Intracellular calcium modulating compounds

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of formula (I): where: A, J, R1, R4, X, Z are given in claim 1, and to a pharmaceutical composition containing such compounds, which modulate activity of store-operated calcium (SOC) channels. The present invention also describes methods of using such SOC channel modulators to treat diseases or conditions where inhibition of activity of SOC channels can be beneficial.

EFFECT: improved method.

17 cl, 5 tbl, 2 dwg, 8 ex

 

The text descriptions are given in facsimile form.

1. The compound of formula (I):

where a represents a phenyl or benzofuran, each of which may substituted with at least one R;
R is selected from F, Cl, Br, I, -CN, -NO2, -CF3, -OH, -OR3, -OCF3With1-C6of alkyl, C3-C6cycloalkyl, C1-C6halogenoalkane and phenyl;
J is a bond;
R1is a CO2R2where R2represents hydrogen;
Z represents O, S or NH;
X is a W-L-B or, where possible, substituted with at least one R;
W represents NR2, Or Association;
L represents a methylene, ethylene, substituted with at least one R3-C6alkylen,2-C6albaniles or2-C6akinyan, where a methylene,3-C6alkylen,2-C6albaniles or2-C6akinyan possibly substituted by at least od what they R;
Selected from furan, thiophene, pyrrole, pyridine, oxazole, thiazole, imidazole, thiadiazole, benzoxazole, benzothiazole, benzimidazole, benzoxadiazole, benzothiadiazole, pyrazolopyrimidine, indolizine, properidine, thienothiophene, quinoline and isoquinoline;
each R3independently selected from C1-C6of alkyl;
each R4independently selected from hydrogen or C1-C6of alkyl; or its pharmaceutically acceptable salt, MES or N-oxide.

2. The compound according to claim 1, where R4represents hydrogen.

3. The compound according to claim 2, where Z represents O.

4. The compound according to claim 3, where a represents phenyl.

5. The compound according to claim 4, where phenyl is substituted by at least one R.

6. The compound according to claim 5, where phenyl is substituted by three R.

7. The connection according to claim 6, where R is selected from F, Cl, Br, I or C1-C6the alkyl.

8. The connection according to claim 7, where C1-C6alkyl represents methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl or tert-butyl.

9. The connection of claim 8, where X represents the Century

10. The connection according to claim 9, where selected from benzoxazole, benzothiazole, benzimidazole, pyrazolopyrimidine, benzoxadiazole and benzothiadiazole.

11. A compound selected from:
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and,
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and,
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and,
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,and
or its pharmaceutically acceptable salt or MES.

12. Pharmaceutical composition for the treatment of autoimmune diseases, heteromorpha disease or condition or inflammatory diseases containing a compound according to claim 1 and a pharmaceutically acceptable diluent, excipient, carrier or binder for them.

13. The use of compounds according to claim 1 or headlamp is asepticheski acceptable salts in the manufacture of a medicine for the treatment of autoimmune diseases, heteromorpha disease or condition, or inflammatory diseases.

14. Use item 13, where the autoimmune disease is a rheumatoid arthritis, multiple sclerosis, psoriasis, or osteoarthritis.

15. The application 14, where the autoimmune disease is a psoriasis.

16. Use item 13, where heteroman disease or condition is a graft rejection, or rejection of organ transplant.

17. Use item 13, where the inflammatory disease is a colitis.



 

Same patents:

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of formulae Ic-d , where X is O or S; R1 is selected from -(CR14R15)nNR12C(=Y)R10, -(CR14R15)nNR12S(O)2R10, -(CR14R15)nOR10, -C(=Y)NR10Rn, -C(-O)NR12(CR14R15)mNR10RH, -NHR12, C1-C12alkyl, C2-C8alkenyl, C3-C6heterocyclyl, which is a saturated carboxylic radical containing 3-6 ring atoms, wherein one ring atom is a heteroatom selected from nitrogen and oxygen, phenyl or a C4-C9heteroaryl, which is a univalent aromatic radical containing 1, 2 or 3 heteroatoms independently selected from nitrogen, oxygen and sulphur; R2 is selected from H, pyrimidinyl and C1-C6alkyl; mor is a morpholine group and R3 is a monocyclic heteroaryl group, and to pharmaceutically acceptable salts thereof.

EFFECT: compounds can be used to modulate lipid kinase activity, including PI3K, and to treat lipid kinase mediated disorders such as cancer.

15 cl, 2 tbl, 468 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a method of producing (S)-2-clopidogrel and salts thereof, which involves the following steps: (a) enzymatic hydrolysis of a racemic 2-chlorophenylglycine alkyl ester of formula 9 using an enzyme which is efficient for aqueous solution or aqueous phase hydrolysis to obtain an optically active compound of formula 10 ; (b) reaction of the formed optically active compound of formula 10 with a compound of formula 11 to obtain a compound of formula 12 and (c) cyclisation of the compound of formula 12 with a formulating agent in the presence of acid, where R1 denotes H, substituted or unsubstituted C1-C8-alkyl, substituted or unsubstituted C1-C8-alkenyl, benzyl or C3-C6-cycloalkyl; and X denotes a halogen atom selected from a group consisting of fluorine (F), chlorine (Cl), bromine (Br) and iodine (I), or -OSO2R2 (where R2 denotes a substituted or unsubstituted C1-C8-alkyl, substituted or unsubstituted aryl, substituted or unsubstituted arylalkyl, substituted or unsubstituted heteroaryl or substituted or unsubstituted heteroarylalkyl).

EFFECT: novel method of producing clopidogrel which does not involve use of chiral resolving agents, which reduces the cost of preparations while maintaining high output of the product.

7 cl, 4 ex

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of formula

where X is S or O, mor is a morpholine group, and R3 is a monocyclic heteroaryl group, including stereoisomers, geometric isomers, tautomers, solvates, metabolites and pharmaceutically acceptable salts thereof, which are used to modulate lipid kinase activity, including PI3K, and for treating lipid kinase mediated disorders such as cancer.

EFFECT: obtaining compounds which are used to modulate lipid kinase activity, including PI3K, and for treating lipid kinase mediated disorders such as cancer.

27 cl, 1 tbl, 354 ex

FIELD: chemistry.

SUBSTANCE: invention relates to substituted sulphamide derivatives of formula I: , in which n, m, R1, R2a-c, R3, R4, R5 and R6 are as described in claim 1, in form of a racemate, enantiomers, diastereomers, mixtures of enantiomers or diastereomers or a separate enantiomer or diastereomer, bases and/or salts of physiologically compatible acids. The invention also relates to a method of producing said compounds, a medicinal agent having antagonist action on bradykinin receptor 1 (B1R), containing such compounds, use of such compounds to produce medicinal agents, as well as sulphamide-substituted derivatives selected from a group of compounds given in claim 8.

EFFECT: providing novel compounds which are suitable as pharmacologically active substances in medicinal agents for treating disorders or diseases which are at least partially transmitted through B1R receptors.

13 cl, 581 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: there are produced new diazepane substituted compounds representing various heterocyclic systems, including condensed, pharmaceutical compositions containing said compounds.

EFFECT: producing the compounds and compositions for preventing and treating neurological and mental disorders and diseases with involved orexin receptors.

13 cl, 1 tbl

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of formula I , and pharmaceutically acceptable salts thereof, where L denotes O, S, or CH2; Y denotes N or CH; Z denotes CR3; G denotes CH; R1 denotes a heteroaryl ring of formula , where D1 denotes S, O; D2 denotes N or CR12; D3 denotes CR12; R2 denotes (C6-C10)-aryl; 5-9-member mono- or bicyclic heteroaryl with 1 or 2 heteroatoms independently selected from N or S; a saturated or partially saturated (C3-C7)-cycloalkyl; or a saturated 5-6-member heteocyclyl with 1 heteroatom selected from N, where said aryl, heteroaryl, cycloalkyl and heterocyclyl are optionally substituted with one or two groups independently selected from (C1-C6)-alkyl, F, Cl, Br, CF3, CN, NO2, OR6, C(-O)R6, C(=O)OR6, C(=O)NR6R7, saturated 6-member heterocyclyl with 2 heteroatoms independently selected from N or O, and S(O)2R6, and where said alkyl is optionally substituted with one -OR8 group; R3 denotes H; (C1-C6)-alkyl; (C2-C6)-alkenyl; Cl; Br; OR6; SR6; phenyl; or a 6-member heteroaryl with 1 heteroatom selected from N, where said alkyl and alkenyl are optionally substituted with one group selected from C(=O)OR8, -OR8, -NR8R9; or a saturated 6-member heterocyclyl with 1 heteroatom selected from N or O.

EFFECT: disclosed compounds are used in treating and preventing diseases mediated by insufficient level of glucokinase activity, such as sugar diabetes.

16 cl, 479 ex

FIELD: chemistry.

SUBSTANCE: invention relates to new compounds of indole with formula (I) or indole pharmaceutically acceptable salts: where: ring A stands for a benzene or a tiofen ring; R1 stands for a C1-.6 alkyl that may be substituted by one or several groups selected from among -OH, - O-C1-6 alkyl, an amino group that may be substituted by one or two C1-6 alkyls; -O-C1-6 alkyl; a halogen; CN; 5-6-membered cyclic amine; n is equal to 0 - 4 and to 0- 2 if ring A is a benzene or a tiofen ring accordingly; R2 stands for -H, -C1-6 alkyl; R3 stands for H, -C1-6 alkyl that may be substituted by phenyl, C3-6 cycloalkyl; R4 stands for C1-6 alkyl that may be substituted by one or several groups selected from among -OH, -O- C1-6 alkyl, an amino group that may be substituted by one or two C1-6 alkyls and 5-6-membered cyclic amine; C3-6 cycloalkyl, phenyl or-OH; X1 stands for -CH2-, -O-, -S-, -CH(R°)-; X2 stands for -C(RA)(RB)-, -O-; X3 stands for -C(RC)(RD)-; m is equal to 1 - 3; R° stands for -H, or R°, together with R4, form C3-6 alkylene; RA, RB, RC and RD are identical or different and stand for -H, C1-6 alkyl where, in case m is equal to 2 or 3, each RC and R° may be identical or different provided 1- methyl-4a-phenyl-2,3,4,4a,5,9b-hexahydro-1H-indeno [1,2-b] pyridine, 4a-phenyl-2,3,4,4a,5,9b-hexahydro-4aH-indeno [1,2-b] pyridine and 2-(1,2,3,4,5,9b-hexahydro-4aH-indeno [1,2-b] pyridine -4a-yl)-N,N-dimethylethanamine are excluded).

EFFECT: compounds possess antagonistic activity regarding NMDA receptor which enables their usage in pharmaceutical compositions for treatment of Alzheimer disease, vascular dementia, Parkinson disease, chronic depression, attention deficit hyperactivity disorder, migraines etc.

18 cl, 40 tbl, 84 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: claimed invention relates to compounds of formula (I) or to their pharmaceutically acceptable salts, in which X is selected from group, consisting of-C(R1)2-, -O-, -S-, -S(O2)-, -NR1-; each R1 is independently selected from group consisting of H and alkyl; each of R2, R3 and R4 is independently selected from group consisting of (1) H, (2) alkyl, (3) -OR5, (4) alkylene-OR5, (5) -alkylene-R6, (6) -C(O)O-alkyl, (7) - alkylene-C(O)O-alkyl, (8) -alkylene-R8, (9) -NHR5, (10) -N(R5)2, (11) alkenyl, (12) -NH-R8, (13) -NH-CH(C(O)O(C1-C6)alkyl)-alkylene-O-alkyleneR6, (14)-NHCH(C(O)O(C1-C6)aalkyl)-alkylene-OH, (15) -NH-C(O)-alkenyl and (16) -N(C1-C6alkyl)C(O)-alkenyl; or R2 and R3 or R2 and R4 or R3 and R4 together with atoms with which they are bound, form condensed 3-7-member cycloalkyl or heterocycloalkyl ring, which represents non-aromatic monocyclic ring system, which contains in ring from about 5 to about 7 atoms, and one or several atoms in ring system represent atom of element, different from carbon, for instance, nitrogen or oxygen, and said condensed cycloalkyl or heterocycloalkyl ring is not substituted or is substituted with one or several groups L3 ; and on condition that if X represents -O-, and m equals 1, then, at least, one of R2, R3 or R4 is not H; each R5 is independently selected from group consisting of (1) H, (2) (C1-C6)alkyl, (3) hydroxy-substituted alkyl, (4) R6, (5) R7, (6) -C(O)-(C1-C6)alkyl, (7) -C(O)-(C1-C6)halogenalkyl, (8) -C(O)-R6, (9) -C(O)-R7, (10) -C(O)NH-(C1-C6)alkyl, (11) -C(O)N((C1-C6)alkyl)2, in which each alkyl group is selected independently, (12) -S(O)2-(C1-C6)alkyl, (13) -S(O)2-(C1-C6)halogenalkyl, (14) -S(O)2-R6, (15) -S(O)2-R7, (16) -S(O)2-R8, (17) -alkylene-C(O)-(C1-C6)alkyl, (18) -alkylene-C(O)-(C1-C6)halogen-alkyl, (19) -alkylene-C(O)-R6, (20) -alkylene-C(O)-R7, (21) -alkylene-S(O)2-(C1-C6)alkyl, (22) -alkylene-S(O)2-(C1-C6)halogenalkyl, (23) -alkylene-S(O)2-R6, (24) -alkylene-S(O)2-R7, (25) -alkylene-S(O)2-R8, (26) -alkylene-NHC(O)-(C1-C6)alkyl, (27) -alkylene-NHC(O)-(C1-C6)halogenalkyl, (28) alkylene-NHC(O)-R6, (29) -alkylene-NHC(O)-R7, (30) -alkylene-NHS(O)2-(C1-C6)alkyl, (31) -alkylene-NHS(O)2-(C1-C6)halogenalkyl, (32) -alkylene-NHS(O)2-R6, (33) -alkylene-NHS(O)2-R7, (34) -alkylene-N(alkyl)C(O)-(C1-C6)alkyl, (35) -alkylene-N(alkyl)C(O)-(C1-C6)halogenalkyl, (36) -alkylene-N(alkyl)C(O)-R6, (37) -alkylene-N(alkyl)C(O)-R7, (38) -alkylene-N(alkyl)S(O)2-(C1-Ce)alkyl, (39) -alkylene-N(alkyl)S(O)2-(C1-C6)halogen-alkyl, (40)-alkylene-N(alkyl)S(O)2-R6, (41) -alkylene-N(alkyl)S(O)2-R7, (42) -alkylene-C(O)-NH-(C1-C6)alkyl, (43) -alkylene-C(O)-NHR6, (44) -alkylene-C(O)-NHR7, (45) -alkylene-S(O)2NH-(C1-C6)alkyl, (46) -alkylene-S(O)2NH-R6, (47) -alkylene-S(O)2NH-R7 , (48) -alkylene-C(O)-N((C1-C6)alkyl)2, in which each alkyl group is selected independently, (49) -alkylene-C(O)-N(alkyl)-R6, (50) -alkylene-C(O)-N(alkylene)-R7, (51) -alkylene-S(O)2N((C1-C6)alkyl)2, in which each alkyl group is selected independently, (52) -alkylene-S(O)2N(alkyl)-R6, (53) -alkylene-S(O)2N(alkyl)-R7, (54) -alkylene-OH, (55) -alkylene-OC(O)-NH-alkyl, (56) -alkylene-OC(O)NH-R8, (57) -alkylene-CN, (58) -R8, (59) -alkylene-SH, (60) -alkylene-S(O)2-NH-R8, (61) -alkylene-S(O)2-alkylene-R6, (62) substituted with halogen alkylene, (63) -C(O)OR8, (64) -C(O)O(C1-C6)alkyl, (65) -C(O)R8, (66) -C(O)-alkylene-O-(C1-C6)alkyl, (67) -C(O)NH2, (68) -alkylene-O-(C1-C6)alkyl, (69) -alkylene-R8, (70) -S(O)2-halogen(C1-C6)alkyl, (71) hydroxy-substituted halogen(C1-C6)alkyl, (72) -alkylene-NH2, (73) -alkylene-NH-S(O)2-R8, (74) -alkylene-NH-C(O)-R8, (75) -alkylene-NH-C(O)O-(C1-C6)alkyl, (76) -alkylene-O-C(O)-(C1-C6)alkyl, (77) -alkylene-O-S(O)2-(C1-C6)alkyl, (78) -alkylene-R6 , (79) -alkylene-R7, (80) -alkylene-NH-C(O)NH-(C1-C6)alkyl, (81) -alkylene-N(S(O)2 halogen(C1-C6)alkyl)2, and each -S(O)2 halogen(C1-C6)alkyl fragment is selected independently, (82) -alkylene-N((C1-C6)alkyl)S(O)2-R8 , (83) -alkylene-OC(O)-N(alkyl)2, and each alkyl is selected independently, (84) -alkylene-NH-(C1-C6)alkyl, (85) -C(O)-alkylene-C(O)O-(C1-C6)alkyl, (86) -C(O)-C(O)-O-(C1-C6)alkyl, (87) -C(O)-alkylene-R6, (88) -C(O)-NH-R8, (89) -C(O)-NH-R6, (90) -C(O)-NH-alkylene-R6, (91) -C(O)-alkylene-NH-S(O)2-halogen(C1-C6)alkyl, (92) -C(O)-alkylene-NH-C(O)-O-(C1-C6)alkyl, (93) -C(O)-alkylene-NH2, (94) -C(O)-alkylene-NH-S(O)2-R8, (95) -C(O)-alkylene-NH-S(O)2-(C1-C6)alkyl, (96) -C(O)-alkylene-NH-C(O)-(C1-C6)alkyl, (97) -C(O)-alkylene-N(S(O)2(C1-C6)alkyl)2, and each -S(O)2(C1-C6)alkyl fragment is elected independently, (98) -C(O)-alkylene-NH-C(O)-NH-(C1-C6)alkyl, (99) -alkylene-O-R6, (100) -alkylene-R7, (101) -C(O)OH, (102) -alkylene-N(S(O)2(C1-C6)alkyl)2, (103) -alkylene-C(O)-O-(C1-C6)alkyl, (104) halogenalkyl, (105) halogen, (106) -alkylene-C(O)-NH2, (107) =N-O-(C1-C6)alkyl, (108) =N-O-alkylene-R6, (109) =N-O-alkenyl, (110) -N-O-R6, (111) =N-NH-S(O)2-R6, (112) alkenyl, (113) =R8, (114) -O-C(O)-R9, (115) -O-C(O)-(C1-C6)alkyl, (116)-CN, R6 is selected from group consisting of unsubstituted (C6-C14)aryl, (C6-C14)aryl, substituted with one or several groups L1, unsubstituted (C5-C14)heteroaryl and (C5-C14)heteroaryl, which represents aromatic monocyclic or bicyclic system, which contains in ring from about 5 to about 9 atoms, and one or several atoms in ring system represent atom of element, different from carbon, for instance, nitrogen, oxygen or sulphur, one or in combination, substituted with one or several groups L1; R7 is selected from group consisting of unsubstituted heterocycloalkyl and heterocycloalkyl which represents non-aromatic monocyclic system, which contains in ring from about 4 to about 6 atoms, and one or several atoms in ring system represent atom of element, different from carbon, for instance, nitrogen, oxygen substituted with one or several groups L2; R8 is selected from group consisting of unsubstituted cycloalkyl and cycloalkyl substituted with one or several groups L2; A8 is selected from group consisting of (a) unsubstituted aryl, (b) aryl substituted with one or several groups L1; each group L1 is independently selected fron group consisting of halogen, alkyl, -CN, -CF3, -O-(C1-C6)alkyl, -O-(halogen(C1-C6)alkyl), -alkylen-OH (-CH2OH); each group L2 is independently selected from group consisting of (a) -OH, (b) alkyl, (c) alkyl substituted with one or several groups -OH and (d) piperidyl; each group L3 is independently selected from group consisting of -CN, =O, R5 , -OR5 ; =N-R5 and -N(R5)2; n equals 0, 1, 2 or 3; and m equals 0, 1 or 2; and on condition that in composition of substituent -OR5 fragment R5 and oxygen atom, which it is bound with, do not form group -O-O-; and on condition that in composition of substituents -OR5, =N-R5 and -NHR5 R5 are not -CH2OH, -CH2NH2, -CH2NH-alkyl, -CH2NH-aryl or -C(O)OH. Invention also relates to pharmaceutical composition, as well as to application of one or several compounds by one of ii. 1-125.

EFFECT: obtaining novel biologically active compounds possessing properties of γ-secretase inhibitor.

127 cl, 447 ex, 94 tbl

FIELD: chemistry.

SUBSTANCE: invention relates to azabenzothiophenyl compounds of formula I

and salts thereof, where: Z1 denotes CR1; Z2 denotes N; Z3 denotes CR3; Z4 denotes CR4; R1, R3 and R4 are independently selected from H or halogen; W denotes , R5 and R6 denote H; X1 denotes -OR11; X2 denotes phenyl which is optionally substituted with one or two groups selected from halogen or (C1-C3)alkylsulphanyl; R11 denotes (C1-C12) alkyl, substituted by one or two groups independently selected from - (CR19R20)nOR16; n equals 0; R16 denotes H, (C1-C12) alkyl or (C2-C8) alkenyl. The invention also relates to a pharmaceutical composition based on said compounds, which can be used in medicine for treating hyperproliferative disorders.

EFFECT: high efficiency of using said compounds.

11 cl, 12 ex

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of formulae

and ,

which can be used to inhibit lipid kinase, including PI3K, and treat lipid kinase-mediated disorders. Values of radicals are given in claim 1.

EFFECT: improved properties of the compound.

11 cl, 2 tbl, 7 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a compound of formula (I) , where Ar denotes each of R2, R3, R4, R5, R4' and R5' denote hydrogen; A denotes C(O); D denotes oxygen or NR8; E denotes CR63R64CR65R66; R63 and R64 denote hydrogen; R65 and R66 independently denote hydrogen or C1-4alkyl; k equals 0; m equals 1; R6 denotes a group -(X)p-Y-(Z)q-R10, or R6 denotes α- or β-branched C3-6alkyl (optionally substituted with C6cycloalkyl); X and Z independently denotes a C1-4alkylene group; p and q are independently equal to 0 or 1; Y denotes a bond; R8 denotes hydrogen; R10 denotes hydrogen or a saturated 5-7-member ring system; R7 denotes a 6-member aromatic ring, optionally substituted with a halogen, carboxyl, C1-6alkyl, C1-2alkoxy or a 5-member heteroaromatic ring (which is optionally substituted with C1-6alkyl); or a pharmaceutically acceptable salt thereof. Compounds of formula (I) or a pharmaceutically acceptable salt thereof are used to produce a medicinal agent for treating respiratory distress syndrome (ARDS), pulmonary emphysema, bronchitis, bronchiectasis, chronic obstructive pulmonary disease (COPD), asthma or rhinitis.

EFFECT: high efficiency of using said compounds.

7 cl, 1 tbl, 102 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to formula 1 compounds, possessing properties of Xa factor inhibitors, their pharmaceutically acceptable salts and based on them pharmaceutical compositions. In formula 1 cycle A stands for residue, selected from group, including the following structures: R1-R12 independently represents H, (C1-C7)alkyl or (C3-C7)cycloalkyl, R3 and R4 form cycle by binding (C3-C5)alkylene, alkylene carbon atom can be substituted with carbonyl; R13 stands for H, (C1-C7)alkyl or formyl.

EFFECT: obtaining compounds, possessing properties of Xa factor inhibitors.

8 cl, 5 ex, 3 tbl, 22 ex

FIELD: medicine.

SUBSTANCE: described are novel heterocyclic compounds of general formulae and (values of radicals are given in invention formula), pharmaceutical compositions containing them and application of said heterocyclic compounds for treatment disorders mediated with MAP kinase cascade.

EFFECT: increase of compound efficiency.

67 cl, 106 ex, 2 tbl, 2 dwg

FIELD: medicine.

SUBSTANCE: in claimed invention described is compound of general formula 1, or its pharmaceutically acceptable salt, where in each case independently on each other m equals 0, 1; p equals 1 or 2; R1 is selected from group, including -OH, -OC(O)NHMe, -OC(O)NMe2, -OC(O)NH(CH2)2Ph and OC(O)NH(CH2)2NMe2; R2 stands for -OH, -OC(O)Me, -OCH2CO2H, -OCH2CO2Et, -N3, -N=C(NMe2)2, -NH2, -NMe2, -NHC(O)Me, -NHC(O)CF3, - NHC(O)Ph, -NHC(O)NHPh, -NHC(O)CH2CH2CO2H, -NHC(O)CH2CH2CO2Me, - NHCH2Ph, -NHCH2(4-pyridyl), -NHCH2(2-pyridyl), -NHCH2(4-(CO2H)Ph), - NHCH2(3-(CO2H)Ph), -NHEt, -NHCHMe2, -NHCH2CHMe2, -N(CH2CHMe2)2, - NHCH2(cyclopropyl) or -NHC(O)CH2CH2NMe2; R3 stands for -OMe, -OEt, - OCH2(cyclopropyl), F, -O(CH2)2NMe2 or -O(CH2)2(4-morpholino); R4 stands for -NMe2, -NEt2, -NHEt, -NHCH2CHMe2, -N(Me)CH2CHMe2, - N(Me)CH2CH2NHS(O)2Me, -N(Me)CH2CH2NHS(O)2CF3, -NHCH2CH2OH, - N(Me)CH2CH2OH, -N(Me)CH2CO2H, -N(Me)CH2C(O)NH2, N(Me)CH2C(O)NHMe, -N(Me)CH2C(O)NMe2, -NHC(O)Me, 1-piperidinyl, 4-morpholino, (R)-2-(hydroxymethyl)-1-pyrrolidinyl, -NH2, -NO2, Br, CI, F, -C(O)Me or -CH2NH2; R5 stands for -OH or -N(R17)(R18); R17 and R18 independently in each case stand for H, (C1-C6)-alkyl, (C5-C7)-aryl-(C1-C6)-alkyl, where said aryl contains from zero to two heteroatoms, (C1-C6)-alkoxy or -[C(R19)(R20)]P-R21 R19 and R20 independently in each case represent H, (C1-C6)-alkyl, (C1-C6)-alkoxy, amino-(C1-C6)-alkyl, acylamino, sulfonylamino, (C5-C7)-aryl, (C5-C7)-aryl-(C1-C6)-alkyl or 3-10-membered heterocyclyl-(C1-C6)-alkyl, containing in ring from one to two heteroatoms; R21 independently in each case represents H, 3-10-membered heterocyclyl, containing in ring one heteroatom, (C1-C6)-alkylsulfonyl, (C1-C6)-alkylsulfonamido or amido; R22 stands for halogen; R23 stands for methyl; R24 stands for methyl and R25 stands for methyl, where said aryl stands for 5-7-membered ring, containing from zero to two heteroatoms, and said aryl or said heterocyclyl can be non-substituted or substituted halogen, (C1-C6)-alkyl or amino. Also described is pharmaceutical composition, possessing inhibiting activity with respect to Bcl-2 and/or Bcl-XL proteins, which includes said compound, also described is method of treating disorder, mediated by Bcl-2 and/or Bcl-XL proteins, which lies in introduction of said compound to patient, who needs such treatment, in therapeutically efficient amount.

EFFECT: increased efficiency of compound application.

41 cl, 6 dwg, 125 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a quinazoline derivative of general formula [1], or a pharmaceutically acceptable salt thereof [1], where R1-R6 assume values given claim 1, except compounds in which R5 is hydrogen and R6 is -NH2. The invention also relates to a pharmaceutical composition having the activity of an antipruritic agent, containing as an active ingredient said quinazoline derivative or pharmaceutically acceptable salt thereof.

EFFECT: obtaining a novel quinazoline derivative with low irritant action on skin and excellent action of significant suppression of scratching behaviour, as well as an antipruritic agent containing such a quinazoline derivative as an active ingredient.

9 cl, 250 ex, 7 tbl

FIELD: chemistry.

SUBSTANCE: invention relates to novel substituted pyrimidine derivatives having PGDS inhibiting properties. In formula (I): (I), R1 denotes phenyl or a 5- or 6-member heteroaryl containing 1-3 heteroatoms selected from N, O and S, each optionally having one or more of the following independent substitutes: halogen, (C1-C6)-alkyl, or (C1-C4)-haloalkyl; R2 denotes hydrogen or (C1-C6)-alkyl, which is optionally substituted with one or more halogens; R3 denotes hydrogen, (C1-C6)-alkyl or phenyl; R4 denotes C6-cycloalkyl, phenyl, a 6-member heterocyclyl containing one N heteroatom, a 6-member heteroaryl containing one N heteroatom, -C(=O)-NY1Y2, -C(=S)-NY1Y2, or -C(=O)-R5, where the phenyl, 6-member heteroaryl or 6-member heterocyclyl group optionally has one or more independent substitutes R6, or R3 and R4 together with a nitrogen atom with which they are bonded form a 5- or 6-member heterocyclyl containing one or two heteroatoms selected from N, O and S, a 6-member heterocyclenyl containing two or three N heteroatoms, a 5-member monocyclic or 9-member bicyclic heteroaryl containing one to three N heteroatoms, phenylheterocyclyl, where the heterocyclyl is 5- or 6-membered and contains one or two heteroatoms selected from N and O, each optionally having one or more independent substitutes R6. Values of R5, R6, Y1, Y2 are given in the claim. The invention also relates to a pharmaceutical composition containing said compounds.

EFFECT: improved method.

15 cl, 227 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to di(arylamino)aryl derivatives presented in the patent claim. The compounds show an inhibitory effect on protein EML4-ALK v1 and protein EGFR kinase activity. Also the invention refers to a pharmaceutical composition containing said compounds, the hybrid protein EML4-ALK and mutant protein EGFR kinase activity inhibitor, the use of said compounds for preparing the pharmaceutical composition, and to a method of preventing or treating non-small-cell lung cancer or EML4-ALK hybrid polynucleotide-positive and/or mutant EGFR polynucleotide-positive non-small-cell lung cancer.

EFFECT: use of di(arylamino)aryl as the protein EML4-ALK v1 and protein EGFR kinase activity inhibitors.

12 cl, 95 tbl, 55 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: it has been confirmed that the new azolcarboxamide compound or its pharmaceutically acceptable salt wherein a thiazole ring or an oxazole ring is bound to a benzene ring, a pyridine ring, a pyridazine ring, a thiophen ring, a pyrazole ring or a pyrrol ring through carboxamide or its ring possess high activity of receptor trkA inhibition; it has been found that they may be used as a therapeutic and/or preventive agent which is different in the fact concerning the effectiveness and safety for repeated urination, frequent micturate urge and urine incontinence associated with various urogenital diseases, including higher bladder activity, various lower bladder diseases accompanied with urogenital pain, such as interstitial cystitis, chronic prostatitis and others, and various diseases accompanied by pain; thereby the present invention has been created.

EFFECT: provided therapeutic and/or preventive agent for repeated urination, frequent micturate urge and urine incontinence associated with various urogenital diseases, including higher bladder activity, various lower bladder diseases accompanied with urogenital pain, such as interstitial cystitis, chronic prostatitis and others, and various diseases accompanied by pain on the basis of excellent inhibitory action on the receptor trkA.

24 cl, 1195 ex, 215 tbl

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of general formula (1), where R1 denotes a C1-C4 halogenalkyl group, R2 denotes a halogen atom, R3 denotes a C1-C6alkyl group, C1-C6alkoxy group or a halogen atom, m equals an integer from 0 to 5, n equals an integer from 0 to 4, M denotes an oxygen or sulphur atom, R4 is as defined in the claim. The invention also relates to a insect control method, use of compounds of formula (1) and a composition containing compounds of formula (1) for insect control.

EFFECT: obtaining compounds of formula (1) for insect control.

20 cl, 119 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a novel xinafoate salt of N4-[(2,2-difluoro-4H-benzo[1,4]oxazin-3-on)-6-yl]-5-fluoro-N2-[3-(methylaminocarbonyl methyleneoxy)phenyl]-2,4-pyrimidine diamine, having the structural formula given below. The invention also relates to a method of producing a salt, use of the latter, a pharmaceutical composition and a treatment method. The method of producing a xinafoate salt involves dissolving N4-[(2,2-difluoro-4H-benzo[1,4]oxazin-3-on)-6-yl]-5-fluoro-N2-[3-(methylaminocarbonyl methyleneoxy)phenyl]-2,4-pyrimidine diamine and 1-1.1 molar equivalents of 1-hydroxy-2-naphthoic acid in a minimum amount of a suitable organic solvent such as acetone, acetonitrile or methyl ethyl ketone, each optionally containing a small amount of water, and subsequent slow cooling of the solution with optional stirring until precipitation of the salt from the solution.

EFFECT: obtained salt has Syk-kinase inhibiting properties and can be used in treating an inflammatory condition such as asthma (I).

12 cl, 6 tbl, 1 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a compound of formula (I) , where Ar denotes each of R2, R3, R4, R5, R4' and R5' denote hydrogen; A denotes C(O); D denotes oxygen or NR8; E denotes CR63R64CR65R66; R63 and R64 denote hydrogen; R65 and R66 independently denote hydrogen or C1-4alkyl; k equals 0; m equals 1; R6 denotes a group -(X)p-Y-(Z)q-R10, or R6 denotes α- or β-branched C3-6alkyl (optionally substituted with C6cycloalkyl); X and Z independently denotes a C1-4alkylene group; p and q are independently equal to 0 or 1; Y denotes a bond; R8 denotes hydrogen; R10 denotes hydrogen or a saturated 5-7-member ring system; R7 denotes a 6-member aromatic ring, optionally substituted with a halogen, carboxyl, C1-6alkyl, C1-2alkoxy or a 5-member heteroaromatic ring (which is optionally substituted with C1-6alkyl); or a pharmaceutically acceptable salt thereof. Compounds of formula (I) or a pharmaceutically acceptable salt thereof are used to produce a medicinal agent for treating respiratory distress syndrome (ARDS), pulmonary emphysema, bronchitis, bronchiectasis, chronic obstructive pulmonary disease (COPD), asthma or rhinitis.

EFFECT: high efficiency of using said compounds.

7 cl, 1 tbl, 102 ex

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