiazol-2-yl]urea,
3-(4-methoxyphenyl)-1-[5-[4-[(3S)-3-methylmorpholin-4-yl]-6-(methylsulfonylmethyl)pyrimidine-2-yl]-1,3-thiazol-2-yl]urea,
3-(2-dimethylaminoethyl)-1-[5-[4-[(3S)-3-methylmorpholin-4-yl]-6-(matilal phenylethyl)pyrimidine-2-yl]-1,3-thiazol-2-yl]urea,
1-[5-[4-[(3S)-3-methylmorpholin-4-yl]-6-(methylsulfonylmethyl)pyrimidine-2-yl]-1,3-thiazol-2-yl]-3-(1-methylpyrazole-4-yl)urea,
3-cyclopropyl-1-[5-[4-[(3S)-3-methylmorpholin-4-yl]-6-(methylsulfonylmethyl)pyrimidine-2-yl]-1,3-thiazol-2-yl]urea,
3-methyl-1-[5-[4-[(3S)-3-methylmorpholin-4-yl]-6-(2-methylsulfonylamino-2-yl)pyrimidine-2-yl]-1,3-thiazol-2-yl]urea,
3-cyclopropyl-1-[5-[4-[(3S)-3-methylmorpholin-4-yl]-6-(2-methylsulfonylamino-2-yl)pyrimidine-2-yl]-1,3-thiazol-2-yl]urea,
1-[5-[4-[(3S)-3-methylmorpholin-4-yl]-6-(2-methylsulfonylamino-2-yl)pyrimidine-2-yl]-1,3-thiazol-2-yl]-3-(1-methylpyrazole-4-yl)urea,
1-[5-[4-[(3S)-3-methylmorpholin-4-yl]-6-(2-methylsulfonylamino-2-yl)pyrimidine-2-yl]-1,3-thiazol-2-yl]-3-[(1-methylpyrazole-4-yl)methyl]urea,
1-ethyl-3-[5-[4-[(3S)-3-methylmorpholin-4-yl]-6-(2-methylsulfonylamino-2-yl)pyrimidine-2-yl]-1,3-thiazol-2-yl]urea,
3-cyclobutyl-[4-[4-[(3S)-3-methylmorpholin-4-yl]-6-(pyridine-4-ylsulphonyl)pyrimidine-2-yl]phenyl]urea,
3-ethyl-1-[4-[4-[(3S)-3-methylmorpholin-4-yl]-6-(pyridine-4-ylsulphonyl)pyrimidine-2-yl]phenyl]urea,
3-(2-dimethylaminoethyl)-1-[4-[4-[(3S)-3-methylmorpholin-4-yl]-6-(pyridine-4-ylsulphonyl)pyrimidine-2-yl]phenyl]urea,
3-cyclopropyl-1-[4-[4-[(cyclopropylamino)methyl]-6-[(3S)-3-methylmorpholin-4-yl]pyrimidine-2-yl]phenyl]urea,
3-cyclopropyl-1-[4-[4-[(2-hydroxyethylamino)methyl]-6-[(3S)-3-methylmorpholin-4-yl]pyrimidine-2-yl]phenyl]urea,
3-cyclopropyl-1-[4[4-[(3S)-3-methylmorpholin-4-yl]-6-[(4-methylpiperazin-1-yl)methyl]pyrimidine-2-yl]phenyl]urea,
3-cyclopropyl-1-[4-[4-[(2-methoxyethylamine)methyl]-6-[(3S)-3-methylmorpholin-4-yl]pyrimidine-2-yl]phenyl]urea,
3-cyclopropyl-1-[4-[4-(dimethylaminomethyl)-6-[(3S)-3-methylmorpholin-4-yl]pyrimidine-2-yl]phenyl]urea,
3-cyclopropyl-1-[4-[4-[(3-dimethylaminopropylamine)methyl]-6-[(3S)-3-methylmorpholin-4-yl]pyrimidine-2-yl]phenyl]urea,
3-cyclopropyl-1-[4-[4-[(3S)-3-methylmorpholin-4-yl]-6-(morpholine-4-ylmethyl)pyrimidine-2-yl]phenyl]urea,
3-cyclopropyl-1-[4-[4-[(2-diethylaminoethylamine)methyl]-6-[(3S)-3-methylmorpholin-4-yl]pyrimidine-2-yl]phenyl]urea,
3-cyclopropyl-1-[4-[4-[(4-methyl-1,4-diazepan-1-yl)methyl]-6-[(3S)-3-methylmorpholin-4-yl]pyrimidine-2-yl]phenyl]urea,
3-cyclopropyl-1-[4-[4-[[(1-hydroxy-2-methyl-propane-2-yl)amino]methyl]-6-[(3S)-3-methylmorpholin-4-yl]pyrimidine-2-yl]phenyl]urea,
3-cyclopropyl-1-[4-[4-[(3S)-3-methylmorpholin-4-yl]-6-[(3-oxopiperidin-1-yl)methyl]pyrimidine-2-yl]phenyl]urea,
3-cyclopropyl-1-[4-[4-[(3-hydroxyazetidine-1-yl)methyl]-6-[(3S)-3-methylmorpholin-4-yl]pyrimidine-2-yl]phenyl]urea,
3-cyclopropyl-1-[4-[4-[(3S)-3-methylmorpholin-4-yl]-6-[[(3S)-3-methylmorpholin-4-yl]methyl]pyrimidine-2-yl]phenyl]urea,
3-cyclopropyl-1-[4-[4-[(1,1-dioxo-1,4-diazinon-4-yl)methyl]-6-[(3S)-3-methylmorpholin-4-yl]pyrimidine-2-yl]phenyl]urea,
1-[4-[4-(hydroxymethyl)-6-[(3S)-3-methylmorpholin-4-yl]pyrimidine-2-yl]phenyl]-3-[(1-methylpyrazole-4-yl)methyl]urea,
1-[4-[4-[(3S)-3-methylmorpholin-4-yl]-6-[(4-methylpiperazin-1-yl)methyl]eremein-2-yl]phenyl]-3-[(1-methylpyrazole-4-yl)methyl]urea,
1-[4-[4-[(cyclopropylamino)methyl]-6-[(3S)-3-methylmorpholin-4-yl]pyrimidine-2-yl]phenyl]-3-[(1-methylpyrazole-4-yl)methyl]urea,
1-[4-[4-[(cyclopropylamino)methyl]-6-[(3S)-3-methylmorpholin-4-yl]pyrimidine-2-yl]phenyl]-3-[(1-methylpyrazole-4-yl)methyl]urea,
N-[2-[[6-[(3S)-3-methylmorpholin-4-yl]-2-[4-[(1-methylpyrazole-4-yl)methylcarbamoyl]phenyl]pyrimidine-4-yl]methylsulphonyl]ethyl]acetamide", she
2-[[6-[(3S)-3-methylmorpholin-4-yl]-2-[4-[(1-methylpyrazole-4-yl)methylcarbamoyl]phenyl]pyrimidine-4-yl]methylsulphonyl]ndimethylacetamide,
1-[4-[4-(2-hydroxyethylaminomethyl)-6-[(3S)-3-methylmorpholin-4-yl]pyrimidine-2-yl]phenyl]-3-[(1-methylpyrazole-4-yl)methyl]urea,
1-[4-[4-[(3S)-3-methylmorpholin-4-yl]-6-(pyridine-4-ylsulphonyl)pyrimidine-2-yl]phenyl]-3-[(1-methylpyrazole-4-yl)methyl]urea,
N-[2-[[6-[(3S)-3-methylmorpholin-4-yl]-2-[4-[(1-methylpyrazole-4-yl)methylcarbamoyl]phenyl]pyrimidine-4-yl]methylsulfanyl]ethyl]acetamide", she
2-[[6-[(3S)-3-methylmorpholin-4-yl]-2-[4-[(1-methylpyrazole-4-yl)methylcarbamoyl]phenyl]pyrimidine-4-yl]methylsulfanyl]ndimethylacetamide,
1-[4-[4-(2-hydroxyethylaminomethyl)-6-[(3S)-3-methylmorpholin-4-yl]pyrimidine-2-yl]phenyl]-3-[(1-methylpyrazole-4-yl)methyl]urea,
1-[4-[4-[(3S)-3-methylmorpholin-4-yl]-6-(pyridine-4-ylsulphonyl)pyrimidine-2-yl]phenyl]-3-[(1-methylpyrazole-4-yl)methyl]urea,
3-cyclopropyl-1-[4-[4-(methoxymethyl)-6-[(3S)-3-methylmorpholin-4-yl]pyrimidine-2-yl]phenyl]urea,
3-cyclopropyl-1-[4-[4-(cyclo is propylsulfonyl)-6-[(3S)-3-methylmorpholin-4-yl]pyrimidine-2-yl]phenyl]urea,
3-cyclopropyl-1-[4-[4-(2-cyclopropanesulfonyl-2-yl)-6-[(3S)-3-methylmorpholin-4-yl]pyrimidine-2-yl]phenyl]urea,
1-[4-[4-(2-cyclopropanesulfonyl-2-yl)-6-[(3S)-3-methylmorpholin-4-yl]pyrimidine-2-yl]phenyl]-3-metalmachine,
1-[4-[4-(2-cyclopropanesulfonyl-2-yl)-6-[(3S)-3-methylmorpholin-4-yl]pyrimidine-2-yl]phenyl]-3-(1-hydroxy-2-methyl-propane-2-yl)urea,
1-[4-[4-(2-cyclopropanesulfonyl-2-yl)-6-[(3S)-3-methylmorpholin-4-yl]pyrimidine-2-yl]phenyl]-3-(2-dimethylaminoethyl)urea,
1-[4-[4-(2-cyclopropanesulfonyl-2-yl)-6-[(3S)-3-methylmorpholin-4-yl]pyrimidine-2-yl]phenyl]-3-(1-methylpyrazole-4-yl)urea,
1-[4-[4-(cyclopropanesulfonyl)-6-[(3S)-3-methylmorpholin-4-yl]pyrimidine-2-yl]phenyl]-3-methyl-urea,
1-[4-[4-(cyclopropanesulfonyl)-6-[(3S)-3-methylmorpholin-4-yl]pyrimidine-2-yl]phenyl]-3-(1-hydroxy-2-methyl-propane-2-yl)urea,
1-[4-[4-(cyclopropanesulfonyl)-6-[(3S)-3-methylmorpholin-4-yl]pyrimidine-2-yl]phenyl]-3-(2-dimethylaminoethyl)urea,
1-[4-[4-(cyclopropanesulfonyl)-6-[(3S)-3-methylmorpholin-4-yl]pyrimidine-2-yl]phenyl]-3-(1-methylpyrazole-4-yl)urea,
3-cyclobutyl-1-[4-[4-(2-cyclopropanesulfonyl-2-yl)-6-[(3S)-3-methylmorpholin-4-yl]pyrimidine-2-yl]phenyl]urea,
1-[4-[4-(2-cyclopropanesulfonyl-2-yl)-6-[(3S)-3-methylmorpholin-4-yl]pyrimidine-2-yl]phenyl]-3-(2-hydroxyethyl)urea,
1-[4-[4-(cyclopropanesulfonyl)-6-[(3S)-3-methylmorpholin-4-yl]pyrimidine-2-yl]Fe is Il]-3-ethyl-urea,
1-[4-[4-(2-cyclopropanesulfonyl-2-yl)-6-[(3S)-3-methylmorpholin-
4-yl]pyrimidine-2-yl]phenyl]-3-ethyl-urea,
3-cyclobutyl-[4-[4-(cyclopropanesulfonyl)-6-[(3S)-3-methylmorpholin-4-yl]pyrimidine-2-yl]phenyl]urea,
3-methyl-1-[4-[4-[(3S)-3-methylmorpholin-4-yl]-6-(2-pyridin-4-ylsulphonyl-2-yl)pyrimidine-2-yl]phenyl]urea,
3-ethyl-1-[4-[4-[(3S)-3-methylmorpholin-4-yl]-6-(2-pyridin-4-ylsulphonyl-2-yl)pyrimidine-2-yl]phenyl]urea,
3-cyclopropyl-1-[4-[4-[(3S)-3-methylmorpholin-4-yl]-6-(2-pyridin-4-ylsulphonyl-2-yl)pyrimidine-2-yl]phenyl]urea,
3-cyclobutyl-1-[4-[4-[(3S)-3-methylmorpholin-4-yl]-6-(2-pyridin-4-ylsulphonyl-2-yl)pyrimidine-2-yl]phenyl]urea,
3-(2-hydroxyethyl)-1-[4-[4-[(3S)-3-methylmorpholin-4-yl]-6-(2-pyridin-4-ylsulphonyl-2-yl)pyrimidine-2-yl]phenyl]urea,
3-(2-dimethylaminoethyl)-1-[4-[4-[(3S)-3-methylmorpholin-4-yl]-6-(2-pyridin-4-ylsulphonyl-2-yl)pyrimidine-2-yl]phenyl]urea,
3-ethyl-1-[4-[4-(2-hydroxyethylaminomethyl)-6-[(3S)-3-methylmorpholin-4-yl]pyrimidine-2-yl]phenyl]urea,
3-cyclobutyl-1-[4-[4-(2-hydroxyethylaminomethyl)-6-[(3S)-3-methylmorpholin-4-yl]pyrimidine-2-yl]phenyl]urea,
3-(2-dimethylaminoethyl)-1-[4-[4-(2-hydroxyethylaminomethyl)-6-[(3S)-3-methylmorpholin-4-yl]pyrimidine-2-yl]phenyl]urea,
3-cyclobutyl-1-[4-[4-[(3S)-3-methylmorpholin-4-yl]-6-(propane-2-ylsulphonyl)pyrimidine-2-yl]phenyl]urea,
3-[4-[4-[(3S)-3-methylmorpholin-4-yl]-6-(about the an-2-ylsulphonyl)pyrimidine-2-yl]phenyl]-1-propylbetaine,
1-[4-[4-[(3S)-3-methylmorpholin-4-yl]-6-(propane-2-ylsulphonyl)pyrimidine-2-yl]phenyl]-3-(2-methylpropyl)urea,
3-(3-hydroxypropyl)-1-[4-[4-[(3S)-3-methylmorpholin-4-yl]-6-(propane-2-ylsulphonyl)pyrimidine-2-yl]phenyl]urea,
1-[4-[4-[(3S)-3-methylmorpholin-4-yl]-6-(propane-2-ylsulphonyl)pyrimidine-2-yl]phenyl]-3-[4-(trifluoromethyl)phenyl]urea,
1-[4-[4-[(3S)-3-methylmorpholin-4-yl]-6-(propane-2-ylsulphonyl)pyrimidine-2-yl]phenyl]-3-pyridin-2-yl-urea,
1-[4-[4-[(3S)-3-methylmorpholin-4-yl]-6-(propane-2-ylsulphonyl)pyrimidine-2-yl]phenyl]-3-propan-2-yl-urea,
3-(1-hydroxy-2-methyl-propane-2-yl)-1-[4-[4-[(3S)-3-methylmorpholin-4-yl]-6-(propane-2-ylsulphonyl)pyrimidine-2-yl]phenyl]urea,
1-[4-[4-[(3S)-3-methylmorpholin-4-yl]-6-(propane-2-ylsulphonyl)pyrimidine-2-yl]phenyl]-3-(1-methylpyrazole-4-yl)urea,
3-methyl-1-[4-[4-[(3S)-3-methylmorpholin-4-yl]-6-(2-propan-2-ylsulphonyl-2-yl)pyrimidine-2-yl]phenyl]urea,
1-ethyl-3-[4-[4-[(3S)-3-methylmorpholin-4-yl]-6-(2-propan-2-ylsulphonyl-2-yl)pyrimidine-2-yl]phenyl]urea,
1-[4-[4-[(3S)-3-methylmorpholin-4-yl]-6-(2-propan-2-ylsulphonyl-2-yl)pyrimidine-2-yl]phenyl]-3-propan-2-yl-urea,
3-cyclopropyl-1-[4-[4-[(3S)-3-methylmorpholin-4-yl]-6-(2-propan-2-ylsulphonyl-2-yl)pyrimidine-2-yl]phenyl]urea,
3-cyclobutyl-1-[4-[4-[(3S)-3-methylmorpholin-4-yl]-6-(2-propan-2-ylsulphonyl-2-yl)pyrimidine-2-yl]phenyl]urea,
3-(2-hydroxyethyl)-1-[4-[4-[(3S)-3-METI the morpholine-4-yl]-6-(2-propan-2-ylsulphonyl-2-yl)pyrimidine-2-yl]phenyl]urea,
3-(1-hydroxy-2-methylpropan-2-yl)-1-[4-[4-[(3S)-3-methylmorpholin-4-yl]-6-(2-propan-2-ylsulphonyl-2-yl)pyrimidine-2-yl]phenyl]urea,
3-(2-dimethylaminoethyl)-1-[4-[4-[(3S)-3-methylmorpholin-4-yl]-6-(2-propan-2-ylsulphonyl-2-yl)pyrimidine-2-yl]phenyl]urea,
3-[4-[4-[(3S)-3-methylmorpholin-4-yl]-6-(2-propan-2-ylsulphonyl-2-yl)pyrimidine-2-yl]phenyl]-1-propylbetaine,
1-[4-[4-[(3S)-3-methylmorpholin-4-yl]-6-(2-propan-2-ylsulphonyl-2-yl)pyrimidine-2-yl]phenyl]-3-(2-methylpropyl)urea,
3-(3-hydroxypropyl)-1-[4-[4-[(3S)-3-methylmorpholin-4-yl]-6-(2-propan-2-ylsulphonyl-2-yl)pyrimidine-2-yl]phenyl]urea,
1-[4-[4-[(3S)-3-methylmorpholin-4-yl]-6-(2-propan-2-ylsulphonyl-2-yl)pyrimidine-2-yl]phenyl]-3-[4-(trifluoromethyl)phenyl]urea,
1-[4-[4-[(3S)-3-methylmorpholin-4-yl]-6-(2-propan-2-ylsulphonyl-2-yl)pyrimidine-2-yl]phenyl]-3-pyridin-2-yl-urea,
1-[4-[4-[(3S)-3-methylmorpholin-4-yl]-6-(2-propan-2-ylsulphonyl-2-yl)pyrimidine-2-yl]phenyl]-3-(1-methylpyrazole-4-yl)urea,
3-cyclobutyl-[4-[4-[(4-forfinal)sulfanilyl]-6-[(3S)-3-methylmorpholin-4-yl]pyrimidine-2-yl]phenyl]urea,
1-ethyl-3-[4-[4-[(4-forfinal)sulfanilyl]-6-[(3S)-3-methylmorpholin-4-yl]pyrimidine-2-yl]phenyl]urea,
1-[4-[4-[(4-forfinal)sulfanilyl]-6-[(3S)-3-methylmorpholin-4-yl]pyrimidine-2-yl]phenyl]-3-propan-2-rocephine,
1-[4-[4-[(4-forfinal)sulfanilyl]-6-[(3S)-3-methylmorpholin-4-yl]pyrimidine-2-yl]phenyl]-3-(2-hydroxyethyl)mochaui is a,
1-[4-[4-[(4-forfinal)sulfanilyl]-6-[(3S)-3-methylmorpholin-4-yl]pyrimidine-2-yl]phenyl]-3-(1-hydroxy-2-methylpropan-2-yl)urea,
3-(2-dimethylaminoethyl)-1-[4-[4-[(4-forfinal)sulfanilyl]-6-[(3S)-3-methylmorpholin-4-yl]pyrimidine-2-yl]phenyl]urea,
3-[4-[4-[(4-forfinal)sulfanilyl]-6-[(3S)-3-methylmorpholin-4-yl]pyrimidine-2-yl]phenyl]-1-propylbetaine,
1-[4-[4-[(4-forfinal)sulfanilyl]-6-[(3S)-3-methylmorpholin-4-yl]pyrimidine-2-yl]phenyl]-3-(2-methylpropyl)urea,
1-[4-[4-[(4-forfinal)sulfanilyl]-6-[(3S)-3-methylmorpholin-4-yl]pyrimidine-2-yl]phenyl]-3-(3-hydroxypropyl)urea,
1-[4-[4-[(4-forfinal)sulfanilyl]-6-[(3S)-3-methylmorpholin-4-yl]pyrimidine-2-yl]phenyl]-3-[4-(trifluoromethyl)phenyl]urea,
1-[4-[4-[(4-forfinal)sulfanilyl]-6-[(3S)-3-methylmorpholin-4-yl]pyrimidine-2-yl]phenyl]-3-pyridine-2-rocephine,
1-[4-[4-[2-(4-forfinal)sulfonylurea-2-yl]-6-[(3S)-3-methylmorpholin-4-yl]pyrimidine-2-yl]phenyl]-3-metalmachine,
1-ethyl-3-[4-[4-[2-(4-forfinal)sulfonylurea-2-yl]-6-[(3S)-3-methylmorpholin-4-yl]pyrimidine-2-yl]phenyl]urea,
1-[4-[4-[2-(4-forfinal)sulfonylurea-2-yl]-6-[(3S)-3-methylmorpholin-4-yl]pyrimidine-2-yl]phenyl]-3-propan-2-rocephine,
3-cyclobutyl-[4-[4-[2-(4-forfinal)sulfonylurea-2-yl]-6-[(3S)-3-methylmorpholin-4-yl]pyrimidine-2-yl]phenyl]urea,
3-(2-dimethylaminoethyl)-1-[4-[4-[2-(4-forfinal)sulfonylurea-2-yl]-6-[(3S)-3-methylmorpholin-4-yl]pyrimidine-2-yl]phenyl]urea,
1-[4-[4-[2-(4-f is arvanil)sulfonylurea-2-yl]-6-[(3S)-3-methylmorpholin-4-yl]pyrimidine-2-yl]phenyl]-3-(2-hydroxyethyl)urea,
3-cyclopropyl-1-[4-[4-[2-(4-forfinal)sulfonylurea-2-yl]-6-[(3S)-3-methylmorpholin-4-yl]pyrimidine-2-yl]phenyl]urea,
3-cyclopropyl-1-[4-[4-(2-ethylsulfonyl-2-yl)-6-[(3S)-3-methylmorpholin-4-yl]pyrimidine-2-yl]phenyl]urea,
1-[4-[4-(2-ethylsulfonyl-2-yl)-6-[(3S)-3-methylmorpholin-4-yl]pyrimidine-2-yl]phenyl]-3-metalmachine,
1-ethyl-3-[4-[4-(2-ethylsulfonyl-2-yl)-6-[(3S)-3-methylmorpholin-4-yl]pyrimidine-2-yl]phenyl]urea,
3-(2-dimethylaminoethyl)-1-[4-[4-(2-ethylsulfonyl-2-yl)-6-[(3S)-3-methylmorpholin-4-yl]pyrimidine-2-yl]phenyl]urea,
1-[4-[4-(2-ethylsulfonyl-2-yl)-6-[(3S)-3-methylmorpholin-4-yl]pyrimidine-2-yl]phenyl]-3-(2-hydroxyethyl)urea,
3-cyclobutyl-1-[4-[4-(2-ethylsulfonyl-2-yl)-6-[(3S)-3-methylmorpholin-4-yl]pyrimidine-2-yl]phenyl]urea,
3-cyclobutyl-1-[4-[4-(ethylsulfonyl)-6-[(3S)-3-methylmorpholin-4-yl]pyrimidine-2-yl]phenyl]urea,
1-ethyl-3-[4-[4-(ethylsulfonyl)-6-[(3S)-3-methylmorpholin-4-yl]pyrimidine-2-yl]phenyl]urea,
3-(2-dimethylaminoethyl)-1-[4-[4-(ethylsulfonyl)-6-[(3S)-3-methylmorpholin-4-yl]pyrimidine-2-yl]phenyl]urea,
3-cyclopropyl-1-[4-[4-[(3S)-3-methylmorpholin-4-yl]-6-(morpholine-4-carbonyl)pyrimidine-2-yl]phenyl]urea,
3-cyclopropyl-1-[4-[4-(1,4-diazepan-1-carbonyl)-6-[(3S)-3-methylmorpholin-4-yl]pyrimidine-2-yl]phenyl]urea,
3-cyclopropyl-1-[4-[4-(1,1-dioxo-1,4-diazinon-4-carbonyl)-6-[(3S)-3-methylmorpholin-4-yl]pyrimidine-2-yl]phenyl]urea,
3-qi is sapropel-1-[4-[4-[(2R,6S)-2,6-dimethylmorpholine-4-carbonyl]-6-[(3S)-3-methylmorpholin-4-yl]pyrimidine-2-yl]phenyl]urea,
2-[4-(cyclopropanemethylamine)phenyl]-N,N-dimethyl-6-[(3S)-3-methylmorpholin-4-yl]pyrimidine-4-carboxamide,
2-[4-(cyclopropanemethylamine)phenyl]-N-(2-hydroxyethyl)-N-methyl-6-[(3S)-3-methylmorpholin-4-yl]pyrimidine-4-carboxamide,
2-[4-(cyclopropanemethylamine)phenyl]-N-(2-methoxyethyl)-6-[(3S)-3-methylmorpholin-4-yl]pyrimidine-4-carboxamide,
2-[4-(cyclopropanemethylamine)phenyl]-N-methyl-6-[(3S)-3-methylmorpholin-4-yl]-N-(1-methylpyrrolidine-3-yl)pyrimidine-4-carboxamide,
3-cyclopropyl-1-[4-[4-(4-hydroxypiperidine-1-carbonyl)-6-[(3S)-3-methylmorpholin-4-yl]pyrimidine-2-yl]phenyl]urea,
1-[4-[4-(azepin-1-carbonyl)-6-[(3S)-3-methylmorpholin-4-yl]pyrimidine-2-yl]phenyl]-3-cyclopropylamino,
2-[4-(cyclopropanemethylamine)phenyl]-N-ethyl-6-[(3S)-3-methylmorpholin-4-yl]pyrimidine-4-carboxamide,
2-[4-(cyclopropanemethylamine)phenyl]-N-(2-dimethylaminoethyl)-N-methyl-6-[(3S)-3-methylmorpholin-4-yl]pyrimidine-4-carboxamide,
2-[4-(cyclopropanemethylamine)phenyl]-N-(2-methoxyethyl)-N-methyl-6-[(3S)-3-methylmorpholin-4-yl]pyrimidine-4-carboxamide,
2-[4-(cyclopropanemethylamine)phenyl]-6-[(3S)-3-methylmorpholin-4-yl]-N-(1-methyl-4-piperidyl)pyrimidine-4-carboxamide,
3-cyclopropyl-1-[4-[4-(3-hydroxyazetidine-1-carbonyl)-6-[(3S)-3-methylmorpholin-4-yl]pyrimidine-2-yl]phenyl]urea,
2-[4-(cyclopropanemethylamine)phenyl]-N-[(3-Mei-4-yl)methyl]-6-[(3S)-3-methylmorpholin-4-yl]pyrimidine-4-carboxamide,
2-[4-(cyclopropyl is carbamoylating)phenyl]-N-(dimethylcarbamoyl)-6-[(3S)-3-methylmorpholin-4-yl]pyrimidine-4-carboxamide,
N-cyclopropyl-2-[4-(cyclopropanemethylamine)phenyl]-N-methyl-6-[(3S)-3-methylmorpholin-4-yl]pyrimidine-4-carboxamide,
2-[4-(cyclopropanemethylamine)phenyl]-N-(cyclopropylmethyl)-N-methyl-6-[(3S)-3-methylmorpholin-4-yl]pyrimidine-4-carboxamide,
2-[4-(cyclopropanemethylamine)phenyl]-6-[(3S)-3-methylmorpholin-4-yl]-N-(oxetan-3-yl)pyrimidine-4-carboxamide,
1-[4-[4-(2-cyclopentylmethyl-2-yl)-6-[(3S)-3-methylmorpholin-4-yl]pyrimidine-2-yl]phenyl]-3-cyclopropylamino,
3-cyclobutyl-1-[4-[4-(2-cyclopentylmethyl-2-yl)-6-[(3S)-3-methylmorpholin-4-yl]pyrimidine-2-yl]phenyl]urea,
1-[4-[4-(2-cyclopentylmethyl-2-yl)-6-[(3S)-3-methylmorpholin-4-yl]pyrimidine-2-yl]phenyl]-3-atilmotin,
1-[4-[4-(2-cyclopentylmethyl-2-yl)-6-[(3S)-3-methylmorpholin-4-yl]pyrimidine-2-yl]phenyl]-3-(2-dimethylaminoethyl)urea,
1-[4-[4-(2-cyclopentylmethyl-2-yl)-6-[(3S)-3-methylmorpholin-4-yl]pyrimidine-2-yl]phenyl]-3-(2-hydroxyethyl)urea,
1-[4-[4-(2-cyclopentylmethyl-2-yl)-6-[(3S)-3-methylmorpholin-4-yl]pyrimidine-2-yl]phenyl]-3-metalmachine,
3-cyclobutyl-[4-[4-(cyclopentylmethyl)-6-[(3S)-3-methylmorpholin-4-yl]pyrimidine-2-yl]phenyl]urea,
1-[4-[4-(cyclopentylmethyl)-6-[(3S)-3-methylmorpholin-4-yl]pyrimidine-2-yl]phenyl]-3-atilmotin,
1-[4-[4-(cyclopentylmethyl)-6-[(3S)-3-methylmorpholin-4-yl]pyrimidine-2-yl]phenyl]-3-(2-dimethylaminoethyl)urea,
3-cyclopropyl-1-[4-[-[(3S)-3-methylmorpholin-4-yl]-6-[2-[2-(trifluoromethyl)phenyl]sulfonylurea-2-yl]pyrimidine-2-yl]phenyl]urea,
3-cyclobutyl-1-[4-[4-[(3S)-3-methylmorpholin-4-yl]-6-[2-[2-(trifluoromethyl)phenyl]sulfonylurea-2-yl]pyrimidine-2-yl]phenyl]urea,
3-ethyl-1-[4-[4-[(3S)-3-methylmorpholin-4-yl]-6-[2-[2-(trifluoromethyl)phenyl]sulfonylurea-2-yl]pyrimidine-2-yl]phenyl]urea,
3-(2-dimethylaminoethyl)-1-[4-[4-[(3S)-3-methylmorpholin-4-yl]-6-[2-[2-(trifluoromethyl)phenyl]sulfonylurea-2-yl]pyrimidine-2-yl]phenyl]urea,
3-(2-hydroxyethyl)-1-[4-[4-[(3S)-3-methylmorpholin-4-yl]-6-[2-[2-(trifluoromethyl)phenyl]sulfonylurea-2-yl]pyrimidine-2-yl]phenyl]urea,
3-methyl-1-[4-[4-[(3S)-3-methylmorpholin-4-yl]-6-[2-[2-(trifluoromethyl)phenyl]sulfonylurea-2-yl]pyrimidine-2-yl]phenyl]urea,
3-cyclobutyl-1-[4-[4-[(3S)-3-methylmorpholin-4-yl]-6-[[2-(trifluoromethyl)phenyl]sulfanilyl]pyrimidine-2-yl]phenyl]urea,
3-ethyl-1-[4-[4-[(3S)-3-methylmorpholin-4-yl]-6-[[2-(trifluoromethyl)phenyl]sulfanilyl]pyrimidine-2-yl]phenyl]urea,
3-(2-dimethylaminoethyl)-1-[4-[4-[(3S)-3-methylmorpholin-4-yl]-6-[[2-(trifluoromethyl)phenyl]sulfanilyl]pyrimidine-2-yl]phenyl]urea,
3-ethyl-1-[4-[4-[(3S)-3-methylmorpholin-4-yl]-6-(tert-butylsulfonyl)pyrimidine-2-yl]phenyl]urea,
3-cyclobutyl-1-[4-[4-[(3S)-3-methylmorpholin-4-yl]-6-(tert-butylsulfonyl)pyrimidine-2-yl]phenyl]urea,
3-(2-dimethylaminoethyl)-1-[4-[4-[(3S)-3-methylmorpholin-4-yl]-6-(tert-butylsulfonyl)pyrimidine-2-yl]phenyl]urea,
3-cyclopropyl-1-[4-[4-[(3S)-3-methylmorpholin-4-yl]-6-(2-tert-butylsulfonyl--yl)pyrimidine-2-yl]phenyl]urea,
3-cyclobutyl-1-[4-[4-[(3S)-3-methylmorpholin-4-yl]-6-(2-tert-butylsulfonyl-2-yl)pyrimidine-2-yl]phenyl]urea,
3-ethyl-1-[4-[4-[(3S)-3-methylmorpholin-4-yl]-6-(2-tert-butylsulfonyl-2-yl)pyrimidine-2-yl]phenyl]urea,
3-(2-dimethylaminoethyl)-1-[4-[4-[(3S)-3-methylmorpholin-4-yl]-6-(2-tert-butylsulfonyl-2-yl)pyrimidine-2-yl]phenyl]urea,
3-(2-hydroxyethyl)-1-[4-[4-[(3S)-3-methylmorpholin-4-yl]-6-(2-tert-butylsulfonyl-2-yl)pyrimidine-2-yl]phenyl]urea,
3-methyl-1-[4-[4-[(3S)-3-methylmorpholin-4-yl]-6-(2-tert-butylsulfonyl-2-yl)pyrimidine-2-yl]phenyl]urea,
1-[4-[4-[(3,5-differenl)sulfanilyl]-6-[(3S)-3-methylmorpholin-4-yl]pyrimidine-2-yl]phenyl]-3-atilmotin,
3-cyclobutyl-1-[4-[4-[(3,5-differenl)sulfanilyl]-6-[(3S)-3-methylmorpholin-4-yl]pyrimidine-2-yl]phenyl]urea,
1-[4-[4-[(3,5-differenl)sulfanilyl]-6-[(3S)-3-methylmorpholin-4-yl]pyrimidine-2-yl]phenyl]-3-(2-dimethylaminoethyl)urea,
3-cyclopropyl-1-[4-[4-[2-(3,5-differenl)sulfonylurea-2-yl]-6-[(3S)-3-methylmorpholin-4-yl]pyrimidine-2-yl]phenyl]urea,
3-cyclobutyl-1-[4-[4-[2-(3,5-differenl)sulfonylurea-2-yl]-6-[(3S)-3-methylmorpholin-4-yl]pyrimidine-2-yl]phenyl]urea,
3-[4-[4-[2-(3,5-differenl)sulfonylurea-2-yl]-6-[(3S)-3-methylmorpholin-4-yl]pyrimidine-2-yl]phenyl]-1-atilmotin,
1-[4-[4-[2-(3,5-differenl)sulfonylurea-2-yl]-6-[(3S)-3-methylmorpholin-4-yl]pyrimidine-2-yl]phenyl]-3-(2-dimethylaminoethyl)urea,
1-[4-4-[2-(3,5-differenl)sulfonylurea-2-yl]-6-[(3S)-3-methylmorpholin-4-yl]pyrimidine-2-yl]phenyl]-3-(2-hydroxyethyl)urea,
1-[4-[4-[2-(3,5-differenl)sulfonylurea-2-yl]-6-[(3S)-3-methylmorpholin-4-yl]pyrimidine-2-yl]phenyl]-3-metalmachine,
1-[4-[4-(2-cyclohexylsulfamate-2-yl)-6-[(3S)-3-methylmorpholin-4-yl]pyrimidine-2-yl]phenyl]-3-cyclopropylamino,
3-cyclobutyl-1-[4-[4-(2-cyclohexylsulfamate-2-yl)-6-[(3S)-3-methylmorpholin-4-yl]pyrimidine-2-yl]phenyl]urea,
3-[4-[4-(2-cyclohexylsulfamate-2-yl)-6-[(3S)-3-methylmorpholin-4-yl]pyrimidine-2-yl]phenyl]-1-atilmotin,
1-[4-[4-(2-cyclohexylsulfamate-2-yl)-6-[(3S)-3-methylmorpholin-4-yl]pyrimidine-2-yl]phenyl]-3-(2-dimethylaminoethyl)urea,
1-[4-[4-(2-cyclohexylsulfamate-2-yl)-6-[(3S)-3-methylmorpholin-4-yl]pyrimidine-2-yl]phenyl]-3-(2-hydroxyethyl)urea,
1-[4-[4-(2-cyclohexylsulfamate-2-yl)-6-[(3S)-3-methylmorpholin-4-yl]pyrimidine-2-yl]phenyl]-3-metalmachine,
3-cyclobutyl-[4-[4-(cyclohexylsulfamate)-6-[(3S)-3-methylmorpholin-4-yl]pyrimidine-2-yl]phenyl]urea,
3-[4-[4-(cyclohexylsulfamate)-6-[(3S)-3-methylmorpholin-4-yl]pyrimidine-2-yl]phenyl]-1-atilmotin,
1-[4-[4-(cyclohexylsulfamate)-6-[(3S)-3-methylmorpholin-4-yl]pyrimidine-2-yl]phenyl]-3-(2-dimethylaminoethyl)urea,
3-cyclopropyl-1-[4-[4-[(3S)-3-methylmorpholin-4-yl]-6-[2-[(4-methyl-1,3-thiazol-2-yl)sulfonyl]propan-2-yl]pyrimidine-2-yl]phenyl]urea,
3-cyclobutyl-1-[4-[4-[(3S)-3-methylmorpholin-4-yl]-6-[2-[(4-methyl-1,3-thiazol-2-yl)sulfonyl]propan-2-yl]pyrimidine-2-yl]phenyl]urea,
3-the Teal-1-[4-[4-[(3S)-3-methylmorpholin-4-yl]-6-[2-[(4-methyl-1,3-thiazol-2-yl)sulfonyl]propan-2-yl]pyrimidine-2-yl]phenyl]urea,
3-(2-dimethylaminoethyl)-1-[4-[4-[(3S)-3-methylmorpholin-4-yl]-6-[2-[(4-methyl-1,3-thiazol-2-yl)sulfonyl]propan-2-yl]pyrimidine-2-yl]phenyl]urea,
3-(2-hydroxyethyl)-1-[4-[4-[(3S)-3-methylmorpholin-4-yl]-6-[2-[(4-methyl-1,3-thiazol-2-yl)sulfonyl]propan-2-yl]pyrimidine-2-yl]phenyl]urea,
3-methyl-1-[4-[4-[(3S)-3-methylmorpholin-4-yl]-6-[2-[(4-methyl-1,3-thiazol-2-yl)sulfonyl]propan-2-yl]pyrimidine-2-yl]phenyl]urea,
3-cyclobutyl-1-[4-[4-[(3S)-3-methylmorpholin-4-yl]-6-[(4-methyl-1,3-thiazol-2-yl)sulfanilyl]pyrimidine-2-yl]phenyl]urea,
3-ethyl-1-[4-[4-[(3S)-3-methylmorpholin-4-yl]-6-[(4-methyl-1,3-thiazol-2-yl)sulfanilyl]pyrimidine-2-yl]phenyl]urea,
3-(2-dimethylaminoethyl)-1-[4-[4-[(3S)-3-methylmorpholin-4-yl]-6-[(4-methyl-1,3-thiazol-2-yl)sulfanilyl]pyrimidine-2-yl]phenyl]urea,
3-ethyl-1-[4-[4-[(3S)-3-methylmorpholin-4-yl]-6-(2-pyridin-2-ylsulphonyl-2-yl)pyrimidine-2-yl]phenyl]urea,
3-ethyl-1-[4-[4-[(3S)-3-methylmorpholin-4-yl]-6-(pyridine-2-ylsulphonyl)pyrimidine-2-yl]phenyl]urea,
1-[4-[4-[2-(4-chlorophenyl)sulfonylurea-2-yl]-6-[(3S)-3-methylmorpholin-4-yl]pyrimidine-2-yl]phenyl]-3-cyclopropyl-urea,
1-[4-[4-[2-(4-chlorophenyl)sulfonylurea-2-yl]-6-[(3S)-3-methylmorpholin-4-yl]pyrimidine-2-yl]phenyl]-3-cyclobutylamine,
1-[4-[4-[2-(4-chlorophenyl)sulfonylurea-2-yl]-6-[(3S)-3-methylmorpholin-4-yl]pyrimidine-2-yl]phenyl]-3-metalmachine,
1-[4-[4-[2-(4-chlorophenyl)sulfonylurea-2-yl]-6-[(3S)-3-methylmorpholin-4-yl]pyrimidine-2-yl]phenyl]-3-etil Cavina,
1-[4-[4-[2-(4-chlorophenyl)sulfonylurea-2-yl]-6-[(3S)-3-methylmorpholin-4-yl]pyrimidine-2-yl]phenyl]-3-(2-dimethylaminoethyl)urea,
(S)-1-(4-(4-((4-chlorophenylsulfonyl)methyl)-6-(3-methylmorpholine)pyrimidine-2-yl)phenyl)-3-cyclobutylamine, and
1-[4-[4-[(4-chlorophenyl)sulfanilyl]-6-[(3S)-3-methylmorpholin-4-yl]pyrimidine-2-yl]phenyl]-3-atilmotin,
or its pharmaceutically acceptable salt.

13. The use of the compounds of formula (I) or its pharmaceutically acceptable salt according to claim 1 for the preparation of drugs having inhibitory activity against mTOR kinase and/or PI3K kinase.

14. Pharmaceutical composition having inhibitory activity against mTOR kinase and/or PI3K kinase, which contains a compound of the formula (I) according to claim 1 or its pharmaceutically acceptable salt, in combination with a pharmaceutically acceptable diluent or carrier.

15. The compound of formula (I) of claim 1 or its pharmaceutically acceptable salt for use as drugs having inhibitory activity against mTOR kinase and/or PI3K kinase.



 

Same patents:

FIELD: chemistry.

SUBSTANCE: invention relates to a compound of general formula where: R1 denotes COORa1, CONRa2Ra2', CONRa4ORa4', where: each of Ra1 and Ra4 denotes a hydrogen atom; each of Ra2 and Ra2' denotes a hydrogen atom; Ra4' denotes a lower alkyl; or R1 denotes a heterocyclic group selected from the following groups, where Y2 denotes a hydrogen atom or a lower alkyl: R2 denotes O, S, SO, SO2; R3 denotes a phenyl which is substituted with 2 substitutes selected from halogen, CF3; X2 denotes CH or N; W denotes the following residue: where: W1 denotes CH or S; W2 denotes CH; W3 denotes C or N; and at least one of W1, W2 and W3 denotes a carbon atom; or pharmaceutically acceptable salt or ester thereof. The invention also relates to a pharmaceutical composition having Avrora A selective inhibitory action, which, along with a pharmaceutically acceptable carrier or diluent, contains at least one compound of formula I a an active ingredient.

EFFECT: aminopyridine or aminopyrazine derivatives which inhibit growth of tumour cells based on Avrora A kinase selective inhibitory action.

11 cl, 3 tbl, 24 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel organic compounds of formula where R1 denotes H; halogen; -C0-C7-alkyl-O-R3; -NR4R5; R2 denotes phenyl, substituted with one or two substitutes selected from a group consisting of C1-7alkyl, halogen-C1-7alkyl, C1-7alkoxy, halogen-C1-7alkoxy, phenoxy, halogen, C1-7alkylpiperazinyl-C1-7alkyl, C3-C8-cyclalkyl, C1-7alkylpiperidinyl-C1-7alkyl and C1-7alkylimidazolyl; R3 denotes H or phenyl-lower alkyl; R4 and R5 are independently selected from a group consisting of H; lower alkyl; lower alkoxy-carbonyl and amino; A, B and X are independently selected from C(R7) or N, provided that not more than one or A, B and X denotes N; R7 denotes H; R8 denotes hydrogen; n equals 0; Y denotes O; Z denotes C; W is absent; K denotes N or C, and either a) if K denotes C, the bond shown by a wavy line () is a double bond, Q is selected from O-N, S-N, O-CH and S-CH, where in each case, the left-hand O or S atom is bonded through a bond shown in formula I to K, the right-hand N or carbon (CH) atom is bonded to C through a bond shown by a dotted line () in formula I, provided that said bond, which is shown by the dotted line, is a double bond with C; and the bond shown by a thick line () is a single bond; or b) if K denotes N, the bond shown by a wavy line () is a single bond; Q denotes N=CH, where the left-hand N atom is bonded through a bond shown in formula I to K, the right-hand carbon (CH) atom is bonded to C through a bond shown by a dotted line () in formula I, provided that said bond, which is shown by a dotted line, is a single bond with C; and the bond shown by thick line () is a double bond; or salt thereof (preferably pharmaceutically acceptable salt). The invention also relates to a pharmaceutical composition, having inhibiting action on protein kinase, containing a compound of formula I or salt thereof in an effective amount and at least one pharmaceutically acceptable carrier material.

EFFECT: heterocyclic carboxamides as kinase inhibitors.

12 cl, 25 ex

FIELD: chemistry.

SUBSTANCE: present invention relates to a compound of formula I or a pharmaceutically acceptable salt thereof, where R1 denotes C1-C8-alkylaminocarbonyl, which is optionally substituted with a 5- or 6-member heterocyclic ring containing 3-4 ring heteroatoms selected from a group consisting of oxygen, nitrogen and sulphur, where the ring can be optionally substituted with C1-C8-alkyl or C1-C8-alkoxy group ; R2 denotes C1-C3-alkyl or a halogen; one of R3 and R4 denotes R6, and the other denotes R7; R5 denotes hydrogen or halogen; R6 denotes hydrogen, hydroxy group amino group, -SO2R8, -SO2NH2, -SO2NR9R10, -COR8, -CONHR8, -NHSO2R8, nitrile, carboxy, -OR8 or C1-C8-halogenalkyl; R7 denotes hydrogen, OR11, halogen, carboxy, -SO2R8, cyanogroup or C1-C8-halogenalkyl, or when R4 denotes R7, then R7 can also denote -NR12 R13 ; R8 R11 independently denote C1-C8-alkyl or C3-C8-cycloalkyl, which can be optionally substituted with hydroxy group, C1-C8-alkoxy group, nitrile, amino group, C1-C8-alkylamino group or di-C1-C8-alkyl)amino group; any R9 denotes C1-C8-alkyl or C3-C8-cycloalkyl, which can optionally be substituted with hydroxy group, C1-C8-alkoxy group, nitrile, amino group, C1-C8-alkylamino group, di(C1-C8-alkyl)amino group or a 5- or 6-member heterocyclic ring containing one or two ring heteroatoms selected from a group consisting of oxygen and nitrogen, where the ring can optionally be substituted with C1-C8-alkyl, and R10 denotes hydrogen or C1-C8-alkyl; or R9 and R10 together with a nitrogen atom with which they are bonded form a 5- or 6-member heterocyclic ring which can contain one or two additional nitrogen heteroatoms, where the ring can be optionally substituted with C1-C8-alkyl; any R12 denotes C1-C8-alkyl or C3-C8-cycloalkyl which can be optionally substituted with di(C1-C8-alkyl)aminogroup, and R13 denotes hydrogen or C1-C8-alkyl; or R12 and R13 together with a nitrogen atom with which they are bonded form a 5- or 6-member heterocyclic ring which contains one or two additional nitrogen heteroatoms, where the ring can optionally be substituted with C1-C8-alkyl.

EFFECT: possibility of using the compounds to produce a pharmaceutical agent for treating diseases mediated by phosphatidylinositol-3 kinase.

6 cl, 3 tbl, 181 ex

FIELD: chemistry.

SUBSTANCE: invention relates to hydroximoyl-tetrazole derivatives of formula (I), , where T is a tetrazole substitute, A is a phenyl or heterocycle, L1 and L2 are different linker groups, and Q is a carbocycle, use thereof as fungicide active agents, particularly in form of fungicide compositions, and methods of controlling phytopathogenic fungi, especially plants, using said compounds or compositions.

EFFECT: more effective use of the compounds.

13 cl, 2 tbl, 2 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel diarylamine-containing compounds of formula (I) or formula (4b), pharmaceutically acceptable salts thereof, which have c-kit inhibiting properties. In formulae (I) and (4b), each R1 independently denotes H, -C(O)OH and -L1-C1-6alkyl, where L1 denotes -O- or -C(O)O-, or any two neighbouring R1 groups can together form a 5-6-member heterocyclic ring containing a nitrogen atom or an oxygen atom as a heteroatom, a 6-member heterocyclic ring with one or two nitrogen atom s as heteroatoms, optionally substituted with a C1-4alkyl, and R5 denotes hydrogen or C1-C6alkyl; values of radicals Ar and Q are given in the claim. The invention also relates to a pharmaceutical composition containing said compounds, and a method of treating diseases whose development is promoted by c-kit receptor activity.

EFFECT: more effective use of the compounds.

17 cl, 3 tbl, 9 ex

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of general formula where R denotes a thiazolyl group of formula R2 and R3 are selected from: hydrogen, C1-C3linear alkyl; R4 is selected from: C1-C3linear or C3cyclic alkyl, phenyl and thiophenyl; Z denotes a group of formula: -(L)n-R1; R1 is selected from: i) C1-C3linear or branched alkyl, optionally substituted with C1-C4alkoxycarbonyl, halogen; ii) substituted phenyl or substituted with one or two substitutes selected from halogen, methoxy- or hydroxy group, C1-C4alkoxycarbonyl; iii) dioxopiperazinyl and 2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl, substituted with C1-C3alkyl; or iv) heteroaryl rings containing 5-10 atoms selected from thiazole, triazole, 1H-imidazole, thiadiazole, oxazole, isoxazole, oxadiazole, benzodioxole, benzo(1,4)dioxepanyl, pyridine, pyrimidine, 1H-indole, 2,3-dihydrobenzo[b][1,4]dioxynil, which can be substituted with oine or two substitutes selected from: a) hydroxy; b) C1-C3alkyl (which can be substituted with one more two substitutes selected from: ) phenyl; ii) C1-C4alkoxycarbonyl; iii) naphthalenyl; iv) 2-methylthiazolyl) ; c) NHC(O)C1-C3alkyl; d) C1-C4alkoxycarbonyl; e) 1 -(tert-butoxycarbonyl)-2-phenylethyl; f) methoxybenzyl; g) phenyl which can be substuted with C1-C4alkoxy, halogen, methoxycarbonyl or >NHC(O)CH3; h) (methoxy-2-oxoethyl)carbamoyl; L denotes a group selected from: i) C(O)NH[C(R5aR5b)]w-; ii) -C(O)[C(R6aR6b)]x-; iii) -C(O)[C(R7aR7b)]yC(O)-; iv) -SO2[C(R8aR8b)]z-; R5a, R5b, R6a, R6b, R7a, R7b, R8a and R8b, each independently denotes: i) hydrogen; ii) C1-C3 linear alkyl which can be substituted with 1 or 2 halogen atoms; iii) phenyl which can be substituted with 1-2 substitutes selected from halogen and lower alkoxy; iv) heteroaryl rings selected from imidazolyl, imidazolyl substituted with methyl, benzo(1,4)oxazinyl, oxadiazolyl substituted with methyl; index n equals 0 or 1; indices w, x, y and z are each independently equal to a number from 1 to 3. The invention also relates to pharmaceutically acceptable salts of compounds of formula (I) and use of compounds of formula (I) to prepare a medicinal agent for treating protein tyrosine phosphatase beta-mediated conditions.

EFFECT: obtaining compounds of formula (I) as human protein tyrosine phosphatase beta (HPTP-β) inhibitors.

15 cl, 17 dwg, 13 tbl, 16 ex

FIELD: chemistry.

SUBSTANCE: invention relates to an isoxazoline-substituted benzamide derivative of formula or salt thereof, where A1 denotes a carbon or nitrogen atom, A2 and A3 independently denote a carbon atom, G denotes a benzene ring, W denotes an oxygen or sulphur atom, X denotes a halogen atom or C1-C6alkyl, arbitrarily substituted with a radical R4, Y denotes a halogen atom, cyano, nitro, C1-C6alkyl, C1-C6alkyl arbitrarily substituted with radical R4, -OR5, -N(R7)R6, phenyl, D-41, when n equals 2, each Y can be identical or different from each other, R1 denotes -C(R1b)=NOR1a, M-5, -C(O)OR1c, -C(O)SR1c, -C(S)OR1c, -C(S)SR1c, -C(O)N(R1e)R1d, -C(S)N(R1e)R1d, -C(R1d)=NN(R1e)R1lf, phenyl, phehnyl substituted with (Z)p1, or D-3, D-8, D-13-D-15, D-21, D-35, D-52-D-55 or D-57-D-59, R2 denotes C1-C6alkyl, -CH2R14a, E-5, C3-C6alkynyl, -C(O)R15, -C(O)OR15, -C(O)C(O)OR15 or -SR15, where, when R1 denotes -C(R1b)=NOR1a, M-5, or -C(R1b)=NN(R1e)R1f, R2 can denote a hydrogen atom, when R1 denotes -C(O)OR1c, -C(O)SR1c, -C(S)OR1c or -C(S)SR1c, R2 can denote hydrogen, when R denotes -C(O)N(R1e)R1d or -C(S)N(R1c)R1d, R2 can denote a hydrogen atom, when R1 denotes phenyl, phenyl substituted with (Z)p1, or D-3, D-8, -D-13-D-15, D-21, D-35, D-52-D-55 or D-57-D-59 R2 can denote C1-C6halogenalkyl, C1-C6alkyl arbitrarily substituted with a radical R14a, C3-C6alkenyl, -C(O)NH2, -C(O)N(R16)R15, or R2 together with R1 can form =C(R2b)R2a, R3 denotes C1-C6alkyl arbitrarily substituted with radical R4, D-1, D-3, D-8, D-13-D-15, D-21, D-35, D-41, D-52-D-55, D-57-D-59 denote aromatic heterocyclic rings, m equals an integer from 2 to 3, n equals an integer from 0 to 2.

EFFECT: isoxazoline-substituted benzamide derivative and salt thereof are used in pest control, against harmful arthropods in agriculture and horticulture or in livestock farming and in the field of hygiene.

12 cl, 18 tbl, 73 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a method of producing 1,7-bis[4(5)-methyl-1,3-thiazol-2-yl]-3,5-dithia-1,7-diazaheptanes of general formula (1), which can be used in organic synthesis to produce macro-heterocyclic rings, as well as sorbents and extraction agents for precious and rare-earth metals. The method is realised by reacting hydrogen sulphide-saturated aqueous formaldehyde solution (37%) with 2-amino-4(5)-methylthiazole with molar ratio of initial reagents 2-amino-4(5)-methylthiazole: formaldehyde: hydrogen sulphide equal to 20:30:20, at temperature -5-5°C and atmospheric pressure for 8-12 hours.

EFFECT: improved method.

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of general formula

, where R is a group selected from: i) hydrogen; ii) phenyl and iii) thiophenyl; Z is a substituted or unsubstituted [1,3,4]thiadiazol-2-yl group, R1 is selected from: i) hydrogen; ii) straight C1-C6alkyl; iii) C6 or C10 aryl; iv) C(O)OR5; and v) 2-methylthiazol-4-yl; R5 denotes a straight or branched C1-C6alkyl; and index x equals 0 or 1. The invention also relates to use of compounds of formula (I) to prepare a medicinal agent having human protein tyrosine phosphatase beta (HPTP-β) inhibiting action and use in treatment.

EFFECT: compounds can be used as human protein tyrosine phosphatase beta inhibitors.

11 cl, 1 dwg, 1 tbl, 1 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a use of N-(2-thiazolyl)amide derivatives of formula

,

where R1 and R2 are independently selected from H, -NO2, halogen, C1-C6 alkyl with a straight chain, where at least one of R1 and R2 is different from H; m equals 0, 1, 2 or 3; X is selected from a group consisting of: indole of formula (A) bound in position 2, indole of formula (B) bound in position 3 and indazole of formula (C) bound in position 3:

, , ,

where R3 is selected from H and C1-C6 alkyl with a straight chain; R4, R5, R6 and R7 are independently selected from H and C1-C6 alkoxy group; R8 is selected from H and C1-C6 alkyl, or any of its pharmaceutically acceptable salts to obtain a medicinal agent for treating or preventing diseases or conditions mediated by GSK-3, especially neurodegenerative diseases such as Alzheimer's disease or insulin-independent sugar diabetes. The invention also relates to a compound of formula (I), a pharmaceutical composition based on said compound and synthesis method thereof.

EFFECT: high efficiency of using said derivatives.

30 cl, 3 tbl, 7 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to novel derivatives of diazepane of formula , where A, X, R3, R4, R5, R6, R8, R9, R10, R11, R12, R13, n and m have values, given in description and formula of invention, as well as their physiologically acceptable salts. Said compounds are antagonists of chemokine receptors CCR-2, CCR-5 and/or CCR-3 receptor and can be used in medicine as medications.

EFFECT: obtaining novel diazepane derivatives.

20 cl, 505 ex, 4 tbl

FIELD: chemistry.

SUBSTANCE: invention relates to novel organic compounds of formula where R1 denotes H; halogen; -C0-C7-alkyl-O-R3; -NR4R5; R2 denotes phenyl, substituted with one or two substitutes selected from a group consisting of C1-7alkyl, halogen-C1-7alkyl, C1-7alkoxy, halogen-C1-7alkoxy, phenoxy, halogen, C1-7alkylpiperazinyl-C1-7alkyl, C3-C8-cyclalkyl, C1-7alkylpiperidinyl-C1-7alkyl and C1-7alkylimidazolyl; R3 denotes H or phenyl-lower alkyl; R4 and R5 are independently selected from a group consisting of H; lower alkyl; lower alkoxy-carbonyl and amino; A, B and X are independently selected from C(R7) or N, provided that not more than one or A, B and X denotes N; R7 denotes H; R8 denotes hydrogen; n equals 0; Y denotes O; Z denotes C; W is absent; K denotes N or C, and either a) if K denotes C, the bond shown by a wavy line () is a double bond, Q is selected from O-N, S-N, O-CH and S-CH, where in each case, the left-hand O or S atom is bonded through a bond shown in formula I to K, the right-hand N or carbon (CH) atom is bonded to C through a bond shown by a dotted line () in formula I, provided that said bond, which is shown by the dotted line, is a double bond with C; and the bond shown by a thick line () is a single bond; or b) if K denotes N, the bond shown by a wavy line () is a single bond; Q denotes N=CH, where the left-hand N atom is bonded through a bond shown in formula I to K, the right-hand carbon (CH) atom is bonded to C through a bond shown by a dotted line () in formula I, provided that said bond, which is shown by a dotted line, is a single bond with C; and the bond shown by thick line () is a double bond; or salt thereof (preferably pharmaceutically acceptable salt). The invention also relates to a pharmaceutical composition, having inhibiting action on protein kinase, containing a compound of formula I or salt thereof in an effective amount and at least one pharmaceutically acceptable carrier material.

EFFECT: heterocyclic carboxamides as kinase inhibitors.

12 cl, 25 ex

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of general formula (I), in which (i) R1 denotes C1-C6-alkyl or hydrogen; and R2 denotes hydrogen or a -R7, -Z-Y-R7, -Z-NR9R10, -Z-CO-NR9R10, -Z-NR9-C(O)O-R7 or -Z-C(O)-R7 group; and R3 denotes an undefined pair or C1-C6-alkyl; or (ii) R1 and R3 together with a nitrogen atom with which they are bonded form a 5-6-member heterocycloalkyl ring; and R2 denotes an undefined pair or a -R7 , -Z-Y-R7 group; or (iii) R1 and R2 together with a nitrogen atom with which they are bonded form a 6-member heterocycloalkyl ring, where said ring is substituted with a -Y-R7 group, and R3 denotes an undefined pair or C1-C6-alkyl; R4 and R5 are independently selected from a group consisting of phenyl, C3-C6-cycloalkyl; R6 denotes -OH, C1-C6-alkyl, C1-C6-alkoxy or a hydrogen atom; A denotes an oxygen or sulphur atom; X denotes a C1-C6-alkylene group; R7 denotes C1-C6-alkyl, phenyl, phenyl(C1-C6-alkyl)-, dihydrobenzofuran or pyridine, where any phenyl in group R7 can be optionally substituted with one or two groups independently selected from halogen, aminoacyl, C1-C6-alkoxycarbonyl, aminosulphonyl, C1-C6-alkyl, C1-C6-alkylamino-C1-C6-alkyl, -COOH; and any pyridine in group R7 can be optionaly substituted with C1-C6-alkyl; R8 denotes C1-C6-alkyl or a hydrogen atom; Z denotes a C1-C10-alkylene or C2-C10-alkenylene group; Y denotes a bond or an oxygen atom; R9 and R10 independently denote a hydrogen atom, C1-C6-alkyl group, isoxazole or 8-hydroxy-1H-quinolin-2-one-(C1-C6-hydroxyalkyl); and pharmaceutically acceptable salts thereof. The invention also relates to a pharmaceutical composition having activity with respect to M3 muscarinic receptor; use of the compounds of formula (I) to produce a medicinal agent for treating and a method of treating diseases or conditions in which M3 muscarinic receptor activity is involved.

EFFECT: compounds of given formula have activity with respect to M3 muscarinic receptor.

26 cl, 8 dwg, 91 ex

7FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to a combination of a co-drug (an auxiliary) and a compound o formula (IV) in which radicals and symbols have the values defined in cl. 1 of the patent claim, or salts, or tautomers, or N-oxides, or solvates of this compound; where the specified auxiliary is specified from a monoclonal antibody, an alkylating agent, a malignant growth agent, other cycline-dependent kinase (CDK) inhibitor and a hormone, a hormone agonist, a hormone antagonist or a hormone-modulating agent specified in cl. 1 of the patent claim. The offered combination is used for tumour cell growth inhibition.

EFFECT: invention also refers to a pharmaceutical composition based on the offered combination, application of the combination and its separate ingredients and methods of treating, preventing and relieving the cancer symptoms in a patient.

77 cl, 2 dwg, 8 tbl, 257 ex

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of general formula where R denotes a thiazolyl group of formula R2 and R3 are selected from: hydrogen, C1-C3linear alkyl; R4 is selected from: C1-C3linear or C3cyclic alkyl, phenyl and thiophenyl; Z denotes a group of formula: -(L)n-R1; R1 is selected from: i) C1-C3linear or branched alkyl, optionally substituted with C1-C4alkoxycarbonyl, halogen; ii) substituted phenyl or substituted with one or two substitutes selected from halogen, methoxy- or hydroxy group, C1-C4alkoxycarbonyl; iii) dioxopiperazinyl and 2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl, substituted with C1-C3alkyl; or iv) heteroaryl rings containing 5-10 atoms selected from thiazole, triazole, 1H-imidazole, thiadiazole, oxazole, isoxazole, oxadiazole, benzodioxole, benzo(1,4)dioxepanyl, pyridine, pyrimidine, 1H-indole, 2,3-dihydrobenzo[b][1,4]dioxynil, which can be substituted with oine or two substitutes selected from: a) hydroxy; b) C1-C3alkyl (which can be substituted with one more two substitutes selected from: ) phenyl; ii) C1-C4alkoxycarbonyl; iii) naphthalenyl; iv) 2-methylthiazolyl) ; c) NHC(O)C1-C3alkyl; d) C1-C4alkoxycarbonyl; e) 1 -(tert-butoxycarbonyl)-2-phenylethyl; f) methoxybenzyl; g) phenyl which can be substuted with C1-C4alkoxy, halogen, methoxycarbonyl or >NHC(O)CH3; h) (methoxy-2-oxoethyl)carbamoyl; L denotes a group selected from: i) C(O)NH[C(R5aR5b)]w-; ii) -C(O)[C(R6aR6b)]x-; iii) -C(O)[C(R7aR7b)]yC(O)-; iv) -SO2[C(R8aR8b)]z-; R5a, R5b, R6a, R6b, R7a, R7b, R8a and R8b, each independently denotes: i) hydrogen; ii) C1-C3 linear alkyl which can be substituted with 1 or 2 halogen atoms; iii) phenyl which can be substituted with 1-2 substitutes selected from halogen and lower alkoxy; iv) heteroaryl rings selected from imidazolyl, imidazolyl substituted with methyl, benzo(1,4)oxazinyl, oxadiazolyl substituted with methyl; index n equals 0 or 1; indices w, x, y and z are each independently equal to a number from 1 to 3. The invention also relates to pharmaceutically acceptable salts of compounds of formula (I) and use of compounds of formula (I) to prepare a medicinal agent for treating protein tyrosine phosphatase beta-mediated conditions.

EFFECT: obtaining compounds of formula (I) as human protein tyrosine phosphatase beta (HPTP-β) inhibitors.

15 cl, 17 dwg, 13 tbl, 16 ex

FIELD: chemistry.

SUBSTANCE: invention relates to an isoxazoline-substituted benzamide derivative of formula or salt thereof, where A1 denotes a carbon or nitrogen atom, A2 and A3 independently denote a carbon atom, G denotes a benzene ring, W denotes an oxygen or sulphur atom, X denotes a halogen atom or C1-C6alkyl, arbitrarily substituted with a radical R4, Y denotes a halogen atom, cyano, nitro, C1-C6alkyl, C1-C6alkyl arbitrarily substituted with radical R4, -OR5, -N(R7)R6, phenyl, D-41, when n equals 2, each Y can be identical or different from each other, R1 denotes -C(R1b)=NOR1a, M-5, -C(O)OR1c, -C(O)SR1c, -C(S)OR1c, -C(S)SR1c, -C(O)N(R1e)R1d, -C(S)N(R1e)R1d, -C(R1d)=NN(R1e)R1lf, phenyl, phehnyl substituted with (Z)p1, or D-3, D-8, D-13-D-15, D-21, D-35, D-52-D-55 or D-57-D-59, R2 denotes C1-C6alkyl, -CH2R14a, E-5, C3-C6alkynyl, -C(O)R15, -C(O)OR15, -C(O)C(O)OR15 or -SR15, where, when R1 denotes -C(R1b)=NOR1a, M-5, or -C(R1b)=NN(R1e)R1f, R2 can denote a hydrogen atom, when R1 denotes -C(O)OR1c, -C(O)SR1c, -C(S)OR1c or -C(S)SR1c, R2 can denote hydrogen, when R denotes -C(O)N(R1e)R1d or -C(S)N(R1c)R1d, R2 can denote a hydrogen atom, when R1 denotes phenyl, phenyl substituted with (Z)p1, or D-3, D-8, -D-13-D-15, D-21, D-35, D-52-D-55 or D-57-D-59 R2 can denote C1-C6halogenalkyl, C1-C6alkyl arbitrarily substituted with a radical R14a, C3-C6alkenyl, -C(O)NH2, -C(O)N(R16)R15, or R2 together with R1 can form =C(R2b)R2a, R3 denotes C1-C6alkyl arbitrarily substituted with radical R4, D-1, D-3, D-8, D-13-D-15, D-21, D-35, D-41, D-52-D-55, D-57-D-59 denote aromatic heterocyclic rings, m equals an integer from 2 to 3, n equals an integer from 0 to 2.

EFFECT: isoxazoline-substituted benzamide derivative and salt thereof are used in pest control, against harmful arthropods in agriculture and horticulture or in livestock farming and in the field of hygiene.

12 cl, 18 tbl, 73 ex

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of formula I, where R1 denotes H; R6, R7, R8, R9, R10 independently denote H, F, Cl, Br, CF3, OCH3, OCF3, OCHF2, SCH3, SCF3, phenyl, (C1-C6)-alkyl, O-(C1-C6)-alkyl or NR3R4, where the alkyl and phenyl can be substituted with R2 once or many times, and where any two residues from R6, R7, R8, R9, R10 in neighbouring positions of the phenyl ring can form a -CH=CH-CH-CH- residue together; m equal 0, 1, 2 or 3; X denotes -(CH2)2-; R2 denotes F, Cl, Br, CN, OCH3, OCF3, CH3, CF3, (C1-C6)-alkyl or O-(C1-C6)-alkyl, where the alkyl can be substituted once or many times with OH, F, Cl, Br or CN; R3, R4 independently denote H or (C1-C6)-alkyl; or physiologically acceptable salts thereof, provided that the compound 3-(2-o- tolylamino-benzoxazol-6-yl)-propionic acid is excluded. The invention also relates to use of compounds of formula (I) to prepare a medicinal agent which activates GPR40 receptors and use of said compounds to prepare a medicinal agent for lowering blood sugar level, for treating diabetes and for increasing insulin secretion.

EFFECT: compounds of formula I which activate GPR40 receptors are obtained.

6 cl, 2 tbl, 146 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel compounds of formula (1), where A1, A2, A3, A4, A5 ad A6 are independently selected from a group comprising CR3 and N; provided that the biggest one of A1, A2, A , A4, A5 and A6 denotes N; B1, B2 and B3 are independently selected from a group comprising CR2 and N; each R3 independently denotes H or C1-C6 alkyl; and R1, R2, R4, R5, W and n are as given in the description, or salts thereof which are suitable for use in agriculture. The invention also relates to compositions containing compounds of formula (1), and insect-pest control methods which involve contact between the pest or habitat thereof with a biologically effective amount of the compound or composition according to the present invention, as well as to methods of protecting seeds and animals from insects-pests.

EFFECT: high effectiveness of the obtained compounds in insect-pest control.

29 cl, 12 tbl, 5 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a method of producing a compound of formula I: or salt thereof, where: y equals 0; R1 and R2 are taken together to form a 3-tetrahydrofuran ring; R9 is hydrogen; R10 is 5-oxazolyl; R11 is a methoxy-, ethoxy- or isopropoxy group; each V1 is independently selected from halogen, NO2, CN, OR12, OC(O)R13, OC(O)R12, OC(O)OR13, OC(O)OR12, OC(O)N(R13)2, OP(O)(OR13)2, SR13, SR12, S(O)R13, S(O)R12, SO2R13, SO2R12, SO2N(R13)2, SO2NR12R13, SO3R13, C(O)R12, C(O)OR12, C(O)R13, C(O)OR13, NC(O)C(O)R13, NC(O)C(O)R12, NC(O)C(O)OR13, NC(O)C(O)N(R13)2, C(O)N(R13)2, C(O)N(OR13)R13, C(O)N(OR13)R12, C(NOR13)R13, C(NOR13)R12, N(R13)2, NR13C(O)R12, NR13C(O)R13, NR13C(O)OR13, NR13C(O)OR12, NR13C(O)N(R13)2, NR13C(O)NR12R13, NR13SO2R13, NR13SO2R12, NR13SO2N(R13)2, NR13SO2NR12R13, N(OR13)R13, N(OR13)R12, P(O)(OR13)N(R13)2 and P(O)(OR13)2; where each R12 is a monocyclic or bicyclic ring system consisting of 5-6 members in each ring, where said ring system optionally contains up to 4 heteroatoms selected from N, O or S, and where CH2 lying next to said N, O or S can be substituted with C(O); and each R12 optionally contains up to 3 substitutes selected from R11; where each R13 is independently selected from H, (C1-C4)-straight or branched alkyl or (C2-C4)-straight or branched alkenyl; and where each R13 optionally contains a substitute which is R14; where R14 is a monocyclic or bicyclic ring system consisting of 5-6 members in each ring, where said ring system optionally contains up to 4 heteroatoms selected from N, O or S, and where CH2 lying next to said N, O or S can be substituted with C(O); and each R14 optionally contains up to 2 substitutes independently selected from H, (C1-C4)-straight or branched alkyl or (C2-C4)-straight or branched alkenyl, 1,2-methylenedioxy-, 1,2-ethylenedioxy group or (CH2)n-Z; where Z is selected from halogen, CN, NO2, CF3, OCF3, OH, S(C1-C4)alkyl, SO(C1-C4)alkyl, SO2(C1-C4)alkyl, NH2, NH(C1-C4)-alkyl, M((C1-C4)alkyl)2, COOH, C(O)O(C1-C4)alkyl or O(C1-C4)-alkyl; and where any carbon atom in any R13 is optionally substituted with O, S, SO, SO2, NH or N(C1-C4)alkyl; where said method includes a step for reacting a compound of formula II with a compound of formula III in a polar or nonpolar aprotic, virtually anhydrous solvent or mixture thereof, and optionally in an acceptable base selected from an organic base, inorganic base or a combination of an organic base and an inorganic base; and while heating the reaction mixture to temperature ranging from approximately 30°C to approximately 180°C for approximately 1 to 48 hours in a virtually inert atmosphere: where: LG is -OR16; where R16 is -(C1-C6)-straight or branched alkyl; -(C2-C6)-straight or branched alkenyl or alkynyl; or a monocyclic ring system consisting of 5-6 members in each ring, where said ring system optionally contains up to 3 heteroatoms selected from N, O or S, and each R16 optionally contains up to 5 substitutes independently selected from (C1-C4)-straight or branched alkyl, (C2-C4)-straight or branched alkenyl or (CH2)n-Z; n equals 0, 1, 2, 3 or 4; V1, y, Z, R1, R2, R9, R10 and R11 are as indicated above; and provided that R16 is not a halogen-substituted (C2-C3)-straight alkyl.

EFFECT: improved method.

19 cl, 1 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel compounds of formula

,

where: X is a nitrogen or carbon atom; Ar is phenyl or a heteroaromatic ring selected from pyrazolyl, furanyl, thiophenyl and isoxazolyl; R1 is hydrogen, halogen, CN or (C1-C4)alkyl; R2 is halogen or (C1-C3)alkoxy optionally fluorinated with 1-3 fluorine atoms; R3 and R5 independently denote hydrogen, (C1-C4)alkyl, (C1-C4)alkoxy, (C1-C4)alkenyl or hydroxymethyl; R4 is hydrogen, halogen, optionally fluorinated (C1-C4)alkoxy or aryl(C1-C4)alkoxy; R6 is hydrogen, optionally fluorinated (C1-C4)alkyl; each R7 independenlty denotes hydrogen, halogen, optionally fluorinated (C1-C4)alkyl or (C1-C4)alkoxy optionally fluorinated with 1-3 fluorine atoms; or pharmaceutically acceptable acid addition salts thereof. The invention also relates to use of compounds of formula (I) in a pharmaceutical composition and when preparing a medicinal agent meant for treatment, the aim of which is to change the secondary signal activity level after activation of glucocorticoid receptors.

EFFECT: compounds of formula I for changing the secondary signal activity level after activation of glucocorticoid receptors.

7 cl, 5 dwg, 49 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a novel C-phenyl glycitol compound which serves as a preventive or therapeutic agent for sugar diabetes by inhibiting SGLT1 activity, as well as SGLT2 activity; demonstrating inhibiting effect on glucose absorption, and also acts on release of glucose with urine. The C-phenyl glycitol compound has formula (I) given below, or pharmaceutically acceptable salt or hydrate thereof, where R1 and R2 are identical or different and denote a hydrogen atom, a hydroxyl group, a C1-6 alkyl group, a C1-6 alkoxy group or a halogen atom, R3 is a hydrogen atom, a C1-6 alkyl group or a C1-6 alkoxy group, Y is a C1-6 alkylene group, -O-(CH2)n- (n is a whole number which assumes values from 1 to 4), provided that when Z denotes -NHC(= NH)NH2 or -NHCON(RB)Rc, n not equal to 1, Z is -CONHRA, -NHC(=NH)NH2 or -NHCON(RB)Rc, or The invention also relates to a pharmaceutical composition based on compounds of formula I.

EFFECT: high efficiency of the compounds.

19 cl, 8 tbl

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