Benzopyrazine and benzoxepine pi3k inhibitors and use thereof

FIELD: chemistry.

SUBSTANCE: invention relates to a compound of formula I, including stereoisomers, geometric isomers, tautomers or pharmaceutically acceptable salts thereof: where Z1 is CR1; Z2 is CR2; Z3 is CR3 or N; Z4 is CR4 or N; where (i) X1 is N and X2 is S or (iv) X1 is S and X2 is CR7; R1, R2, R3, R4 and R7 are independently selected from H, F, Cl, Br, I, -CN, -CH2OR10, -(C1-C12 alkylene)NR10R11, -(C1-C12 alkylene)NR12C(=O)R10, -CO2R10, -C(=O)N(R10)OR11, -NR10R11, -C(=O)NR10R11, -C(=O)NR10(C1-C12 alkylene)NR10R11, -C(=O)NR10(C1-C12 alkylene)NR10C(=O)OR11, -C(=O)NR10(C1-C12 alkylene)NR10C(=O)R11, -C(=O)NR10(C1-C12 alkylene)R11, -C(=O)NR10(C1-C12 alkylene)R10, -C(=NR10)NR10R11, -NR12C(=O)R10, -NR12C(=O)OR11, -NR12C(-O)NR10R11, -NR12C(=O)(C1-C12 alkylene)NR10R11, NR12(C=O)C1-C12 alkylene)NR11(C=O)R12, -C≡CR10, C1-C20 heteroaryl, said heteroaryl being an unsaturated carbocyclic residue containing 5-6 ring atoms, where 1-4 ring atoms are nitrogen atoms, and phenyl, where the heteroaryl and phenyl are optionally substituted with one or two groups selected from -CH2OH, -(CH2)2OH, -CH2CO2H, -CN, -CH2NH2, -(CH2)2N(CH3)2, -CH3, -CO2H, -CH2CO2CH3, -NH2 and -S(O)2CH3; A is selected from -C(=O)NR5R6, -C(=S)NR5R6, phenyl and C1-C20 heteroaryl, said heteroaryl being an unsaturated carbocyclic residue containing 5-10 ring atoms, 1-4 of which are heteroatoms selected from nitrogen, oxygen or sulphur, C1-C20 heteroaryl and phenyl are optionally substituted with one or three groups independently selected from C1-C12 alkyl, -(C1-C12 alkylene)NR10R11, -CH3, oxo, -CO2CH3, -NH2, 1-methylpiperid-4-yl, isopropyl, isobutyl, cyclopropyl, cyclopropylmethyl, cyclobutyl, benzoimidazolyl, benzyl and phenyl, where the alkyl, benzoimidazolyl and phenyl are optionally substituted with one or more groups independently selected from F, Cl, Br, I, -CF3, -CH2OH, -CH3, -C(=O)NHCH3, -NH2, -OH, -OCH3, -CH2OCH3, -C(=O)N(CH3)2, -N(CH3)2, -C(CH3)2OH, -CH(CH3)2, -CH2(1H-1,2,4-triazol-5-yl) and C(=O)4-methylpiperazin-1-yl; R5 is selected from C1-C12 alkyl, optionally substituted with one group independently selected -NH2, -NHCOCH3 and -OH; R6 is selected from pyridinyl and phenyl, each optionally substituted with one or two groups independently selected from F, Cl, Br, I, -CN, -CF3, -C(=O)NR10R11, -C(=O)NR10(C1-C12 alkylene)NR10R11 and -C(=O)NR10R11; R10, R11 and R12 are independently selected from H, C1-C12 alkyl, C1-C12 alkylene-phenyl, cyclopentyl, pyridinyl and imidazolyl, where C1-C12 alkyl, cyclopentyl are optionally substituted with one or two groups independently selected from -CH2OH, -N(CH3)2, -NHCOCH3, -OH and -S(O)2CH3; or R10 and R11 together with a nitrogen atom to which they are bonded form a C5-C6 heterocyclic ring containing one or two heteroatoms selected from nitrogen and oxygen, or pyrazolyl, optionally substituted with one or two groups independently selected -CH3, -NH2, -N(CH3)2; -OH and oxo. The invention also relates to a pharmaceutical composition having PI3K inhibiting activity based on said compounds.

EFFECT: obtaining novel compounds which can be used in medicine for treating cancer.

25 cl, 5 dwg, 2 tbl, 331 ex

 

The text descriptions are given in facsimile form.

1. A compound selected from compounds of the Formula I:
,
where
Z1represents CR1;
Z2represents CR2;
Z3represents CR3or N;
Z4represents CR4or N;
where (i) X1represents N and X2represents S or (iv) X1represents S and X2represents CR7;
R1, R2,R 3, R4and R7independently selected from H, F, Cl, Br, I, -CN, -CH2OR10, -(C1-C12alkylen)NR10R11, -(C1-C12alkylen)NR12C(=O)R10, -COR10, -C(=O)N(R10OR11, -NR10R11, -C(=O)NR10R11, -C(=O)NR10(C1-C12alkylen)NR10R11, -C(=O)NR10(C1-C12alkylen)NR10C(=O)OR11, -C(=O)NR10(C1-C12alkylen)NR10C(=O)R11, -C(=O)NR10(C1-C12alkylene)R11, -C(=O)NR10(C1-C12alkylene)R10, -C(=NR10)NR10R11, -NR12C(=O)R10, -NR12C(=O)OR11, -NR12C(=O)NR10R11, -NR12C(=O) (C1-C12alkylen)NR10R11, NR12(C=O)1-C12alkylen)NR11(C=O)R12, -C≡CR10C1-C20heteroaryl, specified heteroaryl is an unsaturated carbocyclic residue containing 5 to 6 ring atoms, of which 1-4 of the ring atoms are nitrogen, and phenyl, where heteroaryl and phenyl may have as substituents one or two group selected from-CH2OH, -(CH2)2OH, -CH2CO2H, -CN, -CH2NH2, -(CH2)2N(CH3)2, -CH3, -CO2H, -CH2CO2CH3, -NH2and-S(O)2CH3;
A is selected from-C(=O)NR5R6, -C(=S)R 5R6and C1-C20heteroaryl, specified heteroaryl is an unsaturated carbocyclic residue containing 5-10 ring atoms, of which 1-4 of the ring atoms are heteroatoms selected from nitrogen, oxygen and sulfur, where C1-C20heteroaryl may have as substituents one or three groups independently selected from F, C1-C12of alkyl, -(C1-C12alkylen)NR10R11, -CH3, oxo, -CO2CH3, -NH2, 1-methylpiperid-4-yl, isopropyl, isobutyl, cyclopropyl, cyclopropylmethyl, cyclobutyl, benzoimidazolyl, benzyl and phenyl, where the alkyl, benzoimidazolyl and phenyl may have as substituents one or more groups independently selected from F, Cl, Br, I, -CF3, -CH2HE, -CH3-C(=O)NHCH3, -NH2, -OH, -och3, -CH2Och3-C(=O)N(CH3)2, -N(CH3)2, -(CH3)2HE, -CH(CH3)2, -CH2(1H-1,2,4-triazole-5-yl) and C(=O)4-methylpiperazin-1-yl;
R5selected from C1-C12the alkyl may contain as a substituent one group independently selected from-NH2, -NHCOCH3and HE;
R6selected from pyridinyl and phenyl, each of which may have as substituents one or two groups independently selected from F, Cl, Br, I, -CN, -CF3 , -C(=O)NR10R11, -C(=O)NR10(C1-C12alkylen)NR10R11and-C(=O)NR10R11;
R10, R11and R12independently selected from H, C1-C12of alkyl, C1-C12alkylen-phenyl, cyclopentyl, pyridinyl and imidazolyl, where C1-C12alkyl, cyclopentyl may have as substituents one or two groups independently selected from-CH2HE, -N(CH3)2, -NHCOCH3-HE and-S(O)2CH3;
or R10and R11together with the nitrogen atom to which they are attached, form a5-C6heterocyclic ring containing one or two heteroatoms, selected from nitrogen and oxygen, or pyrazolyl may contain as substituents one or two groups independently selected from-CH3, -NH2, -N(CH3)2HE and oxo;
and stereoisomers, geometric isomers, tautomers or pharmaceutically acceptable salt.

2. The compound according to claim 1, where
Z1represents CR1;
Z2represents CR2;
Z3represents CR3or N;
Z4represents CR4or N;
where (i) X1represents N and X2represents S or (iv) X1represents S and X2represents CR7;
R1, R2, R3, R4and R72OR10, -(C1-C12alkylen)NR10R11, -(C1-C12alkylen)NR12C(=O)R10, -CO2R10, -C(=O)N(R10OR11, -NR10R11, -C(=O)NR10R11, -C(=O)NR10(C1-C12alkylen)NR10R11, -C(=O)NR10(C1-C12alkylen)NR10C(=O)OR11, -C(=O)NR10(C1-C12alkylen)NR10C(=O)R11, -C(=O)NR10(C1-C12alkylene)R10, -C(=NR10)NR10R11, -NR12C(=O)R10, -NR12C(=O)OR11, -NR12C(=O)NR10R11, -NR12(C=O) (C1-C12alkylen)NR10R11, NR12(C=O)C1-C12alkylen)NR11(C=O)R12, -C≡CR10C1-C20heteroaryl, specified heteroaryl is an unsaturated carbocyclic residue containing 5 to 6 ring atoms, of which 1-4 of the ring atoms are nitrogen, and phenyl, where heteroaryl and phenyl may have as substituents one or two group selected from-CH2HE, -(CH2)2OH, -CH2CO2H, -CN, -CH2NH2, -(CH2)2N(CH3)2, -CH3, -CO2H, -CH2CO2CH3, -NH2and-S(O)2CH3;
A is selected from-C(=O)NR5R6and C1-C20heteroaryl, specified heteroaryl is an unsaturated who arboricides residue, containing 5-10 ring atoms, of which 1-4 of the ring atoms are heteroatoms selected from nitrogen, oxygen and sulfur, where C1-C20heteroaryl may have as substituents one or three groups independently selected from F, C1-C12of alkyl, -(C1-C12alkylen)NR10R11, -CH3, oxo, -CO2CH3, -NH2, 1-methylpiperid-4-yl, isopropyl, isobutyl, cyclopropyl, cyclopropylmethyl, cyclobutyl, benzyl and phenyl, where alkyl and phenyl may have as substituents one or more groups independently selected from F, CI, Br, I, -CF3, -CH2OH, -CH3-C(=O)NHCH3, -NH2, -OH, -och3and CH2(1H-1,2,4-triazole-5-yl);
R5selected from C1-C12the alkyl may contain as a substituent one group independently selected from-NH2, -NHCOCH3and HE;
R6selected from pyridinyl and phenyl, each of which may have as substituents one or two groups independently selected from F, Cl, Br, I, -CN, -CF3, -C(=O)NR10R11-C(=O)NR10(C1-C12alkylen)NR10R11and-C(=O)NR10R11;
R10, R11and R12independently selected from H, C1-C12of alkyl, C1-C12alkylen-phenyl, cyclopentyl, pyridinyl and imidazolyl, where C1-C12alkyl, cyclopent the l may have as substituents one or two groups, independently selected from-CH2OH, -N(CH3)2, -NHCOCH3-HE and-S(O)2CH3;
or R10and R11together with the nitrogen atom to which they are attached, form a C5-C6heterocyclic ring containing one or two heteroatoms, selected from nitrogen and oxygen, or pyrazolyl may contain as substituents one or two groups independently selected from-CH3, -N(CH3)2HE and oxo.

3. The compound according to claim 1, where X1represents N and X2represents S.

4. The compound according to claim 1, where X1represents S and X2represents CR7.

5. The compound according to claim 1, selected from the following structures

6. The compound according to claim 1, selected from the following structures

7. The compound according to claim 1 selected from the following structures:

.

8. The compound according to claim 1 selected from the following structures:
,
where each of R1, R3and R4represents N and R2selected from F, Cl, Br, I, -CN, -CH2OR10, -CH2NR10R11, -CO2R10, -C(=ON(R 10OR11, -NR10R11, -C(=O)NR10R11, -C(=O)NR10(C1-C12alkylen)NR10R11, -C(=O)NR10(C1-C12alkylen)NR10C(=O)OR11, -C(=O)NR10(C1-C12alkylen)NR10C(=O)R11, -C(=O)NR10(C1-C12alkylene)R10, -NR12C(=O)R10, -NR12C(=O)OR11, -NR12C(=O)NR10R11, -NR12(C1-C12alkylen)NR10R11, -C≡CR10C1-C20heteroaryl, specified heteroaryl is an unsaturated carbocyclic residue containing 5 to 6 ring atoms, of which 1-4 of the ring atoms are nitrogen, and phenyl, where heteroaryl and phenyl may have as substituents one or two groups selected from-CH2HE, -CH2CO2H, -CN, -CH2NH2, -CH3, -CH2CO2CH3; -NH2, -S(O)2CH3.

9. The compound according to claim 1, where R5represents CH3.

10. The compound according to claim 1, where R6represents phenyl, containing as substituents one or more groups independently selected from F, Cl, Br, I, -CN, -CF3, -CONH2, -CONHCH3.

11. The compound according to claim 1, where a represents a C1-C20heteroaryl selected from pyridyl, isoxazolyl, imidazolyl, pyrazolyl, pyrrolyl, thiazolyl, pyrimidinyl, pyrazinyl, cazalilla, oxadiazolyl, 1,3,4-oxadiazol-2(3H)-she 1,2,3-triazolyl, 1,2,4-triazolyl, 1,2,4-triazole-5(4H)-she 4,5-dihydro-1,2,4-triazine-6(1H)-she tetrazolyl, pyrrolo[2,3-b]pyridinyl, indazole.

12. The compound according to claim 1, where a is selected from the following structures:





where R8and R9independently selected from H, F, -CH3, -NH2, 1-methylpiperid-4-yl, isopropyl, isobutyl, benzyl and phenyl, where phenyl may have as substituents one or more than one group selected from F, CI, Br, I, -CH2HE, -CH3-C(=O)NHCH3, -NH2, 4-methylpiperazin-1-yl.

13. The connection section 12, where a is selected from the following structures:








where the wavy line indicates the place of attachment.

14. The compound according to claim 1, selected from
N2-(2-chlorophenyl)-N2,N8,N8-trimethyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2,8-dicarboxamide;
7-acetamido-N-(2-chlorophenyl)-N-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2-carboxamide;
N2-(2-chlorophenyl)-N8-(3-(diethylamino)propyl)-N2-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2,8-dicarboxamide;
N-(2-chlorophenyl)-7-cyano-N-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2-carboxamide;
5-(4,5-dihydropyrido[4,3-b]thieno[2,3-d]oxepin-2-yl)pyridine-2-amine;
N-(2-chlorophenyl)-N-(2-hydroxyethyl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2-carboxamide;
N-(2-chloro-4-forfinal)-N-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2-carboxamide;
N-(2,4-dichlorophenyl)-N-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2-carboxamide;
methyl 5-(6,7-dihydropyrido[3,2-b]thieno[2,3-d]oxepin-9-yl)2-aminosalicylate;
2-(4-isopropyl-5-oxo-4,5-dihydro-1H-1,2,4-triazole-3-yl)-4,5-dihydrobenzo[b]is ieno[2,3-d]oxepin-8-carboxamide;
8-bromo-4,5-dihydro-6-oxa-3-thia-1-Aza-benzo[e]azulene-2-carboxylic acid (2-chloro-4-methylcarbamoyl-phenyl)-methyl-amide;
1-(2-(4-(2-chlorophenyl)-4H-1,2,4-triazole-3-yl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-8-yl)-3-metallocene;
methyl 2-(4-(2-chlorophenyl)-4H-1,2,4-triazole-3-yl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-8-ylcarbamate;
7-bromo-N-(2-chlorophenyl)-N-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2-carboxamide;
N-(2-(4-(2-chlorophenyl)-4H-1,2,4-triazole-3-yl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-8-yl)ndimethylacetamide;
N-(4-(3-amino-5-methyl-1H-pyrazole-1-carbonyl)-2-chlorophenyl)-N-(2-hydroxyethyl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2-carboxamide;
N-(4-(2-acetamidoacrylic)-2-chlorophenyl)-N-(2-hydroxyethyl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2-carboxamide;
N-(2-chloro-4-((2-(dimethylamino)ethyl)(methyl)carbarnoyl)phenyl)-N-(2-hydroxyethyl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2-carboxamide;
N2-(2-chlorophenyl)-N2-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2,9-dicarboxamide;
N-(2-chlorophenyl)-9-cyano-N-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2-carboxamide;
4,5-dihydro-6-oxa-3-thia-1-Aza-benzo[e]azulene-2-carboxylic acid (2-chloro-4-methylcarbamoyl-phenyl)-methyl-amide;
N-(2-chlorophenyl)-N-methyl-8-(pyridin-3-yl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2-carboxamide;
N-(2-chlorophenyl)-N-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2-thioamide group by forming;
8-(3-AMINOPHENYL)-N-(2-chlorophenyl)-N-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]OK who EPIN-2-carboxamide;
N-(2-chlorophenyl)-8-(3-(dimethylamino)prop-1-inyl)-N-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2-carboxamide;
N-(2-chlorophenyl)-8-(3-hydroxyprop-1-inyl)-N-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2-carboxamide;
4-(6,7-dihydropyrido[3,2-b]thieno[2,3-d]oxepin-9-yl)-(2-chlorophenyl)-2-atsetamino-1H-imidazole;
4-(6,7-dihydropyrido[3,2-b]thieno[2,3-d]oxepin-9-yl)-(2-chlorophenyl)-2-amino-1H-imidazole;
4-(6,7-dihydropyrido[3,2-b]thieno[2,3-d]oxepin-9-yl)-(5-(2-chlorophenyl))-oxazole;
N-methyl-N-(2-(trifluoromethyl)phenyl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2-carboxamide;
N-(2-amino-ethyl)-N-(2-chlorophenyl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2-carboxamide;
N-(2-chlorophenyl)-N-methyl-8-(1H-pyrazole-4-yl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2-carboxamide;
N-(2-chlorophenyl)-8-ethinyl-N-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2-carboxamide;
N-(2-chlorophenyl)-N-methyl-8-(pyridin-4-yl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2-carboxamide;
N-(2-chlorophenyl)-N-methyl-8-phenyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2-carboxamide;
5-(4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2-yl)-1H-pyrrolo[2,3-b]pyridine;
N2-(2-chlorophenyl)-N2-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2,8-dicarboxamide;
methyl 2-((2-chlorophenyl)(methyl)carbarnoyl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-8-carboxylate;
tert-butyl 2-(2-((2-chlorophenyl)(methyl)carbarnoyl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-8 carboxamido)ethyl(methyl)carbamate;
4-(4,5-dihydrobenzo[b]Tien is[2,3-d]oxepin-2-yl)-1H-indazole;
N-(2-chlorophenyl)-N-methyl-(10-cyano-4,5-dihydropyrido-[4,3-b]thieno[2,3-d]oxepin-2)-carboxamide;
5-(6,7-dihydropyrido[3,2-b]thieno[2,3-d]oxepin-9-yl)pyridine-2-amine;
N-(2-chlorophenyl)-8-cyano-N-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2-carboxamide;
3-(2-((2-chlorophenyl)(methyl)carbarnoyl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-8-yl)benzoic acid;
N-(2-chlorophenyl)-N-methyl-8-(morpholine-4-carbonyl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2-carboxamide;
N-(2-chlorophenyl)-N-methyl-8-(3-(methylsulphonyl)phenyl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2-carboxamide;
8-acetamido-N-(2-chloro-4-(4-methylpiperazin-1-carbonyl)phenyl)-N-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2-carboxamide;
N2-(2-chlorophenyl)-N2,N8-dimethyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2,8-dicarboxamide;
methyl 2-((2-chlorophenyl)(methyl)carbarnoyl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-8-ylcarbamate;
8-bromo-N-(2-chlorophenyl)-N-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2-carboxamide;
8-acetamido-N-(2-chlorophenyl)-N-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2-carboxamide;
3-(4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2-yl)pyridine;
4-(4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2-yl)pyridine;
N2-(2-chlorophenyl)-N2-(2-hydroxyethyl)-N8-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2,8-dicarboxamide;
N2-(4-chloropyridin-3-yl)-N2,N8-dimethyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2,8-dicarboxamide;
N-(2,4-differenl)-N-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-carboxamide;
N-(2-chlorophenyl)-N-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2-carboxamide;
N-(2-chlorophenyl)-8-(2-hydroxyacetamido)-N-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2-carboxamide;
N-(2-chloro-4-(methylcarbamoyl)phenyl)-N-(2-hydroxyethyl)-10-Aza-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2-carboxamide;
N-(2-chloro-4-(4-methylpiperazin-1-carbonyl)phenyl)-N-(2-hydroxyethyl)-10-Aza-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2-carboxamide;
N-(2-chlorophenyl)-8-(3-(dimethylamino)propanamide)-N-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2-carboxamide;
N-(2-chlorophenyl)-N-methyl-4,5-dihydropyrido[4,3-b]thieno[2,3-d]oxepin-2-carboxamide;
5-(4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2-yl)pyrimidine-2-amine;
3-(6,7-dihydropyrido[3,2-b]thieno[2,3-d]oxepin-9-yl)-4-(2-chlorophenyl)-4H-1,2,4-triazole;
4-(6,7-dihydropyrido[3,2-b]thieno[2,3-d]oxepin-9-yl)-(5-(2-chlorophenyl)-thiazol-2-amine;
N-(2-chlorophenyl)-8-(3-ethylurea)-N-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2-carboxamide;
N-(2-chlorophenyl)-N-methyl-8-(3-methylurea)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2-carboxamide;
N-(2-chlorophenyl)-N-methyl-8-ureido-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2-carboxamide;
N-(2-chlorophenyl)-8-(2-(diethylamino)acetamido)-N-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2-carboxamide;
N-(2-chlorophenyl)-N-methyl-8-(2-morpholinoethyl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2-carboxamide;
N-(2-chlorophenyl)-N-methyl-8-(2-(4-methylpiperazin-1-yl)acetamido)-4,5-digidrive the AOR[b]thieno[2,3-d]oxepin-2-carboxamide;
(3-chloro-4-(3-(4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2-yl)-4H-1,2,4-triazole-4-yl)phenyl)(4-methylpiperazin-1-yl)methanone;
N2-(2-chlorophenyl)-N2-methyl-8-(pyridine-3-ylmethyl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2,8-dicarboxamide;
N2-(2-chlorophenyl)-N8-(1-(hydroxymethyl)cyclopentyl)-N2-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2,8-dicarboxamide;
N2-(2-chlorophenyl)-N8-((S)-1-hydroxy-3,3-dimethylbutan-2-yl)-N2-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2,8-dicarboxamide;
N-(2-chlorophenyl)-8-(4-hydroxypiperidine-1-carbonyl)-N-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2-carboxamide;
N2-(2-chlorophenyl)-N8-((S)-2-hydroxypropyl)-N2-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2,8-dicarboxamide;
N2-(2-chlorophenyl)-N8-((S)-1-hydroxypropan-2-yl)-N2-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2,8-dicarboxamide;
N2-(2-chloro-4-(methylcarbamoyl)phenyl)-N2,N8-dimethyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2,8-dicarboxamide;
N-(2-chloro-4-(methylcarbamoyl)phenyl)-8-cyano-N-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2-carboxamide;
N2-(2-chloro-4-(4-methylpiperazin-1-carbonyl)phenyl)-N2,N8-dimethyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2,8-dicarboxamide;
N-(2-chloro-4-(4-methylpiperazin-1-carbonyl)phenyl)-8-cyano-N-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2-carboxamide;
N-(3-chloropyridin-4-yl)-N-methyl-8-(1H-pyrazole-4-yl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2-carboxamide;
N-(3-chloropyridin-4-yl)-N-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]accepi the-2-carboxamide;
N8-(2-amino-ethyl)-N2-(2-chlorophenyl)-N2-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2,8-dicarboxamide;
N8-(2-acetamidomethyl)-N2-(2-chlorophenyl)-N2-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2,8-dicarboxamide;
N2-(2-chlorophenyl)-N2-methyl-8-(2-(methylamino)ethyl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2,8-dicarboxamide;
N2-(2-chlorophenyl)-8-methoxy-N2,N8-dimethyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2,8-dicarboxamide;
N-(2-chlorophenyl)-8-methoxy-N-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2,8-dicarboxamide;
N-(2-chlorophenyl)-8-(hydroxymethyl)-N-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2-carboxamide;
N-(2-chloro-4-(1-hydroxypropan-2-ylcarbonyl)phenyl)-N,10-dimethyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2-carboxamide;
N-(2-chloro-4-(2-hydroxypropylamino)phenyl)-N-methyl(10-Aza-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin)-2-carboxamide;
N-(2-chloro-4-(piperazine-1-carbonyl)phenyl)-N-methyl(10-Aza-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin)-2-carboxamide;
N8-(3-(1H-imidazol-1-yl)propyl)-N2-(2-chlorophenyl)-N2-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2,8-dicarboxamide;
N8-(2-amino-2-methylpropyl)-N2-(2-chlorophenyl)-N2-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2,8-dicarboxamide;
8-(3-(aminomethyl)phenyl)-N-(2-chlorophenyl)-N-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2-carboxamide;
N-(2-chlorophenyl)-8-((2-(dimethylamino)ethylamino)methyl)-N-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2-carboxamide;
2-(3-(2-((2-chlorophenyl)(methyl)ka is bemail)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-8-yl)phenyl)acetic acid;
N-(2-chlorophenyl)-8-(3-cyanophenyl)-N-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2-carboxamide;
methyl 2-(3-(2-((2-chlorophenyl)(methyl)carbarnoyl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-8-yl)phenyl)acetate;
N-(2-chlorophenyl)-8-(3-(hydroxymethyl)phenyl)-N-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2-carboxamide;
N-(2-chlorophenyl)-N-methyl-8-(4-methylpiperazin-1-carbonyl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2-carboxamide;
N2-(2-chlorophenyl)-N2-methyl-8-(2-(4-methylpiperazin-1-yl)ethyl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2,8-dicarboxamide;
N2-(2-chlorophenyl)-N8-(2-(dimethylamino)ethyl)-N2-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2,8-dicarboxamide;
N2-(2-chlorophenyl)-8-isopropyl-N2-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2,8-dicarboxamide;
N2-(2-chlorophenyl)-N8-ethyl-N2-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2,8-dicarboxamide;
N-(3-chloropyridin-2-yl)-N-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2-carboxamide;
N-methyl-N-(4-(trifluoromethyl)pyridin-3-yl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2-carboxamide;
3-chloro-4-(3-(4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2-yl)-4H-1,2,4-triazole-4-yl)-N-methylbenzamide;
N-(2-chlorophenyl)-8-(2-(dimethylamino)acetamido)-N-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2-carboxamide;
8-(2-acetamidoacrylic)-N-(2-chlorophenyl)-N-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2-carboxamide;
3-(8-(1H-pyrazole-4-yl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2-yl)-4,5-dihydro-1,2,4-triazine-6(1H)-she;
N-(2-chloro-4-(methylcarbamoyl)phenyl)-N-methyl(10-Aza, 4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2-carboxamide;
N-(2-chloro-4-(dimethylcarbamoyl)phenyl)-N-methyl(10-Aza, 4,5-dihydrobenzo[b]thieno[2,3-d]oxepin)-2-carboxamide;
N-(2-chloro-4-(4-methylpiperazin-1-carbonyl)phenyl)-N-methyl(10-Aza-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin)-2-carboxamide;
2-(2-amino-5-(2-chlorophenyl)thiazol-4-yl)-N-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-8-carboxamide;
2-(4-(2-chlorophenyl)-5-methyl-4H-1,2,4-triazole-3-yl)-N-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-8-carboxamide;
N-(4-chloropyridin-3-yl)-N-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2-carboxamide;
N-(2-chloro-4-(dimethylcarbamoyl)phenyl)-N-(2-hydroxyethyl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2-carboxamide;
N-(2-chloro-4-(4-methylpiperazin-1-carbonyl)phenyl)-N-(2-hydroxyethyl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2-carboxamide;
N2-(2-chloro-4-(piperazine-1-carbonyl)phenyl)-N2,N8-dimethyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2,8-dicarboxamide;
N2-(2-chloro-4-(dimethylcarbamoyl)phenyl)-N2,N8-dimethyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2,8-dicarboxamide;
3-(8-bromo-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2-yl)-4-isopropyl-4H-1,2,4-triazole;
3-(4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2-yl)-4-(1-methylpiperidin-4-yl)-1H-1,2,4-triazole-5(4H)-she;
4,5-dihydro-6-oxa-3-thia-1-Aza-benzo[e]azulene-2-carboxylic acid (2-chloro-phenyl)-methyl-amide;
N-(2-chloro-4-(2-hydroxypropylamino)phenyl)-N-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2-carboxamide;
N - (2-chloro-4-(1-hydroxypropan-2-ylcarbonyl)phenyl)-N-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2-carboxamide;
N-(4-(3-(1H-imidazol-1-yl)propellerblades)-2-chlorophenyl)-N-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2-carboxamide;
N-(4-(2-acetamidoacrylic)-2-chlorophenyl)-N-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2-carboxamide;
N-(2-chloro-4-(isopropylcarbamate)phenyl)-N-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2-carboxamide;
N-(2-chloro-4-(dipropylamino)phenyl)-N-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2-carboxamide;
8-bromo-N-(2-chlorophenyl)-N-(2-hydroxyethyl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2-carboxamide;
2-(4-(2-chlorophenyl)-4H-1,2,4-triazole-3-yl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-8-carboxylic acid;
2-(4-(2-chlorophenyl)-4H-1,2,4-triazole-3-yl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-8-amine;
N-(2-(4-(2-chlorophenyl)-4H-1,2,4-triazole-3-yl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-8-yl)-2-morpholinoethyl;
N-(2-(4-(2-chlorophenyl)-4H-1,2,4-triazole-3-yl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-8-yl)-2-(dimethylamino)ndimethylacetamide;
N-(2-amino-2-methylpropyl)-2-(4-(2-chlorophenyl)-4H-1,2,4-triazole-3-yl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-8-carboxamide;
2-(4-(2-chlorophenyl)-4H-1,2,4-triazole-3-yl)-N-ethyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-8-carboxamide;
2-(4-(2-chlorophenyl)-4H-1,2,4-triazole-3-yl)-N-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-8-carboxamide;
N-(2-chlorophenyl)-N-methyl-8-((4-methylpiperazin-1-yl)methyl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2-carboxamide;
N-(2-chlorophenyl)-8-((dimethylamino)methyl)-N-methyl-4,5-dihyd is ebenso[b]thieno[2,3-d]oxepin-2-carboxamide;
N-(2-chlorophenyl)-N-methyl-8-((methylamino)methyl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2-carboxamide;
8-(aminomethyl)-N-(2-chlorophenyl)-N-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2-carboxamide;
4-benzyl-3-(4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2-yl)-1H-1,2,4-triazole-5(4H)-she;
N-(2,6-dichlorophenyl)-N-methyl-(10-Aza-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2-carboxamide;
N-(2,4-dichlorophenyl)-9-(4-(dimethylamino)piperidine-1-carbonyl)-N-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2-carboxamide;
N-(2-chloro-4-(2-(dimethylamino)ethylcarbamate)phenyl)-N-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2-carboxamide;
N-(2-chloro-4-(dimethylcarbamoyl)phenyl)-N-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2-carboxamide;
N-(2-chloro-4-(methylcarbamoyl)phenyl)-N-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2-carboxamide;
N-(2-chloro-4-(morpholine-4-carbonyl)phenyl)-N-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2-carboxamide;
N-(2-chloro-4-(4-methylpiperazin-1-carbonyl)phenyl)-N-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2-carboxamide;
N-(2-chloro-4-(piperazine-1-carbonyl)phenyl)-N-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2-carboxamide;
3-(4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2-yl)-4-(1-hydroxypropan-2-yl)-1H-1,2,4-triazole-5(4H)-she;
3-(9-bromo-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2-yl)-4-(2,4-dichlorophenyl)-4H-1,2,4-triazole;
4-(2-chlorophenyl)-3-(10-Aza-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2-yl)-1 H-1,2,4-triazole-5(4H)-she;
3-(4,5-dihydrobenzo[b]is ieno[2,3-d]oxepin-2-yl)-4-(1-methoxypropan-2-yl)-1H-1,2,4-triazole-5(4H)-it;
N-(2-acetamidomethyl)-N-(2-chlorophenyl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2-carboxamide;
2-(4-isopropyl-5-oxo-4,5-dihydro-1H-1,2,4-triazole-3-yl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-8-carbonitrile;
3-(4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2-yl)-4-isobutyl-1H-1,2,4-triazole-5(4H)-she;
N-(2-chlorophenyl)-N-methyl-8-(morpholinomethyl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2-carboxamide;
4-(8-(1H-pyrazole-4-yl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2-yl)-5-(2-chlorophenyl)thiazol-2-amine;
N-(2-chlorophenyl)-N-methyl-(10-Aza-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2-carboxamide;
3-(8-(1H-pyrazole-4-yl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2-yl)-4-isopropyl-1H-1,2,4-triazole-5(4H)-she;
3-(8-bromo-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2-yl)-4-isopropyl-1H-1,2,4-triazole-5(4H)-she;
5-(8-bromo-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2-yl)-1,3,4-oxadiazol-2(3H)-she;
3-(9-bromo-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2-yl)-4-(2-chloro-4-forfinal)-4H-1,2,4-triazole;
2-(2-amino-5-(2-chlorophenyl)thiazol-4-yl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-8-carboxamide;
3-(8-(1H-pyrazole-4-yl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2-yl)-4-ethyl-1H-1,2,4-triazole-5(4H)-she;
2-(4-(2-chlorophenyl)-4H-1,2,4-triazole-3-yl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-8-carboxamide;
4-(8-bromo-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2-yl)-5-(2-chlorophenyl)thiazol-2-amine;
3-(8-bromo-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2-yl)-4-(2-chlorophenyl)-5-methyl-4H-1,2,4-triazole;
3-(8-bromo-4,5-dihydrobenzo[b]thieno[2,3-d]oaks is in-2-yl)-4-(2-chlorophenyl)-4H-1,2,4-triazole;
2-(4-(2-chlorophenyl)-1H-pyrazole-3-yl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-8-carboxamide;
2-(4-(2-chlorophenyl)-1H-pyrazole-3-yl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-8-carbonitrile;
3-(8-bromo-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2-yl)-4-(2-chlorophenyl)-1H-pyrazole;
3-(8-(1H-pyrazole-4-yl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2-yl)-4-(2-chlorophenyl)-1H-1,2,4-triazole-5(4H)-she;
2-(4-(2-chlorophenyl)-5-oxo-4,5-dihydro-1H-1,2,4-triazole-3-yl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-8-carbonitrile;
3-(8-bromo-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2-yl)-4-(2-chlorophenyl)-1H-1,2,4-triazole-5(4H)-she;
5-(2-chlorophenyl)-4-(4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2-yl)thiazol-2-amine;
2-(4-(2-chloro-4-forfinal)-4H-1,2,4-triazole-3-yl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-9-carboxamide;
5-(2-chlorophenyl)-4-(4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2-yl)pyrimidine-2-amine;
4-(2-chlorophenyl)-3-(4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2-yl)-1H-pyrazole;
4-(2-chlorophenyl)-3-(4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2-yl)-1H-1,2,4-triazole-5(4H)-she;
2-(1-(2-chlorophenyl)-1H-tetrazol-5-yl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-8-carboxamide;
5-(8-bromo-4,5-dihydrobenzo[b]thieno[2,3d]oxepin-2-yl)-1-(2-chlorophenyl)-1H-tetrazole;
5-(8-bromo-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2-yl)-4-(2-chlorophenyl)-4H-1,2,4-triazole-3-amine;
N2-(2,4-dichlorophenyl)-N2,N9,N9-trimethyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2,9-dicarboxamide;
3-(9-bromo-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2-yl)-4-(2-chloro-4-(trifluoromethyl)f the Nile)-4H-1,2,4-triazole;
N-(2-chloro-4-forfinal)-9-cyano-N-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2-carboxamide;
9-cyano-N-(2,4-differenl)-N-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2-carboxamide;
4-(2-chloro-6,7-dihydropyrido[3,2-b]thieno[2,3-d]oxepin-9-yl)-5-(2-chlorophenyl)-2H-1,2,3-triazole;
3-(9-bromo-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2-yl)-4-(2,4-differenl)-4H-1,2,4-triazole;
5-(2-chloro-6,7-dihydropyrido[3,2-b]thieno[2,3-d]oxepin-9-yl)-1-(2,4-differenl)-1,2,4-triazole;
2-(4-(2-chlorophenyl)-5-oxo-4,5-dihydro-1H-1,2,4-triazole-3-yl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-8-carboxamide;
N-(2-amino-ethyl)-2-(4-(2-chlorophenyl)-4H-1,2,4-triazole-3-yl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-8-carboxamide;
8-cyano-4,5-dihydro-6-oxa-1-Aza-3-thia-benzo[e]azulene-2-carboxylic acid (2-chloro-(4-methylcarbamoyl)phenyl)-methyl-amide;
N-(2-chloro-4-(methylcarbamoyl)phenyl)-9-cyano-N-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2-carboxamide;
8-methylcarbamoyl-4,5-dihydro-6-oxa-1-Aza-3-thia-benzo[e]azulene-2-carboxylic acid(2-chloro-(4-methylcarbamoyl)phenyl)-methyl-amide;
N2-(2-chlorophenyl)-N9-ethyl-N2-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2,9-dicarboxamide;
N-(2,4-dichlorophenyl)-N-methyl-9-(piperazine-1-carbonyl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-1-2-carboxamide;
N-(2-acetamidomethyl)-2-(4-(2-chlorophenyl)-4H-1,2,4-triazole-3-yl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-8-carboxamide;
2-(4-(2-chlorophenyl)-4H-1,2,4-triazole-3-yl)-N-(2-morpholinoethyl)-4,5-dihydrobenzo the[b]thieno[2,3-d]oxepin-8-carboxamide;
2-(4-(2-chlorophenyl)-4H-1,2,4-triazole-3-yl)-N-(2-(dimethylamino)ethyl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-8-carboxamide;
2-(4-(2-chlorophenyl)-4H-1,2,4-triazole-3-yl)-N-(1,3-dihydroxypropyl-2-yl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-8-carboxamide;
N2-(2-chloro-4-(methylcarbamoyl)phenyl)-N2-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2,9-dicarboxamide;
5-(8-(1H-pyrazole-4-yl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2-yl)-4-(2-chlorophenyl)-4H-1,2,4-triazole-3-amine;
5-(6,7-dihydropyrido[3,2-b]thieno[2,3-d]oxepin-9-yl)-2-acetaminophenodeine;
N-(2-chloro-4-(dimethylcarbamoyl)phenyl)-N-methyl-(3-hydroxymethyl-6,7-dihydropyrido[3,2-b]thieno[2,3-d]oxepin)-9-carboxamide;
N-(2-chlorophenyl)-N-methyl-8-(1H-pyrazole-5-yl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2-carboxamide;
2-(4-(2-chlorophenyl)-4H-1,2,4-triazole-3-yl)-N-((R)-2-hydroxypropyl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-8-carboxamide;
2-(4-(2-chlorophenyl)-4H-1,2,4-triazole-3-yl)-N-(2-hydroxyethyl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-8-carboxamide;
4-(2-chlorophenyl)-3-(4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2-yl)-4H-1,2,4-triazole;
8-bromo-2-[4-(2-chlorophenyl)-4H-[1,2,4]triazole-3-yl]-4,5-dihydro-6-oxa-3-thia-1-Aza-benzo[e]azulene;
N-(2-chlorophenyl)-N-methyl-(8-amino-4,5-dihydropyrido-[4,3-b]thieno[2,3-d]oxepin-2)-carboxamide;
N-(2-chlorophenyl)-N-methyl-(8-atsetamino-4,5-dihydropyrido-[4,3-b]thieno[2,3-d]oxepin-2)-carboxamide;
N-(2-chloro-4-(piperazine-1-carbonyl)phenyl)-N-(2-hydroxyethyl)-4,5-dihydrobenzo[b]thieno[2,3-d]oaks is in-2-carboxamide;
N-(2-chlorophenyl)-N-methyl-8-(3-methyl-1H-pyrazole-4-yl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2-carboxamide;
5-(6,7-dihydropyrido[3,2-b]thieno[2,3-d]oxepin-9-yl)pyridine-2-methylamine;
3-(4,5-dihydropyrido[4,3-b]thieno[2,3-d]oxepin-2-yl)-4-(2-chlorophenyl)-4H-1,2,4-triazole;
3-(4,5-dihydropyrido[4,3-b]thieno[2,3-d]oxepin-2-yl)-4-(2-chlorophenyl)-1H-1,2,4-triazole-5(4H)-she;
N-(4-carbarnoyl-2-chlorophenyl)-N-(2-hydroxyethyl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2-carboxamide;
N2-(2,4-dichlorophenyl)-N2,N8-dimethyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2,8-dicarboxamide;
4-(4,5-dihydropyrido[4,3-b]thieno[2,3-d]oxepin-2-yl)-5-(2-chlorophenyl)-2H-1,2,3-triazole;
2-(1-(2-chlorophenyl)-1H-1,2,4-triazole-5-yl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-8-carbonitrile;
4,5-dihydro-6-oxa-1-thia-3-Aza-benzo[e]azulene-2-carboxylic acid (2-chloro-phenyl)-methyl-amide;
N-(2-chlorophenyl)-N-methyl-4,5-dihydrobenzo[b]thieno[3,2-d]oxepin-2-carboxamide;
2-(1-(2,4-differenl)-1H-1,2,4-triazole-5-yl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-8-carboxamide;
2-(4-(2-chloro-4-(methylcarbamoyl)phenyl)-4H-1,2,4-triazole-3-yl)-N-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-8-carboxamide;
2-(4-(2-chlorophenyl)-5-oxo-4,5-dihydro-1H-1,2,4-triazole-3-yl)-N-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-8-carboxamide;
N-(2-acetamidomethyl)-2-(4-(2-chlorophenyl)-5-oxo-4,5-dihydro-1H-1,2,4-triazole-3-yl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-8-carboxamide;
N-(2-amino-2-methylpropyl)-2-(4-(2-chlorophenyl)-5-oxo-4,5-dihydr what-1H-1,2,4-triazole-3-yl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-8-carboxamide;
N8-(2-acetamidomethyl)-N2-(2-chloro-4-(dimethylcarbamoyl)phenyl)-N2-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2,8-dicarboxamide;
N2-(2-chloro-4-(dimethylcarbamoyl)phenyl)-N8-(2-(dimethylamino)ethyl)-N2-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2,8-dicarboxamide;
5-(6,7-dihydropyrido[3,2-b]thieno[2,3-d]oxepin-9-yl)Benzen-2-methylamine;
9-cyano-N-(2,4-dichlorophenyl)-N-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2-carboxamide;
3-(8-(pyrazole-4-yl)-4,5-dihydro-6-oxa-1-Aza-3-thia-benzo[e]azulene-2-yl)-4-(2-chlorophenyl)-4H-1,2,4-triazole;
N2-(2-chloro-4-(dimethylcarbamoyl)phenyl)-N8-(2-hydroxyethyl)-N2-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2,8-dicarboxamide;
N2-(2-chloro-4-(dimethylcarbamoyl)phenyl)-N8-isopropyl-N2-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2,8-dicarboxamide;
N8-(2-amino-2-methylpropyl)-N2-(2-chloro-4-(dimethylcarbamoyl)phenyl)-N2-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2,8-dicarboxamide;
2-(1-(2-chloro-4-(dimethylcarbamoyl)phenyl)-1H-1,2,4-triazole-5-yl)-N-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-8-carboxamide;
4-(5-(8-bromo-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2-yl)-1H-1,2,4-triazole-1-yl)-3-chloro-N,N-dimethylbenzamide;
N-(2-chloro-4-(dimethylcarbamoyl)phenyl)-9-cyano-N-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2-carboxamide;
2-(9-cyano-4,5-dihydro-6-oxa-1-Aza-3-thia-benzo[e]azulene)-N-(2-chloro-4-(methylcarbamoyl)phenyl)-N-methyl-carboxamide;
2-(1-isopropyl-1H-1,2,4-triazole-5-yl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-8-carboxamide;
N2-(2-chloro-4-(dimethylcarbamoyl)phenyl)-N8-isobutyl-N2-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2,8-dicarboxamide;
N2-(2-chloro-4-(dimethylcarbamoyl)phenyl)-N8-ethyl-N2-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2,8-dicarboxamide;
N2-(2-chloro-4-(dimethylcarbamoyl)phenyl)-N8-isobutyl-N2-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2,8-dicarboxamide;
5-(3-methylcarbamoyl-6,7-dihydropyrido[3,2-b]thieno[2,3-d]oxepin-9-yl)pyridine-2-amine;
4-(3-methylcarbamoyl-6,7-dihydropyrido[3,2-b]thieno[2,3-d]oxepin-9-yl)-5-(2-chlorophenyl)-2H-1,2,3-triazole;
N2-(2-chloro-4-(dimethylcarbamoyl)phenyl)-N2-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2,8-dicarboxamide;
N8-(2-amino-ethyl)-N2-(2-chloro-4-(dimethylcarbamoyl)phenyl)-N2-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2,8-dicarboxamide;
N-(2-chloro-4-(2-hydroxypropylamino)phenyl)-9-cyano-N-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2-carboxamide;
3-(9-bromo-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2-yl)-4-(2-chlorophenyl)-4H-1,2,4-triazole;
2-(4-(2-chloro-4-forfinal)-4H-1,2,4-triazole-3-yl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-9-carbonitrile;
9-bromo-N-(2,4-dichlorophenyl)-N-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2-carboxamide;
N-(2-chloro-4-cyanophenyl)-9-cyano-N-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2-carboxamide;
N-(2-chloro-4-(trifluoromethyl)phenyl)-9-cyano-N-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2-carboxamide;
N-(2,4-dichlorophenyl)-N-methyl-9-(4-methylpiperazin-1-carbonyl)-4,5-Digi is robinso[b]thieno[2,3-d]oxepin-2-carboxamide;
N-(2,4-dichlorophenyl)-9-((3S,5R) - for 3,5-dimethylpiperazine-1-carbonyl)-N-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2-carboxamide;
N2-(2,4-dichlorophenyl)-N9-(2-hydroxyethyl)-N2-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2,9-dicarboxamide;
N-(4-(dimethylcarbamoyl)phenyl)-N-methyl-(2-chloro-6,7-dihydropyrido[3,2-b]thieno[2,3-d]oxepin)-9-carboxamide;
2-(4-(2-chlorophenyl)-1-methyl-5-oxo-4,5-dihydro-1H-1,2,4-triazole-3-yl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-8-carboxamide and
2-(4-(2-chlorophenyl)-1-methyl-5-oxo-4,5-dihydro-1H-1,2,4-triazole-3-yl)-N-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-8-carboxamide.

15. The compound according to claim 1, selected from
2-(8-bromo-4,5-dihydro-6-oxa-1-Aza-3-thia-benzo[e]azulene)-N-(2,4-debtor)phenyl)-N-methyl-carboxamide;
3-(2-cyano-6,7-dihydropyrido[3,2-b]thieno[2,3-d]oxepin-9-yl)-2-(2,4-differenl)-2H-1,2,4-triazole;
4-(2-cyano-6,7-dihydropyrido[3,2-b]thieno[2,3-d]oxepin-9-yl)-5-(2,4-differenl)-2H-1,2,3-triazole;
3-(9-bromo-4,5-dihydro-6-oxa-1-Aza-3-thia-benzo[e]azulene-2-yl)-4-(2,4-differenl)-4H-1,2,4-triazole;
N2-(2-chloro-4-forfinal)-N2,N8-dimethyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2,8-dicarboxamide;
2-(1-(2-chloro-4-(dimethylcarbamoyl)phenyl)-1H-1,2,4-triazole-5-yl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-8-carboxamide;
2-(1-(2,4-differenl)-1H-1,2,4-triazole-5-yl)-1H-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-8-carboxamide;
N2-(2-chloro-4-(methylcarbamoyl)phenyl)-N2-(2-hydroxyethyl)-N8-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2,8-dicarboxamide;
3-(8-carbarnoyl-4,5-dihydro-6-oxa-1-Aza-3-thia-benzo[e]azulene-2-yl)-4-(2-forfinal)-4H-1,2,4-triazole;
(2-(4-(2,4-differenl)-4H-1,2,4-triazole-3-yl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-9-yl)(4-methylpiperazin-1-yl)methanone;
2-(4-(2,4-differenl)-4H-1,2,4-triazole-3-yl)-N-(2-hydroxyethyl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-9-carboxamide;
2-(4-(2,4-differenl)-4H-1,2,4-triazole-3-yl)-N-(2-hydroxyethyl)-N-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-9-carboxamide;
2-(1-(2,4-differenl)-1H-1,2,4-triazole-5-yl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-8-carbonitrile;
N-(4-(dimethylcarbamoyl)phenyl)-N-methyl-(2-cyano-6,7-dihydropyrido[3,2-b]thieno[2,3-d]oxepin)-9-carboxamide;
4-(2-carbarnoyl-6,7-dihydropyrido[3,2-b]thieno[2,3-d]oxepin-9-yl)-5-(2,4-differenl)-2H-1,2,3-triazole;
3-(8-cyano-4,5-dihydro-6-oxa-1-Aza-3-thia-benzo[e]azulene-2-yl)-4-(2,4-differenl)-4H-1,2,4-triazole;
3-(8-methylcarbamoyl-4,5-dihydro-6-oxa-1-Aza-3-thia-benzo[e]azulene-2-yl)-4-(2-forfinal)-4H-1,2,4-triazole;
2-(1-(2-hydroxyethyl)-1H-1,2,4-triazole-5-yl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-8-carboxamide;
3-(8-methylcarbamoyl-4,5-dihydro-6-oxa-1-Aza-3-thia-benzo[e]azulene-2-yl)-2-(2,5-differenl)-2H-1,2,4-triazole;
5-(9-bromo-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2-yl)-1-(2,4-differenl)-1H-1,2,4-triazole;
5-(9-bromo-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2-yl)-1-isopropyl-1H-1,2,4-triazole;
3-(8-methylcarbamoyl-4,5-dihydro-6-oxa-1-Aza-3-thia-benzo[e]azulene-2-yl)-2-(2-forfinal)-2H-PI is Azola;
N2-(2-chloro-4-forfinal)-N2-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2,8-dicarboxamide;
N2-(2-chloro-5-(dimethylcarbamoyl)phenyl)-N2-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2,8-dicarboxamide;
N2-(2-chloro-5-(dimethylcarbamoyl)phenyl)-N2,N8-dimethyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2,8-dicarboxamide;
2-(4-isopropyl-1-methyl-5-oxo-4,5-dihydro-1H-1,2,4-triazole-3-yl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-8-carboxamide;
3-(8-carbarnoyl-4,5-dihydro-6-oxa-1-Aza-3-thia-benzo[e]azulene-2-yl)-2-(2,4-differenl)-2H-1,2,4-triazole;
3-(2-carbarnoyl-6,7-dihydropyrido[3,2-b]thieno[2,3-d]oxepin-9-yl)-4-(2,4-differenl)-4H-1,2,4-triazole;
3-(2-cyano-6,7-dihydropyrido[3,2-b]thieno[2,3-d]oxepin-9-yl)-4-(2,4-differenl)-4H-1,2,4-triazole;
3-(8-carbarnoyl-4,5-dihydro-6-oxa-1-Aza-3-thia-benzo[e]azulene-2-yl)-2-(2,5-differenl)-2H-1,2,4-triazole;
5-(8-(1H-pyrazole-4-yl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2-yl)-1-isopropyl-1H-1,2,4-triazole;
3-(8-(1H-pyrazole-4-yl)-4,5-dihydro-6-oxa-1-Aza-3-thia-benzo[e]azulene-2-yl)-2-(2-forfinal)-2H-pyrazole;
1 -(2,4-differenl)-5-(4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2-yl)-1 H-1,2,4-triazole;
2-(1-(2,4-differenl)-1H-1,2,4-triazole-5-yl)-N-(2-hydroxyethyl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-9-carboxamide;
9-bromo-2-[2-(2,4-debtor-phenyl)-2H-[1,2,4]triazole-3-yl]-4,5-dihydro-6-oxa-3-thia-1-Aza-benzo[e]azulene;
5-(9-(1H-pyrazole-4-yl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2-yl)-1-(2,4-differenl)-1H-1,2,4-triazole;
2-(1-(2,4-difthe who yl)-1H-1,2,4-triazole-5-yl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-9-carboxamide;
(2-(1-(2,4-differenl)-1H-1,2,4-triazole-5-yl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-9-yl)(piperazine-1-yl)methanone;
4-(3-carbarnoyl-6,7-dihydropyrido[3,2-b]thieno[2,3-d]oxepin-9-yl)-5-(2,4-differenl)-2H-1,2,3-triazole;
8-(1H-pyrazole-4-yl)-4,5-dihydro-6-oxa-1-Aza-3-thia-benzo[e]azulene-2-carboxylic acid N-(2,4-differenl)-N-methyl-amide;
N2-(4-carbarnoyl-2-chlorophenyl)-N2,N8-dimethyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2,8-dicarboxamide;
2-(1-(2-chloro-5-(dimethylcarbamoyl)phenyl)-1H-1,2,4-triazole-5-yl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-8-carboxamide;
2-[4-(2,4-Debtor-phenyl)-4H-[1,2,4]triazole-3-yl]-4,5-dihydro-6-oxa-3-thia-1-Aza-benzo[e]azulene-9-carboxylic acid amide;
3-(2-(1-(2,4-differenl)-1H-1,2,4-triazole-5-yl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-9-yl)pyridine;
8-(1H-pyrazole-4-yl)-2-[2-(2,5-debtor-phenyl)-2H-[1,2,4]triazole-3-yl]-4,5-dihydro-6-oxa-3-thia-1-Aza-benzo[e]azulene;
8-(1H-pyrazole-4-yl)-2-[2-(2-fluoro-phenyl)-2H-[1,2,4]triazole-3-yl]-4,5-dihydro-6-oxa-3-thia-1-Aza-benzo[e]azulene;
5-(2-chloro-6,7-dihydropyrido[3,2-b]thieno[2,3-d]oxepin-9-yl)-4-(2,4-differenl)-1H-imidazole;
2-(1-(1,1,1-tryptophan-2-yl)-1H-1,2,4-triazole-5-yl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-8-carboxamide;
N2-(2-chloro-4-(4-methylpiperazin-1-carbonyl)phenyl)-N2-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2,8-dicarboxamide;
2-(5-cyclopropyl-[1,2,3]triazole-1-yl)-4,5-dihydro-6-oxa-3-thia-1-Aza-benzo[e]azulene-8-carboxylic acid amide;
2-(1-(2,4-differenl)-1H-1,2,-triazole-5-yl)-N-(2-hydroxyethyl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-8-carboxamide;
N-(2-acetamidomethyl)-2-(1-(2,4-differenl)-1H-1,2,4-triazole-5-yl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-8-carboxamide;
2-(1-(2,4-differenl)-1H-1,2,4-triazole-5-yl)-N-(2-(pyrrolidin-1-yl)ethyl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-8-carboxamide;
(2-(1-(2,4-differenl)-1H-1,2,4-triazole-5-yl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-9-yl)((R)-3-(dimethylamino)pyrrolidin-1-yl)methanone;
2-(1-isopropyl-1H-1,2,4-triazole-5-yl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-9-carboxamide;
(2-(1-(2,4-differenl)-1H-1,2,4-triazole-5-yl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-9-yl)((S)-3-(dimethylamino)pyrrolidin-1-yl)methanone;
5-(3-carbarnoyl-6,7-dihydropyrido[3,2-b]thieno[2,3-d]oxepin-9-yl)-1-(2,4-differenl)-1H-1,2,4-triazole;
2-(1-(2,2,2-triptorelin)-1H-1,2,4-triazole-5-yl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-8-carboxamide;
2-(2-carbarnoyl-6,7-dihydropyrido[3,2-b]thieno[2,3-d]oxepin-9-yl)-3-(2,4-differenl)-pyrazine;
5-(2-carbarnoyl-6,7-dihydropyrido[3,2-b]thieno[2,3-d]oxepin-9-yl)-4-(2,4-differenl)-1H-imidazole;
N2-(2-chloro-4-(piperazine-1-carbonyl)phenyl)-N2-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2,8-dicarboxamide;
N2-(4-(4-acetylpiperidine-1-carbonyl)-2-chlorophenyl)-N2,N8-dimethyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2,8-dicarboxamide;
2-[5-(2,4-Debtor-phenyl)-[1,2,3]triazole-1-yl]-4,5-dihydro-6-oxa-3-thia-1-Aza-benzo[e]azulene-8-carboxylic acid amide;
2-(1-isobutyl-1H-1,2,4-triazole-5-yl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-8-carboxamide;
9-bromo-2-isopropyl-2H-1,2,4-triazole-3-yl-4,5-dihydro-6-oxa-3-thia-1-Aza-benzo[e]azulene;
4-(2-carbarnoyl-6,7-dihydropyrido[3,2-b]thieno[2,3-d]oxepin-9-yl)-3-(2,4-differenl)-1,2,5-oxadiazole;
9-(1H-pyrazole-4-yl)-2-isopropyl-2H-1,2,4-triazole-3-yl-4,5-dihydro-6-oxa-3-thia-1-Aza-benzo[e]azulene;
5-(2-carbarnoyl-6,7-dihydropyrido[3,2-b]thieno[2,3-d]oxepin-9-yl)-1-(2,4-differenl)-1H-1,2,4-triazole;
(9-(1-(2,4-differenl)-1H-1,2,4-triazole-5-yl)-6,7-Dihydropyrido[3,2-b]thieno[2,3-d]oxepin-2-yl)(4-methylpiperazin-1-yl)methanone;
2-(5-tert-butyl-[1,2,3]triazole-1-yl)-4,5-dihydro-6-oxa-3-thia-1-Aza-benzo[e]azulene;
2-(5-tert-butyl-[1,2,3]triazole-1-yl)-4,5-dihydro-6-oxa-3-thia-1-Aza-benzo[e]azulene-8-carboxylic acid amide;
2-(5-Isopropyl-[1,2,3]triazole-1-yl)-4,5-dihydro-6-oxa-3-thia-1-Aza-benzo[e]azulene-8-carboxylic acid amide;
2-(1-(1,1,1-tryptophan-2-yl)-1H-1,2,4-triazole-5-yl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-8-carboxamide;
2-(1-(1,1,1-tryptophan-2-yl)-1H-1,2,4-triazole-5-yl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-8-carboxamide;
2-(1-(2-hydroxy-2-methylpropyl)-1H-1,2,4-triazole-5-yl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-8-carboxamide;
N2-(4-carbarnoyl-2-chlorophenyl)-N2-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2,8-dicarboxamide;
N2-(2-chloro-4-(2-hydroxypropylamino)phenyl)-N2,N8-dimethyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2,8-dicarboxamide;
N2-(2-chloro-4-(2-hydroxypropylamino)phenyl)-N2-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2,8-dicarboxamide;
2-(1-cyclobutyl-1H-1,2,4-triazole-5-yl)-4,5-dihydrobenzo[b]is ieno[2,3-d]oxepin-9-carboxamide;
2-(1-cyclobutyl-1H-1,2,4-triazole-5-yl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-8-carboxamide;
9-(1H-3,5-dimethylpyrazol-4-yl)-2-isopropyl-2H-1,2,4-triazole-3-yl-4,5-dihydro-6-oxa-3-thia-1-Aza-benzo[e]azulene;
(3-chloro-4-(5-(4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2-yl)-1H-1,2,4-triazole-1-yl)phenyl)(4-methylpiperazin-1-yl)methanone;
2-(1-(2-(dimethylamino)ethyl)-1H-1,2,4-triazole-5-yl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-8-carboxamide;
(2-(1-(2-hydroxy-2-methylpropyl)-1H-1,2,4-triazole-5-yl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-9-yl)(4-methylpiperazin-1-yl)methanone;
2-[5-(2,4-Debtor-phenyl)-[1,2,4]triazole-1-yl]-4,5-dihydro-6-oxa-3-thia-1-Aza-benzo[e]azulene-8-carboxylic acid amide;
N2-(2-chloro-4-(2-(dimethylamino)ethylcarbamate)phenyl)-N2,N8-dimethyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2,8-dicarboxamide;
N2-(2-chloro-4-(2-dimethylamino)ethylcarbamate)phenyl)-N2-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2,8-dicarboxamide;
5-(8-(4H-1,2,4-triazole-3-yl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2-yl)-1-isopropyl-1H-1,2,4-triazole;
2-(2-aminopyridine-4-yl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-8-carbonitrile;
5-(2-carbarnoyl-6,7-dihydropyrido[3,2-b]thieno[2,3-d]oxepin-9-yl)-6-(2,4-differenl)pyridine-2-amine;
8-(1H-pyrazole-4-yl)-(4H-4-isobutyl-1,2,4-triazole-5-yl)-4,5-dihydro-6-oxa-3-thia-1-Aza-benzo[e]azulene;
(2-(1-(2,4-differenl)-1H-1,2,4-triazole-5-yl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-9-yl)(4-methylpiperazin-1-yl)methanone;
(2-(1-(2-chlorophenyl)-1H-1,2,4-resol-5-yl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-9-yl)(4-methylpiperazin-1-yl)methanone;
2-(1-(3-methylbutane-2-yl)-1H-1,2,4-triazole-5-yl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-8-carboxamide;
2-(5-(2-(4-(2-chlorophenyl)-4H-1,2,4-triazole-3-yl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-8-yl)-1H-1,2,4-triazole-1-yl)-N,N-dimethylethanamine;
2-(5-(2-(4-(2-chlorophenyl)-4H-1,2,4-triazole-3-yl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-8-yl)-1H-1,2,4-triazole-1-yl)ethanol;
2-(1-(4-((1H-1,2,4-triazole-1-yl)methyl)phenyl)-1H-1,2,4-triazole-5-yl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-8-carboxamide;
(4-methylpiperazin-1-yl)(2-(1-(2,2,2-triptorelin)-1H-1,2,4-triazole-5-yl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-9-yl)methanone;
8-(1-Mei-2-yl)-(4H-4-isopropyl-1,2,4-triazole-5-yl)-4,5-dihydro-6-oxa-3-thia-1-Aza-benzo[e]azulene;
8-(1H-3,5-dimethylpyrazol-4-yl)-2-isopropyl-2H-1,2,4-triazole-3-yl-4,5-dihydro-6-oxa-3-thia-1-Aza-benzo[e]azulene;
8-(1H-pyrazole-4-yl)-2-isopropyl-2H-1,2,4-triazole-3-yl-4,5-dihydro-6-oxa-3-thia-1-Aza-benzo[e]azulene;
8-(1H-pyrazole-4-yl)-(4-(R-1-methylisobutyl-4H)-1,2,4-triazole-5-yl)-4,5-dihydro-6-oxa-3-thia-1-Aza-benzo[e]azulene;
8-(1H-pyrazole-4-yl)-(4-(S-1-methylisobutyl-4H)-1,2,4-triazole-5-yl)-4,5-dihydro-6-oxa-3-thia-1-Aza-benzo[e]azulene;
8-(1H-pyrazole-4-yl)-(4-(R-1-methylpropyl-4H)-1,2,4-triazole-5-yl)-4,5-dihydro-6-oxa-3-thia-1-Aza-benzo[e]azulene;
8-(1H-pyrazole-4-yl)-(4-(5-1-methylpropyl-4H)-1,2,4-triazole-5-yl)-4,5-dihydro-6-oxa-3-thia-1-Aza-benzo[e]azulene;
8-(1H-pyrazole-4-yl)-(2-triptorelin-2H-1,2,4-triazole-3-yl)-4,5-dihydro-6-oxa-3-thia-1-Aza-benzo[e]azulene;
5-(2-(1 which is 3.5-dimethylpyrazol-4-yl)-6,7-dihydropyrido[3,2-b]thieno[2,3-d]oxepin-9-yl)-1-(2,4-differenl)-1H-1,2,4-triazole;
5-(2-(1H-pyrazole-4-yl)-6,7-dihydropyrido[3,2-b]thieno[2,3-d]oxepin-9-yl)-1-(2,4-differenl)-1H-1,2,4-triazole;
5-(2-(2-methylpiperid-3-yl)-6,7-dihydropyrido[3,2-b]thieno[2,3-d]oxepin-9-yl)-1-(2,4-differenl)-1H-1,2,4-triazole;
5-(2-(N-2-(pyrrolidin-1-yl)ethylcarbamate)-6,7-dihydropyrido[3,2-b]thieno[2,3-d]oxepin-9-yl)-1-(2,4-differenl)-1H-1,2,4-triazole;
5-((2-N-benzylcarbamoyl)-6,7-dihydropyrido[3,2-b]thieno[2,3-d]oxepin-9-yl)-1-(2,4-differenl)-1H-1,2,4-triazole;
2-(1-(1,1,1-Cryptor-3-methylbutane-2-yl)-1H-1,2,4-triazole-5-yl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-8-carboxamide;
2-(5-Isopropyl-[1,2,4]triazole-1-yl)-4,5-dihydro-6-oxa-3-thia-1-Aza-benzo[e]azulene-8-carboxylic acid amide;
8-carbarnoyl-2-isopropyl-2H-1,2,4-triazole-3-yl-4,5-dihydro-6-oxa-3-thia-1-Aza-benzo[e]azulene;
2-(2-carbarnoyl-67-Dihydropyrido[3,2-b]thieno[2,3-d]oxepin-9-yl)-3-(2,4-differenl)-5-aminopyrazine;
9-(imidazo-2-yl)-2-isopropyl-2H-1,2,4-triazole-3-yl-4,5-dihydro-6-oxa-3-thia-1-Aza-benzo[e]azulene;
8-(1H-pyrazole-4-yl)-((1,1,1-tryptophan-2-yl)-2H-1,2,4-triazole-3-yl)-4,5-dihydro-6-oxa-3-thia-1-Aza-benzo[e]azulene;
8-(1H-5-methyl-pyrazole-4-yl)-2-isopropyl-2H-1,2,4-triazole-3-yl-4,5-dihydro-6-oxa-3-thia-1-Aza-benzo[e]azulene;
2-(5-isopropyl-[1,2,4]triazole-1-yl)-8-(1H-pyrazole-4-yl)-4,5-dihydro-6-oxa-3-thia-1-Aza-benzo[e]azulene;
8-(imidazo-2-yl)-2-isopropyl-2H-1,2,4-triazole-3-yl-4,5-dihydro-6-oxa-3-thia-1-Aza-benzo[e]azulene;
8-(2-amino-pyrid-5-yl)-2-isopropyl-2H-1,2,4-triazole-3-yl-4,5-Digi the ro-6-oxa-3-thia-1-Aza-benzo[e]azulene;
9-(carbarnoyl)-2-isopropyl-2H-1,2,4-triazole-3-yl-4,5-dihydro-6-oxa-3-thia-1-Aza-benzo[e]azulene;
8-(1H-pyrazole-4-yl)-(1-temporoparietal-1H-1,2,4-triazole-5-yl)-4,5-dihydro-6-oxa-3-thia-1-Aza-benzo[e]azulene;
2-(5-Isopropyl-[1,2,4]triazole-1-yl)-9-(1H-pyrazole-4-yl)-4,5-dihydro-6-oxa-3-thia-1-Aza-benzo[e]azulene;
2-(5-Isopropyl-[1,2,4]triazole-1-yl)-4,5-dihydro-6-oxa-3-thia-1-Aza-benzo[e]azulene-9-carboxylic acid amide;
8-(1H-pyrazole-4-yl)-(4-isopropyl-4H-1,2,4-triazole-5-yl)-4,5-dihydro-6-oxa-3-thia-1-Aza-benzo[e]azulene;
8-(methylcarbamate)-(1-isopropyl-1H-1,2,4-triazole-5-yl)-4,5-dihydro-6-oxa-3-thia-1-Aza-benzo[e]azulene;
9-(2-amino-pyrid-5-yl)-2-isopropyl-2H-1,2,4-triazole-3-yl-4,5-dihydro-6-oxa-3-thia-1-Aza-benzo[e]azulene;
8-(1H-pyrazole-5-yl)-2-isopropyl-2H-1,2,4-triazole-3-yl-4,5-dihydro-6-oxa-3-thia-1-Aza-benzo[e]azulene;
8-(carbarnoyl)-(2-triptorelin-2H-1,2,4-triazole-3-yl)-4,5-dihydro-6-oxa-3-thia-1-Aza-benzo[e]azulene;
9-(tetrazol-5-yl)-2-isopropyl-2H-1,2,4-triazole-3-yl-4,5-dihydro-6-oxa-3-thia-1-Aza-benzo[e]azulene;
8-(cyano)-(2-triptorelin-2H-5-amino-1,2,4-triazole-3-yl)-4,5-dihydro-6-oxa-3-thia-1-Aza-benzo[e]azulene;
2-(5-isopropyl-[1,2,4]triazole-1-yl)-4,5-dihydro-6-oxa-3-thia-1-Aza-benzo[e]azulene-8-carboxylic acid (2-hydroxy-ethyl)-amide;
2-(5-isopropyl-[1,2,4]triazole-1-yl)-4,5-dihydro-6-oxa-3-thia-1-Aza-benzo[e]azulene-9-carboxylic acid (2-hydroxy-ethyl)-amide;
8-(carbarnoyl)-((1,1,1-tryptophan-2-yl)-2H-1,2,4-triazole-3-yl)-4,-dihydro-6-oxa-3-thia-1-Aza-benzo[e]azulene;
8-(morpholinomethyl)-2-isopropyl-2H-1,2,4-triazole-3-yl-4,5-dihydro-6-oxa-3-thia-1-Aza-benzo[e]azulene;
8-(1H-pyrazole-4-yl)-(2-isopropyl-2H-5-amino-1,2,4-triazole-3-yl)-4,5-dihydro-6-oxa-3-thia-1-Aza-benzo[e]azulene;
2-(2-carbarnoyl-6,7-dihydropyrido[3,2-b]thieno[2,3-d]oxepin-9-yl)-5-aminopyrazine;
8-(aminomethyl)-2-isopropyl-2H-1,2,4-triazole-3-yl-4,5-dihydro-6-oxa-3-thia-1-Aza-benzo[e]azulene;
8-(6-methylpiperid-3-yl)-(2-triptorelin-2H-5-amino-1,2,4-triazole-3-yl)-4,5-dihydro-6-oxa-3-thia-1-Aza-benzo[e]azulene;
8-((2-methylsulfonylmethyl)-amide)-(4-isopropyl-4H-1,2,4-triazole-5-yl)-4,5-dihydro-6-oxa-3-thia-1-Aza-benzo[e]azulene;
8-(methylcarbamoyl)-(1-isopropyl-1H-1,2,4-triazole-5-yl)-4,5-dihydro-6-oxa-3-thia-1-Aza-benzo[e]azulene;
8-(2-aminopurin-5-yl)-(2-triptorelin-2H-5-amino-1,2,4-triazole-3-yl)-4,5-dihydro-6-oxa-3-thia-1-Aza-benzo[e]azulene;
8-(atsetamidometil)-2-isopropyl-2H-1,2,4-triazole-3-yl-4,5-dihydro-6-oxa-3-thia-1-Aza-benzo[e]azulene;
8-(tetrazol-5-yl)-2-isopropyl-2H-1,2,4-triazole-3-yl-4,5-dihydro-6-oxa-3-thia-1-Aza-benzo[e]azulene;
8-(formamidine)-2-isopropyl-2H-1,2,4-triazole-3-yl-4,5-dihydro-6-oxa-3-thia-1-Aza-benzo[e]azulene;
8-(methylformamidine)-2-isopropyl-2H-1,2,4-triazole-3-yl-4,5-dihydro-6-oxa-3-thia-1-Aza-benzo[e]azulene;
8-(carbarnoyl)-(2-isopropyl-2H-5-amino-1,2,4-triazole-3-yl)-4,5-dihydro-6-oxa-3-thia-1-Aza-benzo[e]azulene;
5-(2-(morpholine-4-yl)-6,7-dihydropyrido[3,2-b]thieno[2,3-d]oxepin-9-yl)-1-(2,4-differenl)-1H-1,2,4-t is iatola;
5-(2-(N-benzylamino)-6,7-dihydropyrido[3,2-b]thieno[2,3-d]oxepin-9-yl)-1-(2,4-differenl)-1H-1,2,4-triazole;
(2-isopropyl-2H-1,2,4-triazole-3-yl)-4,5-dihydro-6-oxa-3-thia-1-Aza-benzo[e]azulene;
(2-triptorelin-2H-5-amino-1,2,4-triazole-3-yl)-4,5-dihydro-6-oxa-3-thia-1-Aza-benzo[e]azulene;
8-(hydroxymethyl)-2-isopropyl-2H-1,2,4-triazole-3-yl-4,5-dihydro-6-oxa-3-thia-1-Aza-benzo[e]azulene;
8-(N-(pyrid-2-yl)formamidine)-2-isopropyl-2H-1,2,4-triazole-3-yl-4,5-dihydro-6-oxa-3-thia-1-Aza-benzo[e]azulene;
8-(N-2-(8-3-hydroxypyrrolidine-1-yl)ethylcarbamate)-(2-triptorelin-2H-1,2,4-triazole-3-yl)-4,5-dihydro-6-oxa-3-thia-1-Aza-benzo[e]azulene;
5-(2-carbarnoyl-6,7-dihydropyrido[3,2-b]thieno[2,3-d]oxepin-9-yl)-2-amino-6-ethylpyridine;
8-(methylcarbamoyl)-(2-triptorelin-2H-5-amino-1,2,4-triazole-3-yl)-4,5-dihydro-6-oxa-3-thia-1-Aza-benzo[e]azulene;
5-(8-bromo-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2-yl)-1-isopropyl-1H-1,2,4-triazole;
2-(1-isopropyl-1H-1,2,4-triazole-5-yl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-8-carbonitrile;
5-(2-(N-piperazinil)-6,7-dihydropyrido[3,2-b]thieno[2,3-d]oxepin-9-yl)-1-(2,4-differenl)-1H-1,2,4-triazole;
5-(2-(3R,5S-dimethylpiperazine-1-yl)-6,7-dihydropyrido[3,2-b]thieno[2,3-d]oxepin-9-yl)-1-(2,4-differenl)-1H-1,2,4-triazole;
5-((2-(4-dimethylamino)piperidine-1-yl)-6,7-dihydropyrido[3,2-b]thieno[2,3-d]oxepin-9-yl)-1-(2,4-differenl)-1H-1,2,4-triazole;
8-(3-(2-oxopyrrolidin-1-yl)propanimidamide)-(2-triptorelin-2H-1,2,4-triazole-3-yl)-4,5-dihydr the-6-oxa-3-thia-1-Aza-benzo[e]azulene;
8-(methylcarbamoyl)-(2-triptorelin-2H-1,2,4-triazole-3-yl)-4,5-dihydro-6-oxa-3-thia-1-Aza-benzo[e]azulene;
(2-(2-isopropyl-2H-1,2,4-triazole-3-yl)-4,5-dihydro-6-oxa-3-thia-1-Aza-benzo[e]azulene-9-yl)(4-isopropylpiperazine-1-yl)methanone;
9-((2-methylsulfonylmethyl)-amide)-(4-isopropyl-4H-1,2,4-triazole-5-yl)-4,5-dihydro-6-oxa-3-thia-1-Aza-benzo[e]azulene;
3-(9-bromo-4,5-dihydro-6-oxa-1-thia-benzo[e]azulene-2-yl)-4-(2,4-dichloro-phenyl)-4H-[1,2,4]triazole and
N-(2-amino-ethyl)-2-(4-(2-chlorophenyl)-5-oxo-4,5-dihydro-1H-1,2,4-triazole-3-yl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-8-carboxamide.

16. Pharmaceutical composition having PI3K inhibitory activity containing a compound according to claim 1 and a pharmaceutically acceptable carrier, a sliding agent, a diluent or excipient.

17. Method of preparation of a pharmaceutical composition, which comprises mixing the compound according to claim 1 with a pharmaceutically acceptable carrier.

18. The use of compounds according to claim 1 in the treatment of cancer.

19. The use of compounds according to claim 1 in the manufacture of medicaments for prophylactic or therapeutic treatment of cancer.

20. The compound according to claim 1 for use in the prophylactic or therapeutic treatment of cancer.

21. Method of inhibiting or modulating activity lietkynes, comprising contacting lietkynes with an effective inhibitory amount of a compound according to claim 1.

22. The method according to item 21, from which causesa fact, what lebedkina represents PI3K.

23. The method according to item 22, wherein the PI3K is RLF-subunit.

24. Set for treatment of PI3K-mediated condition, comprising:
a) a first pharmaceutical composition comprising a compound according to claim 1, and
b) instructions for use of the specified composition.

25. A compound selected from the group comprising (4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-2-yl)(3,4-dihydroquinoline-1(2H)-yl)methanon or a stereoisomer, geometric isomer, tautomer or pharmaceutically acceptable salt of 2-(1-(2-(trifluoromethyl)-1H-benzo[d]imidazol-5-yl)-1H-1,2,4-triazole-5-yl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-8-carboxamide or a stereoisomer, geometric isomer, tautomer or a pharmaceutically acceptable salt.



 

Same patents:

FIELD: biotechnologies.

SUBSTANCE: invention refers to new compounds represented with common formula (I) to its pharmaceutically acceptable salts that have inhibiting activity in relation to products of amyloid β-protein (Aβ42) or decomposition with ferment of beta-site of amyloid-β (BACE1) precursor. In general formula , circle A represents aryl chosen from phenyl, which can be replaced with substitutes with number of 1 to 3, which have been chosen from a group of substitutes α, 5-6-membered heteroalkyl with sulphur atom as heteroatom that can have 1 to 3 substitutes chosen from a group of substitutes α, or 9-10-membered benzo-condensed heterocyclic group having 2 atoms of oxygen in heterocyclic part of the above group, which can be replaced with substitutes with number of 1 to 3, which have been chosen from the group of substitutes α, L means ordinary bond, -NRLCO- (in which RL means hydrogen atom) or -NRLCO-C1-6alkyl (in which RL means hydrogen atom). Circle B represents 5-6-membered heteroaryl or saturated heterocyclic group with 1-3 heteroatoms in a cycle, which have been chosen from a group of hydrogen, oxygen or sulphur atoms, each of which can have 1 to 3 substitutes chosen from the group of substitutes α, or 9-10-membered benzo-condensed group having 2 oxygen atoms in heterocyclic part of the above group, X means methylene that can have 1 to 2 substitutes chosen from the group of substitutes α, Y means methylene that can have 1 to 2 substitutes chosen from the group of substitutes α, and Z means oxygen atom. The rest substitutes are specified in the claim.

EFFECT: compounds can be used for treatment of neurodegenerative diseases caused with Aβ presented with Alzheimer disease as a typical case.

9 cl, 13 dwg, 12 tbl, 88 ex

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of general formula (I) , where is a substituted 5-member heteroaryl ring selected from thienyl, thiazolyl, oxazolyl, pyrrolyl, imidazolyl or pyrazolyl, W is selected from a group comprising N and -C=; M is selected from a group comprising -C(O)N(R1)OR2, -CXCONR1R2 and -C(O)OR1, or M is -C1-C2alkyl-C(O)N(R1)OR2, wherein is , R1 and R2 are independently selected from a group comprising -H, C1-C3-alkyl, C6-aryl, and C1-C3-alkyl-C6-aryl; R is selected from a group comprising H, C1-C3alkyl, halogen, NR1R2, -OR1 and C6aryl; n is an integer from 0 to 1; L and Y are as indicated in the claim; and to compounds of formula (II) , where L2 is selected from a group comprising H, - C0-C3alkyl- C6aryl, -C0-C3alkyl-heteroaryl, where the heteroaryl is pyridyl; -C1-C6alkyl, Y and M are the same as for compounds of formula (I). The invention also relates to a pharmaceutical composition based on compounds (I) and (II), having inhibiting action on histone deacetylase (HDAC), a method of inhibiting and a method of treating a disease which is sensitive to the HDAC inhibitor.

EFFECT: compounds of formula I and II as histone deacetylase inhibitors.

18 cl, 18 dwg, 10 tbl, 19 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: there are described new benzodiazepine compounds of general formula , wherein each R1, R2, R3 and R4 independently represent hydrogen or alkyl, or R2 and R3 together represent lower alkylene; A1 is lower alkylene optionally substituted by hydroxy; and R5 is a fragment of formula , wherein each R6 and R7 independently represents hydrogen, lower alkyl, cycloalkyl, phenyl, furyl, thienyl, pyrazolyl, etc.; each XA and XB independently represents a bond, lower alkylene, -CO-, -SO2- etc., a pharmaceutical composition containing them, and using the above compound as the pharmaceutical composition or for preparing the same.

EFFECT: new compounds may be used for preventing and treating cardiac arrhythmia.

8 cl, 1047 ex, 78 tbl

Iap inhibitors // 2491276

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of formula: U1-M-U2, where U1 and U2 have general formula (I), where: G stands for: IVb IVd ive, and values M, X1, X2, R2, R3, R3', R4, R4', R5, R5', R6, R6', R7, Z7, Z2, Z3, Z4, Q2 are given in item 1 of the formula.

EFFECT: compounds can be applied for induction of apoptosis in cell.

37 cl, 13 dwg, 43 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: present invention refers to compounds of formula (I) or pharmaceutically acceptable salts thereof wherein A, R1, R2, R3 and m are specified in the patent claim. The present invention also refers to the number of specific compounds, and to a pharmaceutical composition containing the above compounds effective for inhibition of kinases, such as glycogen synthase kinase 3 (GSK-3), Rho kinase (ROCK), Janus kinase (JAK), AKT, PAK4, PLK, CK2, KDR, MK2, JNK1, aurora, pim 1 and nek 2.

EFFECT: preparing the specific compounds and pharmaceutical composition containing the above compounds effective for kinase inhibition.

18 cl, 393 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to compounds of formula (I) and salts thereof wherein R1 represents -A11-A12-; R2 represents tetrahydrofurylmethyl, tetrahydropyranylmethyl or tetrahydropyranyl; A11 represents a single bond, methylene or 3,2-ethylene; A12 represents C1-6 alkyl, C3-6 cycloalkyl or C3-6 cycloalkyl containing methyl; R3 represents methoxy, cyano, cyclobutyloxymethyl, methoxymethyl or ethoxymethyl; and R4 represents methoxy or chlorine. Also, the invention also refers to a pharmaceutical composition possessing corticotrophin-releasing factor (CRF) receptor antagonist activity, containing a compound of formula (I), to a therapeutic/preventive agent, and a method of treating the diseases specified in the patent claim.

EFFECT: there are presented the compounds of formula (I) as corticotropin-releasing factor (CRF) receptor antagonists.

20 cl, 2 dwg, 2 tbl, 51 ex

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of formula 1 , where X and T are N or C, Q is a (3-7)-member aromatic ring which contains 0-3 nitrogen atoms as ring members, and which is optionally benzo-condensed and is substituted with oxo; C1-C6-alkyl; halogen- C1-C6-alkyl; hydroxy-C1-C6-alkyl; C1-C6-alkoxy; C6-C10-aryl; or a (3-7)-member heteroaryl containing 1-3 oxygen atoms, P is C1-C6-alkyl, optionally substituted with a halogen, and R is a group selected from: (i) -C1-C6-alkyl-R1, (ii) -NR2R3, (iii) -O-R4, (iv) -S-R5, (v) -C (=O))-R6, (vi) optionally substituted (3-7)-member heteroaryl containing 1-4 heteroatoms selected from a nitrogen atom, an oxygen atom and a sulphur atom, (vi) optionally substituted (3-7)-member heteroatom containing 1-4 heteroatoms selected from a nitrogen atom, an oxygen atom and a sulphur atom, (vii) optionally substituted, saturated or partially unsaturated, separate or condensed (3-10)-member heterocyclic ring containing 1-4 heteroatoms selected from a nitrogen atom, an oxygen atom and a sulphur atom, (viii) azido; where each R1, R2, R3, R4, R3, R6, is as described in the claim. The invention also relates to a pharmaceutical composition for preventing and treating a vascular disease, which contains a compound of formula 1.

EFFECT: compounds of formula 1 with inhibitory activity with reference to aggregation of thrombocytes.

7 cl, 7 dwg, 2 tbl, 519 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a 2-aza-bicyclo[3.3.0]octane derivative of formula , with stereogenic centres in a (1S,3S,5S)-configuration, where A is a thiazolyl which is unsubstituted or monosubstituted, where the substitute is independently selected from a group comprising C1-4alkyl, C3-6cycloalkyl and NH2; B is phenyl which is unsubstituted or mono- or disubstituted, where the substitutes are independently selected from a group comprising C1-4alkyl, trifluoromethyl, NHC(O)CH3 and halogen; and R1 is an imidazo[2,1·b]thiazolyl or benzoisoxazolyl group, where said groups are independently unsubstituted or monosubstituted, where the substitutes are independently selected from a group comprising C1-4alkyl; or R1 is a 2,3-dihydrobenzofuranyl group; or a pharmaceutically acceptable salt. The 2-aza-bicyclo[3.3.0]octane derivative of formula (I) is as a medicinal agent having the activity of orexin receptor antagonists.

EFFECT: obtaining novel 2-aza-bicyclo[3,3,0]octane derivatives as orexin receptor antagonists.

8 cl, 1 tbl, 26 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to a compound of general formula:

or its pharmaceutically acceptable salt wherein the ring A represents a phenyl group which can contain 1-3 substitutes specified in a group of substitutes, or a thienyl group which can contain 1-3 substitutes specified in a group of substitutes α; L represents a single bond or a group of formula -NRC CO- (wherein Re represents a hydrogen atom), the ring B represents C6-14 aryl group which can contain 1-3 substitutes specified in a group of substitutes α, or a 5-10-member heterocyclic group which can contain 1-3 substitutes specified in a group of substitutes α; the X, Y, Z , R1 and R2 , R3, R4, R5 and R6 radical values are presented in cl.1 of the patent claim which possess an effect of Aβ protein production inhibition or an effect of BACE1 inhibition.

EFFECT: preparing the compound which is applicable as a preventive or therapeutic agent for neurodegenerative disease caused by Aβ.

13 cl, 35 tbl, 285 ex

FIELD: chemistry.

SUBSTANCE: invention relates to bicyclosulphonyl acid (BCSA) compounds of formula: where: where each of -Rpw, -Rpx, -RPY, and -RPZ independently denotes H or -RRS1; each -RRS1 independently denotes -F, -Cl, -Br, -I, -RA1, -CF3, -OH, -OCF3 or -ORA1; where each RA1 independently denotes C1-4alkyl, phenyl or benzyl; and additionally, two neighbouring -RRS1 groups can together form -OCH2O-, -OCH2CH2O- or -OCH2CH2CH2O-; -RAK independently denotes a covalent bond, -(CH2)- or -(CH2)2-; -RN independently denotes -RNNN, or -LN-RNNN; the rest of the values of the radicals are given in claim 1, which act as inhibitors of inhibitors of tumor necrosis factor-α converting enzyme (TACE).

EFFECT: compounds are useful in treating TNF-α mediated conditions.

36 cl, 303 ex

FIELD: biotechnologies.

SUBSTANCE: invention refers to compounds of formula I:

, where X means S or CR5;Y means S or CR7; where one of X or Y means S; each of R2, R5, R6 and R7 has been independently chosen from a group including the following: a) halogen; b) R8, -O-R8, -(C1-C6)alkylene-R8, -(C1-C6)alkylene-O-R8; where in each case R8 has been independently chosen from a group containing H, (C1-C6)alkyl, (C2-C6)alkenyl, (C3-C7)cycloalkyl and aryl; R3 means -W-R31 and bond is an ordinary bond; where W means O and R31 means (C1-C6)alkyl, (C3-C7)cycloalkyl, (C3-C7)cycloalkyl-(C1-C6)alkyl-; R4 means aryl or Het, where each aryl and Het optionally contains 1 to 5 substitutes, each of which has been independently chosen from a group containing halogen, (C1-C6)alkyl, (C2-C6)alkenyl, (C1-C6)haloalkyl, (C3-C7)cycloalkyl, (C3-C7)cycloalkyl-(C1-C6)alkyl-, -OH, -O(C1-C6)alkyl, -NH2, -NH(C1-C6)alkyl and -N((C1-C6)alkyl)2, which can be used for treatment of HIV infection.

EFFECT: improving compound application efficiency.

15 cl, 4 tbl, 55 ex

FIELD: chemistry.

SUBSTANCE: invention relates to dihydrothienopyrimidinesulphoxides of formula 1, and pharmaceutically acceptable salts thereof , where X denotes SO, R1 denotes H, R2 denotes H or a residue selected from C1-C10alkyl, which is optionally substituted with one or more residues selected from OR2.1, where R2.1 denotes H or C1-C6alkyl, R2.2 and R2.3 independently denote H or C1-C6alkyl, where Het is a 6-member monocyclic, saturated heterocycle containing 1 heteroatom selected from N or O, and where the hetaryl is a 5-11-member mono- or bicyclic, optionally anellated heteroaryl containing 1, 2 or 3 heteroatoms independently selected from N, S or O, and where the cycloalkyl can be saturated, or R2 denotes a monocyclic C3-cycloalkyl, which is optionally substituted with a residue selected from a branched or linear C1-C6alkanol, C1-C3alkylene-OR2.1, or R2 denotes phenyl which is optionally substituted with a halogen, or R2 denotes a residue selected from Het and hetaryl, each optionally substituted with one or more residues selected from halogen, OH, oxo group and OR2.1, C1-C6alkyl, and where R3 denotes a bicyclic 9-11-member unsaturated or partially saturated heterocycle which is optionally substituted with one or more residues selected from a group comprising F, O, Br, CF3, CN, OH, methyl, ethyl, propyl, isopropyl, -O-methyl, -O-ethyl, phenyl, NR2.2R2.3, where the phenyl is optionally substituted with F, Cl or Br. The invention also relates to pharmaceutical compositions based on said compounds, having phosphodiesterase 4 (PDE4) inhibiting activity.

EFFECT: obtaining novel compounds and pharmaceutical compositions based thereon, which can be used in medicine to treat respiratory or gastrointestinal complaints or diseases, inflammatory diseases of joints, skin or eyes, diseases of the peripheral or central nervous system or cancers.

20 cl, 1 tbl, 156 ex

FIELD: chemistry.

SUBSTANCE: invention relates to organic chemistry and specifically to compounds of the following formulae . The invention also relates to a pharmaceutical composition based on said compositions, having protein tyrosine kinase inhibiting activity.

EFFECT: novel compounds which can be used in medicine to treat ophthalmic diseases, disorders and pathological conditions.

11 cl, 7 tbl, 223 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: there are described new benzodiazepine compounds of general formula , wherein each R1, R2, R3 and R4 independently represent hydrogen or alkyl, or R2 and R3 together represent lower alkylene; A1 is lower alkylene optionally substituted by hydroxy; and R5 is a fragment of formula , wherein each R6 and R7 independently represents hydrogen, lower alkyl, cycloalkyl, phenyl, furyl, thienyl, pyrazolyl, etc.; each XA and XB independently represents a bond, lower alkylene, -CO-, -SO2- etc., a pharmaceutical composition containing them, and using the above compound as the pharmaceutical composition or for preparing the same.

EFFECT: new compounds may be used for preventing and treating cardiac arrhythmia.

8 cl, 1047 ex, 78 tbl

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to a compound of formula (I): and pharmaceutically acceptable salts, diastereoisomers and enantiomers thereof, wherein D is specified in a group consisting of , and , M is ; Z is -O-; Ar is a 6-member aromatic ring system substituted by 0 to 4 R2 groups; and G is or ; the other radical values are presented in cl.1 of the patent claim, as well as to using them for inhibiting protein tyrosine kinase inhibition.

EFFECT: preparing the new compounds.

14 cl, 33 tbl, 191 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to thienopyridazine compounds of formula (I) and to pharmaceutically acceptable salts and hydrates thereof, wherein R1 and R2 independently mean H or C1-4 alkyl; R3 means a saturated or unsaturated 5- or 6-members ring containing N, S or O, or optical isomers thereof, R4 means phenyl, monosubstituted or disubstituted halogen. The invention also refers to a method for preparing the above compounds and to a pharmaceutical composition for treating and preventing tumour diseases containing the above compounds.

EFFECT: there are prepared new compounds that may be used in medicine for treating anti-tumour diseases, particularly cancer.

12 cl, 3 tbl, 19 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: present invention refers to organic chemistry, namely azepine derivatives of general formula (I) or pharmaceutically acceptable salts thereof, wherein X represents S; R1 and R2 are independently specified in a group of substitutes consisting of H, halogen, C1-8-alkyl, C1-8-alkylphenyl, C2-8-alkenyl, OR5, CON(R5)2, SO2N(R5)2, phenyl, if necessary containing up to three substitutes of C1-4alkyl, halogen or C1-4alkoxy-groups; R3 is specified in a group consisting of H, C1-8-alkyl, OR5; R3a represents H, or R2 and R3 together represent a five-merous saturated cycle; R4 is specified in a group consisting of H, C1-8-alkyl; R4a represents H, or R4 and R4a together represent the substitute -CH2CH2-; R5 is specified in a group consisting of C1-8-alkyl, or R5 together with the atom whereto attached represents pyrrolidinyl; or R1 represents 4-trifluoromethoxyphenyl or 2-trifluoromethylphenyl, then X represents S, and R2, R3, R3a, R4 and R4a represents hydrogen, provided a derivative is other than 8- phenyl-5,6,7,8-tetrahydro-4H-thieno[2,3-d]azepin-3-ol and 2-bromo-8-phenyl-5,6,7,8-tetrahydro-4H-thieno[2,3-d]azepine-3-ol. Also, the invention refers to a pharmaceutical composition of the compounds of formula (I) and a method treating disorders on the basis of the use of the compound of formula (I).

EFFECT: there are produced new azepine derivatives effective in 5HT2C-receptor function modulation.

6 cl, 1 tbl, 49 ex

FIELD: medicine.

SUBSTANCE: invention describes crystals of 2-acetoxy-5-(α-cyclopropylcarbonyl-2-fluorobenzyl)-4,5,6,7-tetrahydrothieno[3,2-c]pyridine (prasugrel) hydrobromate, comprisions of crystals and pharmaceutical compositions containing them for preventing and treating the diseases associated with thrombus or embolism in an animal.

EFFECT: there are prepared new crystals of prasugrel hydrobromate which possess improved stability and solubility, and can find application in medicine.

13 cl, 7 dwg, 3 tbl, 11 ex

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of formula 1 , where X and T are N or C, Q is a (3-7)-member aromatic ring which contains 0-3 nitrogen atoms as ring members, and which is optionally benzo-condensed and is substituted with oxo; C1-C6-alkyl; halogen- C1-C6-alkyl; hydroxy-C1-C6-alkyl; C1-C6-alkoxy; C6-C10-aryl; or a (3-7)-member heteroaryl containing 1-3 oxygen atoms, P is C1-C6-alkyl, optionally substituted with a halogen, and R is a group selected from: (i) -C1-C6-alkyl-R1, (ii) -NR2R3, (iii) -O-R4, (iv) -S-R5, (v) -C (=O))-R6, (vi) optionally substituted (3-7)-member heteroaryl containing 1-4 heteroatoms selected from a nitrogen atom, an oxygen atom and a sulphur atom, (vi) optionally substituted (3-7)-member heteroatom containing 1-4 heteroatoms selected from a nitrogen atom, an oxygen atom and a sulphur atom, (vii) optionally substituted, saturated or partially unsaturated, separate or condensed (3-10)-member heterocyclic ring containing 1-4 heteroatoms selected from a nitrogen atom, an oxygen atom and a sulphur atom, (viii) azido; where each R1, R2, R3, R4, R3, R6, is as described in the claim. The invention also relates to a pharmaceutical composition for preventing and treating a vascular disease, which contains a compound of formula 1.

EFFECT: compounds of formula 1 with inhibitory activity with reference to aggregation of thrombocytes.

7 cl, 7 dwg, 2 tbl, 519 ex

FIELD: chemistry.

SUBSTANCE: compound is N-(4-{4-amino-7-[1-(2-hydroxyethyl)-1H-pyrazol-4-yl]thieno[3,2-c]pyridin-3-yl}phenyl-N'-(3-fluorophenyl)urea, N-(4-{4-amino-7-[1-(2-hydroxyethyl)-1H-pyrazol-4-yl]thieno[3,2-c]pyridin-3-yl}phenyl-N'-[4-(difluoromethoxy)phenyl]urea, N-[4-(4-amino-7-{l-[(2S)-2-hydroxypropyl)-1H-pyrazol-4-yl}thieno[3,2-c]pyridin-3-yl)phenyl]-N'-(3-methylphenyl)urea, N-(4- {4-amino-7-[1-(2-hydroxy-2-methylpropyl)-1H-pyrazol-4-yl]thieno[3,2-c]pyridin-3-yl}phenyl-N'-(4-methoxyphenyl)urea, N-[4-(4-amino-7-{1-[(2S)-2,3-dihydroxypropyl)-1H-pyrazol-4-yl}thieno[3,2-c]pyridin-3-yl)phenyl]-N'-(4-methoxyphenyl) or therapeutically acceptable salts thereof. A pharmaceutical composition based on said compounds is also disclosed.

EFFECT: obtaining novel compounds and a pharmaceutical composition based on said compounds, which can be used in medicine for treating cancer.

13 cl, 5 tbl, 6 ex

FIELD: chemistry.

SUBSTANCE: claimed invention relates to novel pyrimidine-substituted purine compound of formula (I) or pharmaceutically acceptable salt of said compound, which possess inhibiting action with respect to mTOR and P13 kinases and can be applied in cancer treatment. Formula (I) compound corresponds to structural formula Formula (I)

EFFECT: invention relates to pharmaceutical composition which contains therapeutically effective quantity of said compound and pharmaceutically acceptable diluents, auxiliary substance or carrier, to method of inhibition of proteinkinase, selected from mTOR or P13 kinase, and to method of treatment or prevention of state in mammal, associated with inhibition of mTOR and/or P13 kinase activity.

11 cl, 1 tbl, 3 ex

Up!