Nitrogen-containing heterobicyclic compounds

FIELD: medicine, pharmaceutics.

SUBSTANCE: there is described a compound of formula [I]: where A cycle represents a benzene cycle optionally having substitute(s) different from R1, R1 represents a group of formula RaSO2NH-, RaSO2NH-CH2- or (Rb)(Rc)NSO2-, Ra represents C1-C6 alkyl group, C3-C10cycloalkyl group, an amino group, 6-10-member monocyclic or bicyclic aryl group or 5-10-member monocyclic or bicyclic heteroaryl group containing 1-2 heteroatoms, chosen from oxygen, sulphur and nitrogen atoms, Rb and Rc are identical or different, and each represents hydrogen atom, C1-C6alkyl group or C3-C10cycloalkyl group, one of R2 and R3 represents hydrogen atom, halogen atom or C1-C6alkyl group, and the other represents hydrogen atom, C1-C6alkyl group, C1-C6alkoxycarbonyl group or phenyl group, or both are combined with each other together with the neighbouring carbon atom to form C3-C10cycloalkyl group, X represents oxygen atom, sulphur atom, or formula group of -NR4-; Y represents a group of formula -C(=O)-, -C(=S)- or CH(R5)-; Ar represents optionally substituted 6-10-member monocyclic or bicyclic aryl group or 5-10-member monocyclic or bicyclic group; Q represents a simple bond, C1-C6alkylene group or C2-C6alkenylene group, or its pharmaceutically acceptable salts There are described specific compounds of formula [I], and also intermediate compounds.

EFFECT: presented compounds exhibit affinity to mineralocorticoid receptor (MR) and are applicable for prevention or treatment of various diseases or diseased states associated with such receptor.

11 cl, 54 tbl, 410 ex

 

The text descriptions are given in facsimile form.

1. The compound of the formula [I]

where cycle And represents a benzene, optionally substituted by 1-3 groups other than R1selected from (a) halogen atom, (b) C1-C6alkyl groups specified alkyl group optionally substituted by 1-3 groups selected from a halogen atom, a hydroxyl group, a C1-C6alkoxygroup, (C) hydroximino the group, (a) C1-C6alkoxygroup, (e) amino, (f) ceanography, (i) C2-C12alkenylphenol group, (j) C1-C7alkanoyloxy group and (k) C2-C10cycloalkyl;
R1represents a group of formula RaSO2NH-, RaSO2NH-CH2- or (Rb)(Rc)NSO2-, and R1substituted in position 7 1.4 to benzoxazinones part, 1,4-benzothiazines part or tetrahydroquinoxaline;
Rarepresents a C1-C6alkyl group, a C3-C10cycloalkyl group, amino group, optionally substituted by 1-2 C1-C6alkyl(s) group(s), 6-10-membered monocyclic or bicyclic aryl group or a 5-10-membered monocyclic or bicyclic heteroaryl group containing 1-2 heteroatom selected from oxygen atom, sulfur and nitrogen, optionally substituted by 1-3 groups selected from a halogen atom, a hydroxyl group, a C1-C6alkyl group, optionally substituted by 1-3 halogen atoms, hydroxy, C1-C6alkyl group, a C1-C6acyloxy C1-C6alkyl group, a C1-C6alkoxy group, optionally substituted by 1-3 groups selected from a halogen atom, a C1-C6alkoxycarbonyl C1-C6alkoxygroup, C1-C6is Citigroup, C1-C6alkylenedioxy, optionally substituted by 1-2 halogen atoms, amino groups, optionally substituted by 1-2 C1-C6alkyl groups, alluminare, C3-C10cycloalkyl group or a C1-C3alkylsulfonyl group;
Rband Rcare the same or different, and each represents a hydrogen atom, a C1-C6alkyl group or a C3-C10cycloalkyl group;
one of R2and R3represents a hydrogen atom, halogen atom or C1-C6alkyl group and the other represents a hydrogen atom, a C1-C6alkyl group, a C1-C6alkoxycarbonyl group or phenyl group, or both are combined with each other together with the adjacent carbon atom with the formation of C3-C10cycloalkyl group;
X represents an oxygen atom, a sulfur atom, or a group of the formula-NR4-;
R4represents a hydrogen atom;
Y represents a group of formula-C(=O)-, -C(=S)- or CH(R5)-;
R5represents a hydrogen atom or a phenyl group;
Ar is a 6-10 membered monocyclic or bicyclic aryl group or a 5-10-membered monocyclic or bicyclic heteroaryl group containing 1-2 heteroatoms selected from the atoms O, S and N, moreover, the mentioned aryl or heteroaryl optionally substituted by 1-3 substituents selected from (a) halogen atom, (b) hydroxyl group, (C) ceanography, (d) and C1-C6alkyl group optionally substituted by 1 to 3 halogen atoms, (e) hydroxy-C1-C6alkyl group, (f) benzyloxy-C1-C6alkyl group, (g) C1-C6alkoxy group optionally substituted by 1 to 3 halogen atoms, (h) C1-C6alkoxycarbonyl C1-C6alkoxygroup, (i) C1-C6allylthiourea, (j) C1-C6alkylenedioxy group, optionally substituted by 1-2 halogen atoms, (k) an amino group optionally substituted by 1-2 C1-C6alkyl groups, (l) alluminare, and the indicated acyl group represents a C1-C6alkanoyloxy group or benzoyloxy group, (m) C3-C10cycloalkyl group and (n) C1-C6alkylsulfonyl group and
Q represents a simple bond, C1-C6alkylenes group or a C2-C6alkynylamino group,
or its pharmaceutically acceptable salt,
with the exception of
N-(4-benzyl-3-oxo-3,4-dihydro-2H-1,4-benzoxazin-7-yl)(p-toluensulfonate);
N-[4-(2-terbisil)-3-oxo-3,4-dihydro-2H-1,4-benzoxazin-7-yl][4-(N-acetylamino)benzosulfimide];
N-[4-(4-terbisil)-3-oxo-3,4-dihydro-2H-1,4-Benz is casin-7-yl][4-(N-acetylamino)benzosulfimide]; and
N-[2,2-dimethyl-4-(1-oxopyridine-2-yl)-3,4-dihydro-2H-1,4-benzoxazin-6-yl]methanesulfonamide.

2. The compound of the formula [I-a]

where cycle And represents a benzene, optionally substituted 1-3 other than R11selected from (a) halogen atom, (b) C1-C6alkyl groups specified alkyl group optionally substituted by 1-3 groups selected from a halogen atom hydroxyl group, a C1-C6alkoxygroup, (c) hydroxyl group, (d) C1-C6alkoxygroup, (e) amino, (f) ceanography, (i) C2-C12alkenylphenol group, (j) C1-C7alkanoyloxy group and C3-C10cycloalkyl,
R11represents a group of formula RaaSO2NH-, RaaSO2NH-CH2- or (Rb)(Rc)NSO2-,
Raarepresents a C1-C6alkyl group, a C3-C10cycloalkyl group, amino group, optionally substituted by 1-2 C1-C6alkyl groups, phenyl group or 5 - or 6-membered monocyclic heteroaryl group containing 1-2 heteroatoms selected from O, S and N,
Rband Rcare the same or different, and each represents a hydrogen atom, a C1-C6alkyl group or a C3-C10cycloalkyl group,
one of R21 and R31represents a hydrogen atom, halogen atom or C1-C6the alkyl group and the other represents a hydrogen atom, halogen, C1-C6alkyl group, a C1-C6alkoxycarbonyl group or phenyl group, or both are combined with each other together with the adjacent carbon atom with the formation of C3-C10cycloalkyl group,
Xarepresents an oxygen atom, a sulfur atom or a group of the formula-NH-,
Yarepresents a group of formula-C(=O)-, -C(=S)- or CH(R51)-,
R51represents a hydrogen atom or phenyl group,
Ar1represents a
(a) phenyl group, optionally substituted by 1-3 groups selected from a halogen atom, a hydroxyl group, ceanography, nitro, C1-C6alkyl group, optionally substituted by 1-3 halogen atoms, hydroxy-C1-C6alkyl group, benzyloxy-C1-C6alkyl group, a C1-C6alkoxygroup, optionally substituted by 1-3 halogen atoms, C1-C6alkoxycarbonyl-C1-C6alkoxygroup, C1-C6allylthiourea, C1-C6alkylenedioxy, optionally substituted by 1-2 halogen atoms, amino groups, optionally substituted by 1-2 C1-C6alkyl groups, C1-C7 alkanolamines, C1-C6alkoxycarbonyl group, C3-C10cycloalkyl group and C1-C6alkylsulfonyl group;
(b) thienyl group, optionally substituted by 1-2 groups selected from a halogen atom and trihalogen-C1-C6alkyl groups, and specified thienyl group optionally condensed with a benzene cycle;
(c) pyridyloxy group, optionally substituted by 1-2 groups selected from a halogen atom, nitro, C1-C6alkyl groups and trihalogen-C1-C6alkyl group;
(d) pyrimidinyl group optionally substituted by a halogen atom;
(e) pinolillo group;
(f) pyridazinyl group optionally substituted by a halogen atom;
(g) pyrrolidinyl group;
(h) follow group optionally condensed with a benzene cycle;
(l) thiazolidine group optionally condensed with a benzene cycle;
(j) imidazolidinyl group optionally condensed with a benzene cycle, and optionally substituted C1-C6alkyl group, or
(k) naftalina group and
Q represents a simple bond, C1-C6alkylenes group or a C2-C6alkynylamino group,
or its pharmaceutically acceptable salt.

3. The compound according to claim 2, where the cycle And presented yet a benzene cycle, optionally substituted by a group other than R11selected from a halogen atom, a hydroxyl group, a C1-4is an alkyl group, trihalogen-C1-4-alkyl groups, hydroxy-C1-4is an alkyl group, a C1-4-alkoxy-C1-4is an alkyl group, a C1-4-alkoxygroup, amino, C2-4-alkenylphenol group2-5-alkanoyloxy group and C3-8-cycloalkyl group,
R11represents a C1-4-alkylsulfonamides, C3-6-cycloalkylcarbonyl, C1-4-alkylaminocarbonyl group, C1-4-alkylsulfonamides group, aminosulfonyl, di(C1-4-alkyl)aminosulfonyl or mono(C1-4-alkyl)aminosulfonyl group,
one of R21and R31represents a hydrogen atom or a C1-4is an alkyl group and the other represents a hydrogen atom, a halogen atom, a C1-4is an alkyl group or phenyl group, or R21and R31both are combined with each other with formation of C3-8-cycloalkyl group,
Ar1represents (a) phenyl group, optionally substituted by 1-3 groups selected from a halogen atom, a hydroxyl group, ceanography, nitro, C1-4is an alkyl group, a C1-4is an alkyl group substituted by 1-3 halogen atoms, hydroxy-C1-4-alkyl the Noah group, benzyloxy-C1-4is an alkyl group, a C1-4-alkoxygroup, C1-4-alkoxygroup substituted by 1-3 halogen atoms, C3-8-cycloalkyl group1-4-allylthiourea, amino group, optionally substituted With 1-21-4-alkyl groups, With2-5-alkanolamines,1-4-alkylenedioxy and C1-4-alkylenedioxy substituted by 1-2 halogen atoms; (b) naftalina group; (C) thienyl (or benzothiazoline) group, optionally substituted by 1-2 groups selected from a halogen atom and trihalogen-C1-4is an alkyl group; (d) pyridyloxy group, optionally substituted by 1-2 groups selected from a halogen atom, nitro, C1-4is an alkyl group and trihalogen-C1-4is an alkyl group; or (e) benzofuranyl group,
Q represents a simple bond or a C1-4-alkylenes group, and
Yarepresents a group of formula-C(=O)-, -C(=S) -, or-CH2-.

4. The compound according to claim 3, where R21and R31represents a hydrogen atom.

5. The compound according to claim 3, where R21represents a hydrogen atom, and R31represents a C1-4is an alkyl group.

6. The compound according to claim 3, where R21represents a hydrogen atom or a C1-4is an alkyl group, and R31represents a phenyl group.

7. The compound according to claim 3 where R and R31represents a C1-4is an alkyl group.

8. The compound according to claim 3, where R21represents a hydrogen atom, and R31represents a halogen atom.

9. The compound according to claim 3, where R21and R31together with each other together with the adjacent carbon atom with the formation of C3-8-cycloalkyl group.

10. A compound selected from the group which includes
N-(3-oxo-2,4-diphenyl-3,4-dihydro-2H-1,4-benzoxazin-7-yl)methanesulfonamide;
N-[4-(4-forfinal)-3-oxo-2-phenyl-3,4-dihydro-2H-1,4-benzoxazin-7-yl]methanesulfonamide;
N-[4-(4-chlorophenyl)-3-oxo-2-phenyl-3,4-dihydro-2H-1,4-benzoxazin-7-yl]methanesulfonamide;
N-(2,2-dimethyl-3-oxo-4-phenyl-3,4-dihydro-2H-1,4-benzoxazin-7-yl)methanesulfonamide;
N-[4-(4-forfinal)-2,2-dimethyl-3-oxo-3,4-dihydro-2H-1,4-benzoxazin-7-yl]methanesulfonamide;
N-[4-(4-chlorophenyl)-2,2-dimethyl-3-oxo-3,4-dihydro-2H-1,4-benzoxazin-7-yl]methanesulfonamide;
N-[4-(3,4-differenl)-2,2-dimethyl-3-oxo-3,4-dihydro-2H-1,4-benzoxazin-7-yl]methanesulfonamide;
N-[4-(4-fluoro-3-were)-2,2-dimethyl-3-oxo-3,4-dihydro-2H-1,4-benzoxazin-7-yl]methanesulfonamide;
N-[4-(3-chloro-4-forfinal)-2,2-dimethyl-3-oxo-3,4-dihydro-2H-1,4-benzoxazin-7-yl]methanesulfonamide;
N-[4-(4-methoxyphenyl)-2,2-dimethyl-3-oxo-3,4-dihydro-2H-1,4-benzoxazin-7-yl]methanesulfonamide;
N-[4-(4-forfinal)-2,2-dimethyl-3-oxo-3,4-dihydro-2H-1,4-benzoxazin-7-yl]econsultant;br/> N-[4-(5-herperidin-2-yl)-2,2-dimethyl-3-oxo-3,4-dihydro-2H-1,4-benzoxazin-7-yl]methanesulfonamide;
N-(4-benzyl-2,2-dimethyl-3-oxo-3,4-dihydro-2H-1,4-benzoxazin-7-yl)methanesulfonamide;
N-(4-benzyl-3-oxo-3,4-dihydro-2H-1,4-benzoxazin-7-yl)methanesulfonamide;
N-[4-(4-forfinal)-2-methyl-3-oxo-3,4-dihydro-2H-1,4-benzoxazin-7-yl]methanesulfonamide;
4-(4-forfinal)-N,2,2-trimethyl-3-oxo-3,4-dihydro-2H-1,4-benzoxazin-7-sulfonamide;
N-[4-(5-chloro-2-thienyl)-2,2-dimethyl-3-oxo-3,4-dihydro-2H-1,4-benzoxazin-7-yl]methanesulfonamide;
N'-[4-(4-forfinal)-2,2-dimethyl-3-oxo-3,4-dihydro-2H-1,4-benzoxazin-7-yl]-N,N-dimethylsulfone;
N-[4-(4-forfinal)-2,2-dimethyl-3,4-dihydro-2H-1,4-benzoxazin-7-yl]methanesulfonamide;
N-[2,2-dimethyl-3-oxo-4-(3-thienyl)-3,4-dihydro-2H-1,4-benzoxazin-7-yl]methanesulfonamide;
N-[4-(4-forfinal)-3-oxo-3,4-dihydrospiro[1,4-benzoxazine-2,1'-CYCLOBUTANE]-7-yl]methanesulfonamide;
N-[1-(4-forfinal)-3,3-dimethyl-2-oxo-1,2,3,4-tetrahydroquinoxalin-6-yl]methanesulfonamide;
N-[4-(4-fluoro-3-trifluoromethyl)phenyl]-2,2-dimethyl-3-oxo-3,4-dihydro-2H-1,4-benzoxazin-7-yl]methanesulfonamide;
N-[2,2-dimethyl-4-(4-were)-3-oxo-3,4-dihydro-2H-1,4-benzoxazin-7-yl]methanesulfonamide;
N-[4-(4-forfinal)-3-oxo-3,4-dihydrospiro[1,4-benzoxazine-2,1'-cyclopropane]-7-yl]methanesulfonamide;
N-[2,2-diethyl-4-(4-forfinal)-3-oxo-3,4-dihydro-2H-1,4-benzoxazin-7-yl]methanesulfonamide;
N-[2-ethyl-4-(4-forfinal)-3-oxo-3,4-dihydro-2H-1,4-benzo who Sasin-7-yl]methanesulfonamide;
N-[2,2-dimethyl-3-oxo-4-[(4-tripometer)phenyl]-3,4-dihydro-2H-1,4-benzoxazin-7-yl]methanesulfonamide;
N-[4-(4-forfinal)-2,2-dimethyl-3-oxo-3,4-dihydro-2H-1,4-benzoxazin-7-yl]sulphonamide;
N-[4-(2,4-differenl)-2,2-dimethyl-3-oxo-3,4-dihydro-2H-1,4-benzoxazin-7-yl]methanesulfonamide;
N-[4-(4-forfinal)-2,2-dimethyl-3-thioxo-3,4-dihydro-2H-1,4-benzoxazin-7-yl]methanesulfonamide;
N-[4-(4-fluoro-2-were)-2,2-dimethyl-3-oxo-3,4-dihydro-2H-1,4-benzoxazin-7-yl]methanesulfonamide;
N-[4-(4-chloro-3-methoxyphenyl)-2,2-dimethyl-3-oxo-3,4-dihydro-2H-1,4-benzoxazin-7-yl]methanesulfonamide;
N-[4-(4-fluoro-3-methoxyphenyl)-2,2-dimethyl-3-oxo-3,4-dihydro-2H-1,4-benzoxazin-7-yl]methanesulfonamide;
4-(4-fluoro-3-were)-N,2,2-trimethyl-3-oxo-3,4-dihydro-2H-1,4-benzoxazin-7-sulfonamide;
N-[4-[3-(dimethylamino)-4-forfinal]-2,2-dimethyl-3-oxo-3,4-dihydro-2H-1,4-benzoxazin-7-yl]methanesulfonamide;
N-[4-(3-chloro-4-forfinal)-3-oxo-3,4-dihydro-2H-1,4-benzoxazin-7-yl]methanesulfonamide;
N-[4-(2-chloro-4-forfinal)-2,2-dimethyl-3-oxo-3,4-dihydro-2H-1,4-benzoxazin-7-yl]methanesulfonamide;
N-[4-(4-chloro-2-forfinal)-2,2-dimethyl-3-oxo-3,4-dihydro-2H-1,4-benzoxazin-7-yl]methanesulfonamide;
N-[4-(4-chloro-2-were)-2,2-dimethyl-3-oxo-3,4-dihydro-2H-1,4-benzoxazin-7-yl]methanesulfonamide;
N-[4-(4-bromophenyl)-2,2-dimethyl-3-oxo-3,4-dihydro-2H-1,4-benzoxazin-7-yl]methanesulfonamide;
N-[4-(4-forfinal)-2,2,6-trimethyl-3-oxo-3,4-dihydro-2H-1,4-benzoxazin-7-yl]IU is unsulfonated;
N-[6-amino-4-(4-forfinal)-2,2-dimethyl-3-oxo-3,4-dihydro-2H-1,4-benzoxazin-7-yl]methanesulfonamide;
N-[4-[3-(deformity)-4-forfinal]-2,2-dimethyl-3-oxo-3,4-dihydro-2H-1,4-benzoxazin-7-yl]methanesulfonamide;
4-(4-chlorophenyl)-N,2,2-trimethyl-3-oxo-3,4-dihydro-2H-1,4-benzoxazin-7-sulfonamide;
N-[4-(4-chloro-2-cyanophenyl)-2,2-dimethyl-3-oxo-3,4-dihydro-2H-1,4-benzoxazin-7-yl]methanesulfonamide;
4-(4-bromophenyl)-N,2,2-trimethyl-3-oxo-3,4-dihydro-2H-1,4-benzoxazin-7-sulfonamide;
N-[4-(5-chloropyridin-2-yl)-2,2-dimethyl-3-oxo-3,4-dihydro-2H-1,4-benzoxazin-7-yl]methanesulfonamide;
N-[5-chloro-4-(4-forfinal)-2,2-dimethyl-3-oxo-3,4-dihydro-2H-1,4-benzoxazin-7-yl]methanesulfonamide;
N-[4-(4-bromo-2-were)-2,2-dimethyl-3-oxo-3,4-dihydro-2H-1,4-benzoxazin-7-yl]methanesulfonamide;
N-[4-[4-chloro-3-(trifluoromethyl)phenyl]-2,2-dimethyl-3-oxo-3,4-dihydro-2H-1,4-benzoxazin-7-yl]methanesulfonamide;
N-[4-[3-fluoro-4-(trifluoromethyl)phenyl]-2,2-dimethyl-3-oxo-3,4-dihydro-2H-1,4-benzoxazin-7-yl]methanesulfonamide;
N-[4-(4-chloro-3-forfinal)-2,2-dimethyl-3-oxo-3,4-dihydro-2H-1,4-benzoxazin-7-yl]methanesulfonamide;
N-[4-(4-chloro-3-were)-2,2-dimethyl-3-oxo-3,4-dihydro-2H-1,4-benzoxazin-7-yl]methanesulfonamide;
N-[4-(3-fluoro-4-were)-2,2-dimethyl-3-oxo-3,4-dihydro-2H-1,4-benzoxazin-7-yl]methanesulfonamide;
4-(4-chloro-2-were)-N,2,2-trimethyl-3-oxo-3,4-dihydro-2H-1,4-benzoxazin-7-sulfonamide;
N-[4-(2,4-dimetilfenil)-2,2-dimethyl-3-oxo-3,4-digitron-1,4-benzoxazin-7-yl]methanesulfonamide;
N-[4-(3-chloro-4-were)-2,2-dimethyl-3-oxo-3,4-dihydro-2H-1,4-benzoxazin-7-yl]methanesulfonamide;
N-[4-(3,4-debtor-5-methoxyphenyl)-2,2-dimethyl-3-oxo-3,4-dihydro-2H-1,4-benzoxazin-7-yl]methanesulfonamide;
N-[4-(3,4-dichlorophenyl)-2,2-dimethyl-3-oxo-3,4-dihydro-2H-1,4-benzoxazin-7-yl]methanesulfonamide;
N-[2,2-dimethyl-4-(2-naphthyl)-3-oxo-3,4-dihydro-2H-1,4-benzoxazin-7-yl]methanesulfonamide;
N-[4-(4-fluoro-2,6-dimetilfenil)-2,2-dimethyl-3-oxo-3,4-dihydro-2H-1,4-benzoxazin-7-yl]methanesulfonamide;
N-[5-bromo-4-(4-forfinal)-2,2-dimethyl-3-oxo-3,4-dihydro-2H-1,4-benzoxazin-7-yl]methanesulfonamide;
N-[4-(5-chloro-2-were)-2,2-dimethyl-3-oxo-3,4-dihydro-2H-1,4-benzoxazin-7-yl]methanesulfonamide;
N-[5-chloro-4-(4-chlorophenyl)-2,2-dimethyl-3-oxo-3,4-dihydro-2H-1,4-benzoxazin-7-yl]methanesulfonamide;
N-[4-(4-forfinal)-2,2,5-trimethyl-3-oxo-3,4-dihydro-2H-1,4-benzoxazin-7-yl]methanesulfonamide;
N-[4-(4-bromo-3-were)-2,2-dimethyl-3-oxo-3,4-dihydro-2H-1,4-benzoxazin-7-yl]methanesulfonamide;
N-[4-(2,2-debtor-1,3-benzodioxol-5-yl)-2,2-dimethyl-3-oxo-3,4-dihydro-2H-1,4-benzoxazin-7-yl]methanesulfonamide;
N-(4-mesityl-2,2-dimethyl-3-oxo-3,4-dihydro-2H-1,4-benzoxazin-7-yl)methanesulfonamide;
N-[4-(2,6-dimetilfenil)-2,2-dimethyl-3-oxo-3,4-dihydro-2H-1,4-benzoxazin-7-yl]methanesulfonamide;
N-[4-(4-chloro-2,6-dimetilfenil)-2,2-dimethyl-3-oxo-3,4-dihydro-2H-1,4-benzoxazin-7-yl]methanesulfonamide;
N-[4-(5-bromo-3-methylpyridin-2-yl)-2,2-dimethyl-3-ox is -3,4-dihydro-2H-1,4-benzoxazin-7-yl]methanesulfonamide;
N-[5-fluoro-4-(4-forfinal)-2,2-dimethyl-3-oxo-3,4-dihydro-2H-1,4-benzoxazin-7-yl]methanesulfonamide;
N-[4-(3,5-dichloropyridine-2-yl)-2,2-dimethyl-3-oxo-3,4-dihydro-2H-1,4-benzoxazin-7-yl]methanesulfonamide;
N-[4-(4-fluoro-2,3-dimetilfenil)-2,2-dimethyl-3-oxo-3,4-dihydro-2H-1,4-benzoxazin-7-yl]methanesulfonamide;
N-[4-(3-chloro-2-were)-2,2-dimethyl-3-oxo-3,4-dihydro-2H-1,4-benzoxazin-7-yl]methanesulfonamide;
N-[4-(5-fluoro-2-were)-2,2-dimethyl-3-oxo-3,4-dihydro-2H-1,4-benzoxazin-7-yl]methanesulfonamide;
N-[2,2-dimethyl-3-oxo-4-(1-phenylethyl)-3,4-dihydro-2H-1,4-benzoxazin-7-yl]methanesulfonamide;
N-[2,2-dimethyl-4-(3-methylbenzyl)-3-oxo-3,4-dihydro-2H-1,4-benzoxazin-7-yl]methanesulfonamide;
N-[2,2-dimethyl-4-[2-methyl-5-(trifluoromethyl)phenyl]-3-oxo-3,4-dihydro-2H-1,4-benzoxazin-7-yl]methanesulfonamide;
N-[2,2-dimethyl-3-oxo-4-(2,4,6-tryptophanyl)-3,4-dihydro-2H-1,4-benzoxazin-7-yl]methanesulfonamide;
2-chloro-5-[2,2-dimethyl-7-[(methylsulphonyl)amino]-3-oxo-2,3-dihydro-4H-1,4-benzoxazin-4-yl]benzyl benzoate;
N-[4-(4-chloro-2-methoxy-5-were)-2,2-dimethyl-3-oxo-3,4-dihydro-2H-1,4-benzoxazin-7-yl]methanesulfonamide;
N-[4-(6-chloro-2,2-debtor-1,3-benzodioxol-5-yl)-2,2-dimethyl-3-oxo-3,4-dihydro-2H-1,4-benzoxazin-7-yl]methanesulfonamide;
N-[2,2-dimethyl-4-(3-methyl-5-nitropyridine-2-yl)-3-oxo-3,4-dihydro-2H-1,4-benzoxazin-7-yl]methanesulfonamide;
N-[4-(5-chloro-3-methylpyridin-2-yl)-2,2-dimethyl-3-oxo-3,4-dihydro-2H-1,4-benzoxazin-7-yl]methane is sulfonamid;
N-[4-[4-fluoro-2-(trifluoromethyl)phenyl]-2,2-dimethyl-3-oxo-3,4-dihydro-2H-1,4-benzoxazin-7-yl]methanesulfonamide;
N-[2,2-dimethyl-4-[2-methyl-4-(trifluoromethyl)phenyl]-3-oxo-3,4-dihydro-2H-1,4-benzoxazin-7-yl]methanesulfonamide;
N-[4-(4-forfinal)-2,2-dimethyl-3-oxo-5-vinyl-3,4-dihydro-2H-1,4-benzoxazin-7-yl]methanesulfonamide;
N-[4-(4-chlorophenyl)-5-fluoro-2,2-dimethyl-3-oxo-3,4-dihydro-2H-1,4-benzoxazin-7-yl]methanesulfonamide;
N-[4-(5-chloropyridin-2-yl)-5-fluoro-2,2-dimethyl-3-oxo-3,4-dihydro-2H-1,4-benzoxazin-7-yl]methanesulfonamide;
N-[4-[3-chloro-5-(trifluoromethyl)pyridin-2-yl]-2,2-dimethyl-3-oxo-3,4-dihydro-2H-1,4-benzoxazin-7-yl]methanesulfonamide;
N-[4-(3-chlorophenyl)-2,2-dimethyl-3-oxo-3,4-dihydro-2H-1,4-benzoxazin-7-yl]methanesulfonamide;
N-[4-(5-bromo-6-methylpyridin-2-yl)-2,2-dimethyl-3-oxo-3,4-dihydro-2H-1,4-benzoxazin-7-yl]methanesulfonamide;
N-[5-fluoro-4-(5-herperidin-2-yl)-2,2-dimethyl-3-oxo-3,4-dihydro-2H-1,4-benzoxazin-7-yl]methanesulfonamide;
N-[2,2-dimethyl-3-oxo-4-[5-(trifluoromethyl)-2-thienyl]-3,4-dihydro-2H-1,4-benzoxazin-7-yl]methanesulfonamide;
N-[4-(6-chloro-4-methylpyridin-3-yl)-2,2-dimethyl-3-oxo-3,4-dihydro-2H-1,4-benzoxazin-7-yl]methanesulfonamide;
N-[4-(5-bromopyridin-2-yl)-2,2-dimethyl-3-oxo-3,4-dihydro-2H-1,4-benzoxazin-7-yl]methanesulfonamide;
N-[4-[4-chloro-3-(hydroxymethyl)phenyl]-2,2-dimethyl-3-oxo-3,4-dihydro-2H-1,4-benzoxazin-7-yl]methanesulfonamide;
N-[4-(6-bromo-5-methylpyridin-3-yl)-2,2-dimethyl-3-oxo-3,4-dihydro-2H-1,4-b is isoxazine-7-yl]methanesulfonamide;
N-[4-(6-chloro-2-methylpyridin-3-yl)-2,2-dimethyl-3-oxo-3,4-dihydro-2H-1,4-benzoxazin-7-yl]methanesulfonamide;
N-{2,2-dimethyl-3-oxo-4-[5-(trifluoromethyl)pyridin-2-yl]-3,4-dihydro-2H-1,4-benzoxazin-7-yl}methanesulfonamide;
N-{2,2-dimethyl-4-[3-methyl-6-(trifluoromethyl)pyridin-2-yl]-3-oxo-3,4-dihydro-2H-1,4-benzoxazin-7-yl}methanesulfonamide;
N-[4-(5-chloro-3-herperidin-2-yl)-2,2-dimethyl-3-oxo-3,4-dihydro-2H-1,4-benzoxazin-7-yl]methanesulfonamide;
N-[4-(3-chlorophenyl)-5-fluoro-2,2-dimethyl-3-oxo-3,4-dihydro-2H-1,4-benzoxazin-7-yl]methanesulfonamide;
N-[4-(5-bromopyridin-2-yl)-5-fluoro-2,2-dimethyl-3-oxo-3,4-dihydro-2H-1,4-benzoxazin-7-yl]methanesulfonamide;
N-[4-(5-chloro-3-methylpyridin-2-yl)-5-fluoro-2,2-dimethyl-3-oxo-3,4-dihydro-2H-1,4-benzoxazin-7-yl]methanesulfonamide;
N-{5-fluoro-2,2-dimethyl-3-oxo-4-[5-(trifluoromethyl)pyridin-2-yl]-3,4-dihydro-2H-1,4-benzoxazin-7-yl}methanesulfonamide;
N-[4-(5-fluoro-3-methylpyridin-2-yl)-2,2-dimethyl-3-oxo-3,4-dihydro-2H-1,4-benzoxazin-7-yl]methanesulfonamide;
N-[4-(5-chloro-3-herperidin-2-yl)-5-fluoro-2,2-dimethyl-3-oxo-3,4-dihydro-2H-1,4-benzoxazin-7-yl]methanesulfonamide;
N-[4-[4-chloro-3-(hydroxymethyl)phenyl]-5-fluoro-2,2-dimethyl-3-oxo-3,4-dihydro-2H-1,4-benzoxazin-7-yl]methanesulfonamide;
2-chloro-5-[5-fluoro-2,2-dimethyl-7-[(methylsulphonyl)amino]-3-oxo-2,3-dihydro-4H-1,4-benzoxazin-4-yl]benzyl benzoate;
N-[4-(2,6-dimethylpyridin-3-yl)-2,2-dimethyl-3-oxo-3,4-dihydro-2H-1,4-benzoxazin-7-yl]methanesulfonamide;
N-[5-cycle is propyl-4-(4-forfinal)-2,2-dimethyl-3-oxo-3,4-dihydro-2H-1,4-benzoxazin-7-yl]methanesulfonamide;
N-[5-fluoro-4-[3-fluoro-4-(trifluoromethyl)phenyl]-2,2-dimethyl-3-oxo-3,4-dihydro-2H-1,4-benzoxazin-7-yl]methanesulfonamide;
N-[5-fluoro-2,2-dimethyl-3-oxo-4-[4-(trifluoromethyl)phenyl]-3,4-dihydro-2H-1,4-benzoxazin-7-yl]methanesulfonamide;
N-[5-fluoro-4-[4-fluoro-3-(trifluoromethyl)phenyl]-2,2-dimethyl-3-oxo-3,4-dihydro-2H-1,4-benzoxazin-7-yl]methanesulfonamide;
N-[4-(3-chloro-4-forfinal)-5-fluoro-2,2-dimethyl-3-oxo-3,4-dihydro-2H-1,4-benzoxazin-7-yl]methanesulfonamide;
N-[4-(3,4-differenl)-5-fluoro-2,2-dimethyl-3-oxo-3,4-dihydro-2H-1,4-benzoxazin-7-yl]methanesulfonamide;
N-[5-fluoro-4-(5-fluoro-6-methylpyridin-2-yl)-2,2-dimethyl-3-oxo-3,4-dihydro-2H-1,4-benzoxazin-7-yl]methanesulfonamide;
N-[4-(6-chloro-2-methylpyridin-3-yl)-5-fluoro-2,2-dimethyl-3-oxo-3,4-dihydro-2H-1,4-benzoxazin-7-yl]methanesulfonamide;
N-[4-(4-chloro-2-forfinal)-5-fluoro-2,2-dimethyl-3-oxo-3,4-dihydro-2H-1,4-benzoxazin-7-yl]methanesulfonamide;
N-[4-(5-fluoro-6-methylpyridin-3-yl)-2,2-dimethyl-3-oxo-3,4-dihydro-2H-1,4-benzoxazin-7-yl]methanesulfonamide;
N-[4-(bestien-2-yl)-2,2-dimethyl-3-oxo-3,4-dihydro-2H-1,4-benzoxazin-7-yl]methanesulfonamide;
N-[4-(benzofuran-2-yl)-2,2-dimethyl-3-oxo-3,4-dihydro-2H-1,4-benzoxazin-7-yl]methanesulfonamide;
N-[4-[2-chloro-6-(trifluoromethyl)pyridin-3-yl]-2,2-dimethyl-3-oxo-3,4-dihydro-2H-1,4-benzoxazin-7-yl]methanesulfonamide;
N-[4-(4-forfinal)-5-(methoxymethyl)-2,2-dimethyl-3-oxo-3,4-dihydro-2H-1,4-benzoxazin-7-yl]methanesulfonamide;
N-[2,2-dimethyl-4-[3-methyl-5-(three is tormentil)pyridine-2-yl]-3-oxo-3,4-dihydro-2H-1,4-benzoxazin-7-yl]methanesulfonamide;
N-[2,2-dimethyl-4-[2-methyl-6-(trifluoromethyl)pyridin-3-yl]-3-oxo-3,4-dihydro-2H-1,4-benzoxazin-7-yl]methanesulfonamide;
N-[2,2-dimethyl-4-[2-methyl-5-(trifluoromethyl)pyridin-3-yl]-3-oxo-3,4-dihydro-2H-1,4-benzoxazin-7-yl]methanesulfonamide;
N-[5-ethyl-4-(4-forfinal)-2,2-dimethyl-3-oxo-3,4-dihydro-2H-1,4-benzoxazin-7-yl]methanesulfonamide;
N-[5-fluoro-2,2-dimethyl-3-oxo-4-[5-(trifluoromethyl)-2-thienyl]-3,4-dihydro-2H-1,4-benzoxazin-7-yl]methanesulfonamide;
N-[5-fluoro-4-(5-fluoro-3-methylpyridin-2-yl)-2,2-dimethyl-3-oxo-3,4-dihydro-2H-1,4-benzoxazin-7-yl]methanesulfonamide;
N-[4-(6-chloro-2,2-debtor-1,3-benzodioxol-5-yl)-5-fluoro-2,2-dimethyl-3-oxo-3,4-dihydro-2H-1,4-benzoxazin-7-yl]methanesulfonamide;
N-[4-(2,2-debtor-1,3-benzodioxol-5-yl)-5-fluoro-2,2-dimethyl-3-oxo-3,4-dihydro-2H-1,4-benzoxazin-7-yl]methanesulfonamide;
N-[4-(5-bromo-3-methylpyridin-2-yl)-5-fluoro-2,2-dimethyl-3-oxo-3,4-dihydro-2H-1,4-benzoxazin-7-yl]methanesulfonamide;
N-[5-fluoro-2,2-dimethyl-4-[3-methyl-5-(trifluoromethyl)pyridin-2-yl]-3-oxo-3,4-dihydro-2H-1,4-benzoxazin-7-yl]methanesulfonamide;
N-[4-(4-chloro-2-were)-5-fluoro-2,2-dimethyl-3-oxo-3,4-dihydro-2H-1,4-benzoxazin-7-yl]methanesulfonamide;
N-[4-(3-amino-4-forfinal)-2,2-dimethyl-3-oxo-3,4-dihydro-2H-1,4-benzoxazin-7-yl]methanesulfonamide;
N-[4-(4-fluoro-2-methoxyphenyl)-2,2-dimethyl-3-oxo-3,4-dihydro-2H-1,4-benzoxazin-7-yl]methanesulfonamide;
4-(3-chloro-4-forfinal)-N,2,2-trimethyl-3-oxo-3,4-dihydro-2H-1,4-benzoxazin-7-sulfones is;
N-{2,2-dimethyl-3-oxo-4-[3-(trifluoromethyl)phenyl]-3,4-dihydro-2H-1,4-benzoxazin-7-yl} methanesulfonamide and
N-{2,2-dimethyl-4-[2-methyl-3-(trifluoromethyl)phenyl]-3-oxo-3,4-dihydro-2H-1,4-benzoxazin-7-yl}methanesulfonamide;
or its pharmaceutically acceptable salt.

11. The compound of the formula [ii]

where the cycle And2represents a benzene, optionally substituted by 1-3 groups other than R00selected from (a) halogen atom, (b) C1-C6alkyl groups specified alkyl group optionally substituted by 1-3 groups selected from a halogen atom, a hydroxyl group, a C1-C6alkoxygroup, (C) hydroxyl group, (d) C1-C6alkoxygroup, (e) amino, (f) ceanography, (i) C2-C12alkenylphenol group, (j)1-C7alkanoyloxy group and C3-C10cycloalkyl;
R00is a nitro-group or amino group;
one of R22and R32represents a hydrogen atom or a C1-C6alkyl group and the other represents a hydrogen atom, a C1-C6alkyl group, a C1-C6alkoxycarbonyl group or phenyl group, or both are combined with each other together with the adjacent carbon atom with the formation of C3-C10cycloalkyl group;
Xbis Soboh the atom of O or S or a group-NR 4-where R4represents a hydrogen atom;
Ybrepresents a group of formula-C(=O)-, -C(=S) -, or-CH(R5)-, where R5represents a hydrogen atom or phenyl group,
Ar2represents a 6-10 membered monocyclic or bicyclic aryl group or a 5-10-membered monocyclic or bicyclic heteroaryl group containing 1-2 heteroatoms selected from the atoms O, S and N, and the specified aryl or heteroaryl optionally substituted by 1-3 substituents selected from (a) halogen atom, (b) hydroxyl group, (C) ceanography, (d) and C1-C6alkyl group optionally substituted by 1 to 3 halogen atoms, (e) hydroxy-C1-C6alkyl group, (f) benzoyloxy-C1-C6alkyl group, (g) C1-C6alkoxygroup, optionally substituted by 1 to 3 halogen atoms, (h) C1-C6alkoxycarbonyl-C1-C6alkoxygroup, (i) C1-C6allylthiourea, (j) C1-C6alkylenedioxy, optionally substituted by 1-2 halogen atoms, (k) an amino group optionally substituted With 1-21-C6alkyl groups, (l) alluminare, and the indicated acyl group represents a C1-C6alkanoyloxy group or benzoyloxy group, (m)3-C10cycloalkyl group and (n)1-C6alkylsulfonyl group;
Q represents a simple link1-C6alkylenes group or1-C6alkynylamino group, or its pharmaceutically acceptable salt.



 

Same patents:

FIELD: chemistry.

SUBSTANCE: invention relates to novel compounds of formula (I) , where X is C(R8R9), NR10, O, S; R1 is phenyl which is substituted with 1-3 substitutes selected from a group which includes halogen, hydroxy group, lower alkyl, hydroxy-lower alkyl and CN; R2 is hydrogenor lower alkyl; R3 and R4 are hydrogen; R5 and R6 are hydrogen; R7 is oxadiazolyl or triazolyl, where oxadiazolyl or triazolyl is substituted with R11; R8 and R9 denote hydrogen; R10 denotes hydrogen, lower alkyl, lower alkyl-carbonyl or lower alkyl-sulfonyl, R11 denotes aryl or hetearyl, selected from a group comprising pyridinyl, pyrazinyl, pyrimidinyl, pyridinyl-2-one, oxadiazolyl, indazolyl, 1,3-dihydrobenzimidazol-2-one, 1,3-dihydroindol-2-one, benzotriazolyl, imidazopyridinyl, triazolepyridinyl, tetrazolepyridinyl, benzimidazolyl, 2-oxo-2,3-dihydro-1H-indol-5-yl, pyrimidin-4-one, furanyl, thiadiazolyl, pyrazolyl, isoxazolyl, pyrimidin-2,4-one, benzoxazin-3-one, 1,4-dihydrobenzoxazin-2-one, indolyl, thiophenyl, oxazolyl, benzooxazin-2-one; 3,4-dihydroquinazolin-2-one, pyridazinyl, quinoxalinyl, benzothiazolyl, benzothiadiazolyl, naphthyridinyl, cinnolinyl, 1,4-dihydroquinoxalin-2,3-dione and 1,2-dihydroindazol-3-one, where the aryl or heteroaryl is optionally substituted with 1-3 substitutes selected from a group which includes lower alkyl, hydroxy group, B(OH)2, carboxy-lower alkoxy group, carbamoyl-lower alkoxy group, cyano group, hydroxy-lower alkyl, fluoro-lower alkyl, lower alkoxy group, halogen, S(O2)R13, C(O)R14, NO2, NR15R16, phenyl-lower alkoxy group, [1,3,4]oxadiazol-2-one, oxadiazolyl, triazolyl and isoxazolyl, imidazolyl, pyrazolyl, tetrazolyl, pyrrolyl, where imidazolyl is optionally substituted with lower alkyl, and where isoxazolyl is substituted with lower alkyl; R12 denotes hydrogen or lower alkyl; R13 denotes lower alkyl, NR17R18 or fluoro-lower alkyl; R14 denotes NR19 R20, lower alkoxy group, lower alkenyl-oxy group or lower alkyl; R15 and R16 independently denote hydrogen, lower alkyl, lower alkyl-carbonyl, lower alkyl-SO2, lower alkenyl-oxycarbonyl and lower alkyl-NH-carbonyl; or NR15R16 denotes heterocyclyl selected from a group which includes morpholinyl, thiomorpholinyl, 1,1-dioxothiomorpholinyl, piperidinyl, piperidin-2-one, piperazin-2-one, 8-oxa-3-aza-bicyclo[3.2.1]octyl, piperazinyl, pyrrolidinyl, 1,1-dioxoisothiazolidinyl, pyrrolidin-2-one, imidazolidine-1,4-dione, 2,4-dihydro[1.2.4]triazol-3-one, pyrrolidine-2,5-dione, azetidin-2-one and 1,3-dihydroimidazol-2-one, where the heterocycle is optionally substituted with hydroxy-lower alkyl or lower alkyl-carbonyl; R17 and R18 independently denote hydrogen, lower alkyl, hydroxy-lower alkyl, lower alkoxy group-lower alkyl; or NR17 R18 denotes morpholinyl; R19 and R20 independently denote hydrogen, lower alkyl, cycloalkyl, hydroxy-lower alkyl, lower alkoxy group-lower alkyl or cyano-lower alkyl; or NR19 R20 denotes heterocyclyl selected from a group which includes morpholinyl, pyrrolidinyl, 8-oxa-3-aza-bicyclo[3.2.1]octyl, piperidinyl, piperazinyl, piperazin-2-one, thiazolidinyl, thiomorpholinyl, 1,3,8-triaza-spiro[4.5]decane-2,4-dione and spiro(1- phthalan)piperidin-4-yl, where the heterocyclyl is optionally substituted with a hydroxy group, lower alkyl-(SO2), lower alkyl, lower alkyl-carbonyl or lower alkoxy group, carboxyl group, carbamoyl, cyano group and phenyl; and to their pharmaceutically acceptable salts. Invention also pertains to a pharmaceutical composition.

EFFECT: obtaining novel biologically active compounds which inhibit hepatic carnitine palmitoyltransferase 1 (L-CPT1).

35 cl, 565 ex, 10 tbl

FIELD: chemistry.

SUBSTANCE: invention relates to a novel salt form of 5-[(2R,5S)-5-methyl-4-propylmorpholin-2-yl]piridine-2-amine (I): , and specifically to 5-[2R,5S)-5-methyl-4-propylmorpholin-2-yl]pyridine-2-amine di-(1S)-camphorsulphonate (di-S-camsylate), to a pharmaceutical composition having effect on dopamine D3 receptor, as well use of the given compound in preparing a medicinal agent for treating sexual dysfunction and neuropsychiatric disorders and a method of obtaining the said compound and an intermediate compound.

EFFECT: novel salt form of a dopamine agonist which has advantages, specifically is not hygroscopic, has a crystalline form and has high melting point is obtained and described.

11 cl, 9 ex, 2 tbl, 6 dwg

FIELD: chemistry.

SUBSTANCE: benzamide derivatives are presented by the formula [1] or its salt, where Z is -O-, -NR5-, -S-, -SO-; 1 is 0 or 1; m is 0 or 1; R1 is hydrogen atom, C1-6-alkyl group, R2 is hydrogen atom, hydroxylic group, C1-6- alkyl group, carboxyl group, C1-6-alkoxycarbonyl group or -CONR10R11, or R2 and R1 together form =O; R3 is hydrogen atom or C1-6-alkyl group; R4 is hydrogen atom or halogen atom; V is direct bond or -(CR21R22)n-; P1 and P2 rings are the same or different, and each is aromatic or saturated carbocyclic group, or 5-10-member saturated or unsaturated heterocyclic group containing 1-3 heteroatoms selected out of N, O, S.

EFFECT: obtainment of compound with excellent inhibition effect on vanilloid receptor type 1 activity, efficiency in treatment of diseases involving vanilloid receptor type 1 activity.

17 cl, 56 tbl, 8 ex

FIELD: chemistry.

SUBSTANCE: present invention relates to phenylalanine derivatives and their pharmaceutically acceptable salts. In formula (1) R11 is a hydroxyl group, an alkoxyl group having 1-6 carbon atoms, which can be substituted with a methoxy group, cycloalkoxyl group having 3-6 carbon atoms, or a benzyloxy group; R12 and R13 each independently represents a hydrogen atom, alkyl group having 1-6 carbon atoms, cycloalkyl group having 3-6 carbon atoms, acetyl group or methyloxycarbonyl group, or N(R12)R13 is a 1-pyrrolidinyl group, 1-piperidinyl group, 4-morpholinyl group; R14 is a methyl group; R1' is a hydrogen atom, fluorine atom; X1 is -CH(R1a)-, -CH(R1a)CH(R1b)-, -CH(R1a)CH(R1b)CH(R1c)-, -N(R1a)CH(R1b)CH(R1c)-, -OCH(R1a)CH(R1b)-, -OCH(R1a)CH(R1b)CH(R1c)- or 1,3-pyrrolidinylene, where R1a, R1b, each independently represents a hydrogen atom or a methyl group, and R1c is a hydrogen atom; Y11 and Y12 represent any of the combinations (CI, Cl), (CI, Me), (CI, F). Invention also relates to phenylalanine derivatives of formulae (2)-(14), given in the formula of invention.

EFFECT: obtaining a pharmaceutical composition having antagonistic effect on α4-integrin, containing a phenylalanine derivative as an active ingredient, a α4-integrin antagonist and a therapeutic agent.

65 cl, 51 tbl, 244 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel compounds of formula

,

where the carbon atom denoted * is in R- or S-configuration; X is a concentrated bicyclic carbocycle or heterocycle selected from a group consisting of benzofuranyl, benzo[b]thiophenyl, benzoisothiazolyl, indazolyl, indolyl, benzooxazolyl, benzothiazolyl, indenyl, indanyl, dihydrobenzocycloheptenyl, naphthyl, tetrahydronaphthyl, quinolinyl, isoquinolinyl, quinoxalinyl, 2H-chromenyl, imidazo[1.2-a]pyridinyl, pyrazolo[1.5-a]pyridinyl, and condensed bicyclic carbocycle or condensed bicyclic heterocycle, optionally substituted with substitutes (1 to 4) which are defined below for R14; R1 is H, C1-C6-alkyl, C3-C6-cyclalkyl, C1-C3-alkyl, substituted OR11, -NR9R10 or -CN; R2 is H, C1-C6-alkyl, or gem-dimethyl; R3 is H, -OR11, C1-C6-alkyl or halogen; R4 is H, halogen, -OR11, -CN, C1-C6-alkyl, C1-C6-alkyl, substituted -NR9R10, C3-C6-cycloalkyl, substituted -NR9R10, C(O)R12; or R4 is morpholinyl, piperidinyl, pyrimidinyl, pyridazinyl, pyrazinyl, pyrrolyl, isoxazolyl, pyrrolidinyl, piperazinyl, 2-oxo-2H-pyridinyl, [1.2.4]triazolo[4.3-a]pyridinyl, 3-oxo-[1.2.4]triazolo[4.3-a]pyridinyl, quinoxalinyl, which are optionally substituted with substitutes (1 to 4) which are defined below for R14; R5 is H or C1-C6-alkyl; R6 is H, C1-C6-alkyl, or -OR11; R7 is H; R8 is H, -OR9, C1-C6-alkyl, -CN; R9 is H or C1-C4-alkyl; R10 is H or C1-C4-alkyl; or R9 and R10 taken together with the nitrogen atom to which they are bonded form morpholine; R11 is H, C1-C4-alkyl; R12 is C1-C6-alkyl; R14 in each case is independently selected from a substitute selected from a group consisting of halogen, -OR11, -NR11R12, C1-C6-alkyl, which is optionally substituted with 1-3 substitutes, in each case independently selected from a group consisting of C1-C3-alkyl, aryl; or to pharmaceutically acceptable salts thereof. The invention also relates to a pharmaceutical composition, to a method of obtaining formula (I) compounds, as well as to a method of treating disorders.

EFFECT: obtaining new biological active compounds having norepinephrine, dopamine and serotonin reuptake selective inhibitory activity.

90 cl, 162 ex, 2 tbl

Mif inhibitors // 2383541

FIELD: chemistry.

SUBSTANCE: there is described compound of formula 1

where R1 represents unsubstituted or substituted (C3-C8)cycloalkyl(C1-C4)alkyl, phenyl(C1-C4)alkyl, (C3-C8)cycloalkyl, phenyl, naphthyl, phenyl condensed with 18-(crown)-6, where substitutes include phenyl, halogen, hydroxy, aminosulfonyloxy, (C1-C4)alkoxy, tri(C1-C6)alkylsilyloxy, halogen(C1-C4)alkyl or halogen(C1-C4)alkoxy, R2 represents hydrogen, hydroxyl, aminosulfonyloxy, (C1-C4)alkoxy, tri(C1-C6)alkylsilyloxy or halogen(C1-C4)alkoxy. Also described is use of the compound for making a medicinal agent and a pharmaceutical composition.

EFFECT: disclosed compounds have macrophage migration inhibitory factor activity (MIF).

8 cl, 1 tbl, 2 ex

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of formula

where R1 is hydrogen, alkyl, cycloalkyl, hydroxy group, hydroxyalkyl, alkoxy group, alkoxyalkyl, aminoalkyl, aryl, heterocyclyl, alkylsulfonyl, alkylsulfanyl, alkylcarbonylalkyl, alkylcarbonyloxyalkyl, aminocarbonylalkyl, heterocyclylcarbonylalkyl, alkoxycarbonylalkyl, alkoxyalkylaminocarbonylalkyl, cycloalkylalkoxyalkyl, arylalkyloxyalkyl, aryloxyalkyl, haloidalkyl, haloidalkoxy group or haloidalkoxyalkyl, R2 is hydrogen, alkyl, cycloalkylalkoxyalkyl, alkoxyalkyl, arylalkoxyalkyl, haloidalkoxyalkyl, pyrrolidyl, morpholinyl, thiomorpholinyl, arylalkyl, arylalkoxy group, aryloxy group or heterocyclylalkyl, R3 is hydrogen or alkyl, R4 is hydrogen, alkyl or haloid, R5 is phenyl, naphthyl, piperidyl or 1,2,3,4-tetrahydroisoquinolinyl optionally substituted with one or more substitutes independently selected from alkyl, cycloalkyl, haloid, alkoxy group, nitro group, trifluoromethyl, trifluoromethoxy group, trifluoromethylcarbonyl group, aryl, aryloxy group, alkoxycarbonylalkoxy group and alkylsulfonyl, R6 is hydrogen or alkyl, and their pharmaceutically acceptable salts and esters, under the condition that N-(6-(1,1-dimethylethyl)-2-pyridinyl)-4-methylbenzenesulfamide is excluded, and in cases when R1 is hydrogen or methyl, R2 is not hydrogen or methyl, as well as a pharceutical composition based on these compounds.

EFFECT: novel chemical compounds which can be used in treating and preventing diabetes, obesity and eating disorders are obtained and described.

15 cl, 192 ex

FIELD: chemistry.

SUBSTANCE: described are compounds of formula ; or their pharmaceutically acceptable salts, where A is phenyl, X is CH2- or C=O; Y is O; k equals 1; m equals 0; R2 and R3 each independently represents hydrogen or alkyl, R4 is a group of formula or . Disclosed compounds have selective affinity to 5-HT6 and 5-HT2A receptors. Also described is a pharmaceutical composition containing said compounds and use of the said compounds in making a medicinal agent for treating diseased conditions of the central nervous system.

EFFECT: more effective treatment.

49 cl, 1 tbl, 16 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel compounds of formula (I) which are protein tyrosine kinase 1B(PTP-1B) inhibitors and can be used in medicinal preparations for treating and preventing diseases related to high concentration of glucose in blood, for example diabetes and obesity. In formula (I) X is a X-1 group or X-2: , where R1 and R2 are each independently selected from a group consisting of hydrogen, lower alkyl, alkoxy-lower alkyl and hydroxyl-lower alkyl, under the condition that, R1 and R2 both represent hydrogen; R3, R4, R6 and R7 are each independently selected from a group consisting of hydrogen, lower alkyl; lower alkyl substituted with halogen or hydroxy; lower alkoxy; lower alkoxy substituted with halogen, hydroxy or lower alkoxy; hydroxyl, halogen, lower alkylthio, lower alkylsufanyl, lower alkylsufanyl, aminosufonyl, cyano, nitro, carbamoyl, lower mono- or dialkylcarbamoyl, lower alkanoyl, benzoyl, phenyl, phenyl substituted with halogen, phenyloxy, lower mono- or dialkylamino, hydroxy-substituted lower alkylamino, lower alkanoylamino, lower alkylsulfonylamino, heterocycloalkyl, hydroxy-substituted heterocycloalkyl, heterocyclyloxy, heterocyclylcarbonyl; where each heterocycloalkyl in the said values represents a 5-6-membr ring containing 1-2 heteroatoms selected from nitrogen and oxygen, and which can be substituted with lower alkyl or phenyl-lower alkyl; carboxyl, lower alkoxycarbonyl and a substitute of formula: ; R8 is selected from a group consisting of hydrogen, lower alkylthio, halogen, alkoxy-lower alkoxy, lower alkoxy, halogen-lower alkyl, hydroxy-lower alkyl; represents a 5-member heteroaromatic ring containing 1 or 2 heteroatoms selected from a group consisting of hydrogen, sulphur and nitrogen; R8 and R9 each independently represents hydrogen or lower alkyl.

EFFECT: novel compounds have useful biological properties.

31 cl, 7 dwg, 152 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a combined product containing compounds of formula (I): where: R1 and R2 represent CF3; R3 and R4 represent fluoro; R5 and R6 represent hydrogen; R7 presents Cl, X represents CR8, where R8 represents Cl; and R9 represents NH2; or its veterinary acceptable salt, and b) doramectin. The invention also relates to an antiparasitic veterinary composition based on the said combined product.

EFFECT: obtaining a combined product which can be used in veterinary for treating parasitic infections in mammals.

4 cl, 1 dwg, 1 tbl, 37 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to substituted bicyclic heterocyclic compounds of the formula (I): their tautomeric forms, stereoisomers, polymorphous forms, pharmaceutically acceptable salts and pharmaceutically acceptable solvates wherein groups R1, R2, R3 and R4, and groups R5 and R6 when they are bound with carbon atom they represent hydrogen, halogen atom, hydroxy-group, alkyl, alkoxy-group; R5 and R6 as a single group or both can represent also an oxo-group when they are bound with carbon atom; when R5 and R6 are bound with nitrogen atom then they represent hydrogen atom, hydroxy-group or such unsubstituted groups as alkyl, alkoxy-group, aralkyl. X means oxygen or sulfur atom; Ar means phenylene, naphthylene or benzofuryl. Proposed compounds can be used against obesity and hypercholesterolemia. Also, the invention describes methods for preparing compounds, pharmaceutical compositions, method for treatment and using compounds proposed.

EFFECT: valuable medicinal properties of compounds and compositions.

52 cl, 77 ex

FIELD: organic chemistry, technology of organic compounds.

SUBSTANCE: invention relates to heterocyclic o-dicarbonitriles. Invention describes heterocyclic o-dicarbonitriles of the general formula: wherein R means the following compounds: . Heterocyclic o-dicarbonitriles can be used for preparing hexazocyclanes-fluorophores as a donor-fragment used for preparing hexazocyclanes-bifluorophores and hexazocyclanes-trifluorophores. Invention provides preparing new compounds possessing valuable properties.

EFFECT: valuable properties of compounds.

2 tbl, 10 ex

FIELD: organic chemistry, chemical technology, medicine, pharmacy.

SUBSTANCE: invention relates to derivatives of aryl carboxylic acids and describes a compound of the formula (I):

, wherein groups R1, R2, R3, R4 and groups R5 and R6 when they are joined to carbon atom can be similar or different and mean hydrogen, halogen atom, hydroxy-group or optionally substituted group taken among alkyl, alkoxy-group, phenyl, carboxylic acid or sulfonic acid; one or both substitutes R5 and R6 can mean oxo-group also if they are joined to carbon atom; if R5 and R are joined to nitrogen atom then they mean hydrogen atom, hydroxy-group or optionally substituted alkyl or benzyl; X means heteroatom taken among oxygen and sulfur atom or NH; Ar means optionally substituted bivalent a single or condensed aromatic or heterocyclic group wherein aromatic ring represents phenyl, naphthyl and heterocyclic group represents furan; R7 means hydrogen, halogen atom, alkoxy-group, alkyl, or it forms a bond with the adjacent group R8; R8 means hydrogen atom, hydroxy-, alkoxy-group, alkyl or optionally substituted benzyl; or R8 forms a bond in common with R7; R9 means hydrogen atom or optionally substituted group taken among alkyl, phenyl or benzyl group; R10 means hydrogen atom or optionally substituted group taken among alkyl, phenyl or benzyl group; Y means oxygen atom or NR12 wherein R12 means hydrogen atom, alkyl or benzyl; R10 and R12 can form in common five- or six-membered cyclic structure comprising carbon atoms that involves optionally one or some heteroatoms taken among oxygen, sulfur or nitrogen atoms; a binding group represented by the formula: -(CH2)n-(O)m- can be joined through nitrogen atom or through carbon atom and wherein n means a whole number from 1 to 4; m means a whole number from 0 to 1 under condition that when a binding group is joined through carbon atom then R5 either R6 represents oxo-group; Y means oxygen atom; R9 doesn't mean hydrogen atom; or its derivatives, analogs, its tautomeric forms, its stereoisomers, its polymorphic forms, its pharmaceutically acceptable salts, its pharmaceutically acceptable solvates. Also, invention describes methods for preparing compounds of the general formula (I), intermediate compounds and methods for their preparing, a pharmaceutical composition eliciting activity with respect to hPPRα, hPPRγ and inhibitory activity with respect to HMG-CoA-reductase and involving compound of the formula (I). Also, invention relates to methods for prophylaxis and treatment of different diseases caused by above said activity, a method for reducing the total cholesterol level and a method for reducing the glucose level. Invention provides preparing new compounds eliciting valuable biological properties.

EFFECT: improved preparing methods, valuable medicinal properties of compounds.

27 cl, 64 ex

The invention relates to a derivative of methotrexate, more specifically, to novel derivatives of methotrexate suitable as an Antirheumatic agent, agent, healing psoriasis, and cancerostatic agent

FIELD: chemistry.

SUBSTANCE: described are compounds of formula ; or their pharmaceutically acceptable salts, where A is phenyl, X is CH2- or C=O; Y is O; k equals 1; m equals 0; R2 and R3 each independently represents hydrogen or alkyl, R4 is a group of formula or . Disclosed compounds have selective affinity to 5-HT6 and 5-HT2A receptors. Also described is a pharmaceutical composition containing said compounds and use of the said compounds in making a medicinal agent for treating diseased conditions of the central nervous system.

EFFECT: more effective treatment.

49 cl, 1 tbl, 16 ex

FIELD: pharmacology.

SUBSTANCE: described are enantiomer-free compounds with a general formula of (1) wherein the R1, R2, R3, R4 and X- residue may have as specified in the invention formula, intermediary compounds, a pharmaceutical composition as well as their application in the capacity of medications intended for respiratory tract diseases treatment.

EFFECT: new enantiomer-free b-agonists, their preparation method and application in the capacity of medications.

11 cl, 5 dwg, 3 tbl, 37 ex

FIELD: medicine.

SUBSTANCE: carboxylic acid compounds are presented by formula (I) where R1 represents (1) hydrogen atom, (2) C1-4alkyl; E represents -CO-; R2 represents (1) halogen atom, (2) C1-6 alkyl, (3) trihalogen methyl; R3 represents (1) halogen atom, (2) C1-6alkyl; R4 represents (1) hydrogen atom; R5 represents (1) C1-6alkyl; represents phenyl; G represents (1) C1-6alkylene; represents 9-12-merous bicyclic heterocycle containing heteroatoms, chosen of 1-4 nitrogen atoms, one or two oxygen atoms; m represents 0 or an integer 1 to 4, n represents 0 or an integer 1 to 4, and i represents 0 or an integer 1 to 11 where R2 can be identical or different provided m is equal to 2 or more, R3 can be identical or different provided n is equal to 2 or more, and R5 can be identical or different provided i is equal to 2 or more; both R12 and R13, independently represent (1) C1-4alkyl, (2) halogen atom, (3) hydroxyl or (4) hydrogen atom, or R12 and R13 together represent (1) oxo or (2) C2-5alkylene and where provided R12 and R13 simultaneously represent hydrogen atom, carboxylic acid compound presented by formula (I), represents a compound chosen from the group including the compounds (1) - (32), listed in cl.1 of the patent claim. Besides the invention concerns a pharmaceutical composition based in the compound of formula I and to application of the compound of formula I for making the pharmaceutical composition.

EFFECT: there are produced new carboxylic acid derivatives with antagonistic activity with respect to DP receptor.

14 cl, 74 ex

FIELD: chemistry.

SUBSTANCE: present invention relates to compounds of formula (I-a), where R1 and R2, each independently, represent -COORA (where RA is hydrogen or C1-8 alkyl), -CONRBSO2RC (where RB is hydrogen or C1-8 alkyl, RC is C1-8 hydrocarbon), -D-R1 is -CO-(CH2)2-R1, -CO-(CH2)3-R1, -CO-(CH2)4-R1 or C1-4alkylene-R1; E is a bond or C1-4alkylene; ring formula represents a 3,4-dihydro-2H-1,4-benzoxazine or 1H-indole ring; V is , where R110 is hydrogen or C1-8 alkyl, and the arrow shows that it is bonded to ring A; the group with formula is a phenyl group, which can contain a group with formula , where ring 2 is a C5-10 mono- or bicyclic aromatic carbocyclic ring, which can be partially or completely saturated, spirobicyclic carbocyclic ring, or a carbocyclic ring bonded by a bridge bond; where W is -O-CH2-, -O-(CH2)2, -O-(CH2)3, -O-(CH2)4, -O-(CH2)5, -CH2-O, -(CH2)2-O-, -(CH2)3-O-, -(CH2)4-O-, -(CH2)5-O-, -O-(CH2)3-O-, -O-(CH2)4-O-, -O-(CH2)5-O-, C1-6 alkylene, its N-oxide, its salt or its solvate. The invention also relates to a pharmaceutical composition based on formula I-a compound and its use.

EFFECT: obtaining new derivatives of benzoxazine and indole, with antagonistic effect on cysLT2 and which are useful for preventing and/or curing respiratory diseases, such as bronchial asthma, chronic obstructive lung diseases.

8 cl, 57 tbl, 261 ex

FIELD: pharmacology.

SUBSTANCE: invention concerns novel compounds of formula (1a), formula (1b), formula (1c) and formula (1d), as well as pharmaceutical composition based on them and their application in medicine obtainment. R1-R4, G, W, X, X1, U, V, a, b are defined in the invention claim.

EFFECT: compound with antagonistic effect on vasopressin V1A receptor.

73 cl, 133 ex

FIELD: chemistry.

SUBSTANCE: invention refers to new compounds of general formula (I) or to its pharmaceutically acceptable salts or to it solvates, where m is equal 0 to 3, X stands for N, Y stands for -SO2-, each R1 independently stands for halogen, C1-C12alkyl, halogen(C1-C12)alkyl, hydroxy(C1-C6)alkyl, R2 stands for aryl or heteroaryl which represents monocyclic radical containing 5 to 12 atoms in a cycle, including one, two or three nitrogen heteroatoms in a cycle optionally substituted with halogen or cyano, each R3 and R4 independently stands for C1-C12alkyl, or R3 and R4 together with carbon atom whereto they are attached, form the cyclic group containing 3-6 atoms in a cycle, and each R5, R6, R7, R8 and R9 stands for hydrogen. Besides, the invention concerns the pharmaceutical composition.

EFFECT: preparation of the new biologically active compounds with antagonistic action to 5-NT6 receptor.

15 cl, 6 ex, 2 tbl

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