Amide derivative and pharmaceutical composition containing said derivative

FIELD: chemistry.

SUBSTANCE: invention relates to a compound of formula (1), in which Ar is a group of formula (Ar-1) or (Ar-2), in which R1 is a halogen, R2 is hydrogen, R3 is hydrogen, R4 is hydrogen, alkyl or alkenyl, X is a nitrogen atom or CH, R5 and R6 are each hydrogen and h equals 1; 1 equals 1 or 2; m equals 1 or 2; n equals 0, 1 or 2; o equals an integer from 0 to 3, under the condition that n and o are equal to 0 at the same time. Values of group A are as given in claim 1 of the invention. Described also is a pharmaceutical composition having agonistic activity with respect to 7 serotonin (5-HT4-receptors), which contains a compound of formula (1) and an agent which stimulates enterokinesis or improves functioning of the alimentary canal, which contains a compound of formula (1) as an active ingredient.

EFFECT: novel compounds are obtained and described, which have strong affinity towards 4 serotonin receptors, which are useful as an agent which stimulates enterokinesis or an agent which improves functioning of the alimentary canal.

28 cl, 233 ex, 29 tbl

 

The text descriptions are given in facsimile form.

1. The compound of formula (1)

in which Ar represents a group of the formula (Ar-1) or (Ar-2)
,
in which R1is a halogen, R2represents hydrogen, R3represents hydrogen, R4represents hydrogen, alkyl or alkenyl, X represents a nitrogen atom or CH, R5and R6each represents hydrogen, and h is 1;
l is 1 or 2;
m is 1 or 2;
n is 0, 1 or 2;
o is an integer from 0 to 3, provided that n and o are not simultaneously equal to 0;
A represents a group selected from the group consisting of groups from (1) to (6);
(1) hydrogen, cyano or formyl;
(2) optionally substituted alkyl;
(3) -COR7, -COOR7, -SO2R7or-CO-COR7,
where R7represents an optionally substituted alkyl, optionally substituted of alkenyl, optionally substituted quinil, optionally substituted cyclo is lcil, optionally substituted cycloalkenyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted monocyclic or bicyclic nonaromatic unsaturated heterocyclyl where heterocyclyl attached to any carbon atom of the heterocycle, or optionally substituted monocyclic or bicyclic saturated heterocyclyl where heterocyclyl attached to any carbon atom of the heterocycle;
(4) -CO-COOR8,
where R8represents alkyl;
(5) -CONR9-OR10,
where R9and R10are the same or different, and each represents
a hydrogen or alkyl; and
(6) -CONR12R13, -CSNR12R13or-SO2NR12R13,
where R12represents hydrogen or any of the groups in R7, R13represents hydrogen, alkyl or alkenyl or R12and R13can connect to each other and together with the neighboring nitrogen atom to form optionally substituted saturated or unsaturated monocyclic nitrogen-containing heterocycle containing 1-3 heteroatoms selected from 1-3 nitrogen atoms or 1 oxygen atom;
provided that, if alkyl, alkenyl or quinil in a or R7is substituted, they are substituted by the same or different 1 to 5 substituents selected from the group consisting of h is of mustiala from (a) to (d):
(a) halogen, cyano, hydroxy, carboxy, amino or carbarnoyl;
(b) -OR14, -COR14, -COOR14, -O-COR14, -NR15-COR14, -NR15-COOR14,
-NR15R16or-CONR15R16,
where R14represents alkyl, optionally substituted by same or different 1 to 5 substituents selected from the group consisting of the following substituents:
(b') hydroxy, carboxy, -OR17and-COOR17where R17represents alkyl;
R15represents hydrogen or alkyl;
R16represents alkyl, or both R15and R16can connect to each other and together with the neighboring nitrogen atom to form optionally substituted saturated or unsaturated monocyclic nitrogen-containing heterocycle containing 1-3 heteroatoms selected from 1-3 nitrogen atoms or 1 oxygen atom;
(c) -R20,
where R20represents an optionally substituted cycloalkyl, optionally substituted cycloalkenyl, optionally substituted monocyclic or bicyclic nonaromatic unsaturated heterocyclyl, optionally substituted monocyclic or bicyclic saturated heterocyclyl; and
(d) -R21,
where R21represents optionally substituted aryl or
optionally substituted heteroaryl;
provided that, if the CEC is alkyl or cycloalkenyl is substituted, they substituted the same or different 1 to 5 substituents selected from the following group (s):
(e) an alkyl, alkoxy or oxo;
provided that, if any of the carbon atoms of the ring are substituted in the monocyclic or bicyclic nonaromatic unsaturated heterocyclyl, monocyclic or bicyclic saturated heterocyclyl or a saturated or unsaturated monocyclic nitrogen-containing heterocyclyl, the carbon atoms substituted by same or different 1 to 5 substituents selected from the above group (s),
provided that, if any of the nitrogen atoms of the ring are substituted, they are substituted by the following substituents groups (f):
(f) alkyl, alkanoyl or alkoxycarbonyl;
provided that, if the aryl or heteroaryl is substituted, they are substituted by the same or different 1 to 5 substituents selected from the group consisting of groups (g) to (i):
(g) halogen, cyano, nitro, hydroxy, carboxy, amino, carbarnoyl, or -(CH2)2-O-;
(h) -R14, -OR14, -COOR14, -O-COR14, -NR15-COR14, -NR15-COOR14, -NR15R16
or-CONR15R16,
where R14, R15and R16have the same meanings as above; and
(i) phenyl or phenoxy, or its pharmaceutically acceptable salt.

2. The compound according to claim 1, in which R1is Soboh is chlorine, bromine or iodine, R4represents alkyl, R5and R6each represents hydrogen, or its pharmaceutically acceptable salt.

3. The compound according to claim 2, in which R4represents methyl, ethyl, propyl or isopropyl, or its pharmaceutically acceptable salt.

4. The compound according to claim 1, in which l is 1 or 2, m is 1 or 2, n is 1 or 2, o is 1 or 2, or its pharmaceutically acceptable salt.

5. The compound according to claim 1, in which R1represents chlorine or bromine, R2and R3represent hydrogen, R4represents methyl or ethyl, R5and R6represent hydrogen, h is 1, l is 1, m is 1, n is 2, o is 1, or its pharmaceutically acceptable salt.

6. The compound according to any one of claims 1 to 5, in which a represents a
(1-1) hydrogen, cyano or formyl, or
(2-1) alkyl or phenylselenenyl alkyl, where phenyl optionally substituted by same or different 1 to 5 substituents selected from the group consisting of halogen, hydroxy, alkyl, alkoxy, amino and carboxy, or its pharmaceutically acceptable salt.

7. The compound according to any one of claims 1 to 5, in which a represents a
(3-1) -COR7a, -COOR7a, -SO2R7aor-CO-COR7a,
where R7arepresents an optionally substituted alkyl, optionally substituted of alkenyl, not necessarily for ewenny quinil, optionally substituted cycloalkyl, optionally substituted cycloalkenyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted monocyclic or bicyclic nonaromatic unsaturated heterocyclyl or optionally substituted monocyclic or bicyclic saturated heterocyclyl;
provided that, if alkyl, alkenyl or quinil in R7ais substituted, they are substituted by 1-5 substituents selected from the group consisting of groups (a-1) to (d-1):
(a-1) halogen, cyano, hydroxy, carboxy, amino or carbarnoyl;
(b-1) -R14a, -COR14a, -COOR14a, -O-COR14a, -NR15a-COR14a, -NR15a-COOR14a, -NR15aR16aor-CONR15aR16a,
where R14arepresents alkyl, R15arepresents hydrogen or alkyl, R16arepresents an alkyl or both R15aand R16acan connect to each other and together with the neighboring nitrogen atom to form a saturated monocyclic nitrogen-containing heterocycle containing 1-3 heteroatoms selected from 1-3 nitrogen atoms, 1 oxygen atom or 1 sulfur atom, and nitrogen atom monocyclic nitrogen-containing heterocycle optionally substituted by alkyl, alkanoyl or alkoxycarbonyl;
(C-1) cycloalkyl, which is optionally substituted by the same or different 1-5 for what estately, selected from alkyl or alkoxy, monocyclic or bicyclic saturated heterocyclyl, in which the carbon atom in the ring optionally substituted by same or different 1 to 5 substituents selected from alkyl or alkoxy, and the nitrogen atom in the ring optionally substituted by alkyl, alkanoyl or alkoxycarbonyl; and
(d-1) -R21a,
where R21arepresents aryl or heteroaryl, optionally substituted by same or different 1 to 5 substituents selected from halogen, hydroxy, carboxy, amino, carbamoyl, cyano, -R14a, -OR14a, -NR15a-COR14aor-NR15aR16awhere-R14a, -R15aand R16ahave the same values, shown above;
provided that if cycloalkyl or cycloalkenyl in R7ais substituted, they are substituted by the same or different 1 to 5 substituents selected from the following substituents (e-1):
(e-1) an alkyl or alkoxy;
provided that, if any of the carbon atoms of the ring are substituted in the optionally substituted monocyclic or bicyclic nonaromatic unsaturated heterocyclyl and optionally substituted monocyclic or bicyclic saturated heterocyclyl in R7athey substituted the same or different 1 to 5 substituents selected from the above substituents (e-1), and if any nitrogen atoms Kohl is a are substituted, they substituted the same or different 1 to 5 substituents selected from the following substituents (f-1):
(f-1) alkyl, alkanoyl or alkoxycarbonyl;
provided that, if the aryl or heteroaryl in R7ais substituted, they are substituted by the same or different 1 to 5 substituents selected from the group consisting of the following groups:
(g-1) halogen, nitro, hydroxy, carboxy, amino, carbarnoyl, or cyano;
(h-1) -R14a, -OR14a, -COOR14a, -O-COR14a, -NR15a-COR14a, -NR15a-COOR14aor-NR15aR16awhere-R14a, -R15aand R16ahave the same meanings which are listed above; and
(i-1) phenyl or phenoxy, or its pharmaceutically acceptable salt.

8. The connection according to claim 7, in which a represents a
(3-2) -SO2R7b,
where R7brepresents alkyl, alkyl, substituted optionally substituted phenyl, or optionally substituted phenyl, provided that when phenyl is substituted, it is substituted by the same or different 1 to 5 substituents selected from the group consisting of halogen, hydroxy, carboxy, amino, carbamoyl, -R14b,
-OR14b, -COOR14band-O-COR14bwhere-R14brepresents alkyl, or its pharmaceutically acceptable salt.

9. The connection of claim 8, in which R7brepresents a C1-3alkyl, or supplied with the ski acceptable salt.

10. The connection according to claim 7, in which a represents a
(3-3) -COR7cor-CO-COR7c,
where R7crepresents an optionally substituted alkyl or optionally substituted of alkenyl;
provided that, if the alkyl or alkenyl in R7cis substituted, they are substituted by 1-5 substituents selected from the group consisting of substituents (a-2) to (d-2):
(a-2) hydroxy, halogen, carbarnoyl, or cyano;
(b-2) -OR14a, -COR14C, -COOR14c, -O-COR14c, -NR15c-COR14c, -NR15cR14cor-CONR15cR16cwhere-R14cand R16care the same or different alkali and R15Crepresents hydrogen or alkyl;
(C-2) cycloalkyl or monocyclic or bicyclic saturated heterocyclyl, where the nitrogen atom monocyclic or bicyclic saturated heterocyclyl optionally substituted by alkyl, alkanoyl or alkoxycarbonyl; and
(d-2) -R21cwhere R21crepresents aryl or heteroaryl and aryl and heteroaryl optionally substituted by same or different 1 to 5 substituents selected from the group consisting of halogen, hydroxy, carboxy, amino, carbamoyl, cyano, -R14cor14cwhere R14chas the same meanings which are listed above; or its pharmaceutically acceptable salt.

11. The connection of claim 10, in which R7cdepict is to place a 1-3alkyl, optionally substituted by a group selected from the group consisting of the following groups (a-3) and (b-3):
(a-3) hydroxy, carbarnoyl, or cyano, and
(b-3) -OR14d-COR14d, -COOR14d, -O-COR14d, -NR15d-COR14d, -NR15dR16dor-CONR15dR16dwhere R14dand R16dare the same or different C1-3alkali and R15drepresents hydrogen or C1-3alkyl or C2-3alkenyl, optionally substituted by a group selected from the group consisting of the above groups (a-3) and (b-3), or its pharmaceutically acceptable salt.

12. The connection according to claim 7, in which a represents a
(3-4) -COR7d,
where R7drepresents an optionally substituted cycloalkyl, optionally substituted cycloalkenyl, optionally substituted monocyclic or bicyclic nonaromatic unsaturated heterocyclyl or optionally substituted monocyclic saturated heterocyclyl;
provided that, if any of the carbon atoms of the ring are substituted, they are substituted by the same or different 1 to 5 substituents selected from alkyl or alkoxy, and, if the nitrogen atoms of the ring are substituted, they are substituted by alkyl, alkanoyl or alkoxycarbonyl, or its pharmaceutically acceptable salt.

13. The connection according to claim 7, in which And represents the t a
(3-5) -COR7e,
where R7erepresents optionally substituted aryl or optionally substituted heteroaryl;
provided that, if the aryl or heteroaryl is substituted, they are substituted by the same or different 1 to 5 substituents selected from the group consisting of the following substituents from (g-2) to (i-2):
(g-2) halogen, amino, carbarnoyl, or cyano;
(h-2) -R14e, -OR14e, -O-COR14e, -NR15e-COR14e, -NR15e-COOR14eor
-NR15eR16ewhere R14eand R16eare the same or different and each represents alkyl, R15erepresents hydrogen or alkyl; and (i-2) phenyl or phenoxy, or its pharmaceutically acceptable salt.

14. The connection according to claim 7, in which a represents a
(3-6) -COOR7f,
where R7frepresents alkyl, alkenyl or optionally substituted phenyl;
with the proviso that when phenyl is substituted, it is substituted by the same or different 1 to 5 substituents selected from the group consisting of halogen, nitro, hydroxy, -R14fand-OR14fwhere R14frepresents alkyl, or its pharmaceutically acceptable salt.

15. The connection 14, in which R7frepresents a C1-3alkyl or C2-3alkenyl, or its pharmaceutically acceptable salt.

16. The compound according to any one of claims 1 to 5, where As before the hat is (6-1) -CONR 12aR13a, -CSNR12aR13aor-SO2NR12aR13awhere R12arepresents hydrogen, C1-3alkyl, C2-3alkenyl, C1-3alkyl, substituted C2-3alkoxycarbonyl,1-3alkyl, substituted optionally substituted phenyl, or optionally substituted phenyl, with the proviso that when phenyl is substituted, it is substituted by the same or different 1 to 5 substituents selected from the group consisting of halogen, nitro, hydroxy, carboxy, amino, carbamoyl,
-R14a, -OR14a, -COOR14aand-O-COR14awhere R14arepresents alkyl;
R13arepresents hydrogen or alkyl, or both R12aand R13acan connect to each other and together with the neighboring nitrogen atom to form optionally substituted saturated or unsaturated 4 to 6 membered monocyclic nitrogen-containing heterocycle containing 1-3 heteroatoms selected from the group consisting of 1-3 nitrogen atoms and 1 oxygen atom, and nitrogen atom monocyclic nitrogen-containing heterocycle optionally substituted by alkyl, alkanoyl or alkoxycarbonyl, or its pharmaceutically acceptable salt.

17. The connection clause 16, in which R12aand R13aare the same or different and each represents a C1-3alkyl;
R12arepresents an optionally substituted is th phenyl, where phenyl optionally substituted by 1 or 2 halogen atoms, hydroxy, carboxy, amino, carbamoyl, -R14a, -OR14a, -COOR14aor-O-COR14awhere R14arepresents alkyl, and R13arepresents hydrogen; or both R12aand R13aare connected to each other and together with the adjacent nitrogen atom form pyrrolidinyl, piperidinyl, morpholinyl or imidazolyl; or its pharmaceutically acceptable salt.

18. The compound according to any one of claims 1 to 5, in which a represents a (5-1)-CONR9a-OR10a,
where R9aand R10aare the same or different and each represents alkyl, or its pharmaceutically acceptable salt.

19. The compound according to claim 1, selected from the group consisting of the following compounds:
4-amino-N-[{4-[(1-(1-azetidinone)-4-piperidinyl)methyl)]-2-morpholinyl}methyl]-5-chloro-2-ethoxybenzene;
4-amino-5-chloro-2-methoxy-N-[{4-[(1-pyrrolidinecarbonyl-4-piperidinyl)methyl]-2-morpholinyl}methyl]benzamide;
4-amino-5-chloro-2-ethoxy-N-[{4-[(1-(1-pyrrolidinecarbonyl)-4-piperidinyl)methyl]-2-morpholinyl}methyl]benzamide;
4-amino-5-chloro-N-[{4-[(1-dimethylcarbamoyl-4-piperidinyl)methyl]-2-morpholinyl}methyl]-2-methoxybenzamide;
4-amino-5-chloro-N-[{4-[(1-dimethylcarbamoyl-4-piperidinyl)methyl]-2-morpholinyl}methyl]-2-ethoxybenzene;
4-amino-5-chloro-N-[{4-[(1-dimethylthiocarbamyl-4-piperidinyl)methyl]-2-morpholinyl}methyl]-2-oxybenzone;
4-amino-5-chloro-N-[{4-[(1-dimethylsulphamoyl-4-piperidinyl)methyl]-2-morpholinyl}methyl]-2-methoxybenzamide;
4-amino-5-chloro-N-[{4-[(1-dimethylsulphamoyl-4-piperidinyl)methyl]-2-morpholinyl}methyl]-2-ethoxybenzene;
4-amino-5-chloro-N-[{4-[(1-dimethylcarbamoyl-4-piperidinyl)methyl]-2-morpholinyl}methyl]-2-isopropoxybenzoic;
4-amino-5-chloro-N-[{4-[(1-diethylcarbamoyl-4-piperidinyl)methyl]-2-morpholinyl} methyl] -2-ethoxybenzene;
4-amino-5-chloro-N-[{4-[(1-diisopropylamino-4-piperidinyl)methyl]-2-morpholinyl}methyl]-2-methoxybenzamide;
6-amino-5-chloro-N-[{4-[(1-dimethylcarbamoyl-4-piperidinyl)methyl]-2-morpholinyl}methyl]-2-methoxypyridine-3-carboxamide;
N-[{4-[(1-allylmethylamine-4-piperidinyl)methyl]-2-morpholinyl}methyl]-4-amino-5-chloro-2-ethoxybenzene;
4-amino-5-chloro-N-[{4-[(1-(1-pyrrolidinecarbonyl-4-piperidinyl)methyl]-2-morpholinyl}methyl]-2,3-dihydrobenzo[b]furan-7-carboxamide;
4-amino-5-chloro-N-[{4-[(1-dimethylcarbamoyl-4-piperidinyl)methyl]-2-morpholinyl}methyl]-2,3-dihydrobenzo[b]furan-7-carboxamide;
4-amino-5-chloro-2-ethoxy-N-[{4-[(1-methylcarbamoyl-4-piperidinyl)methyl]-2-morpholinyl}methyl]benzamide;
4-amino-5-chloro-2-ethoxy-N-[{4-[(1-ethylcarbamate-4-piperidinyl)methyl]-2-morpholinyl}methyl]benzamide;
4-amino-5-chloro-2-methoxy-N-[{4-[(1-phenylcarbamoyl-4-piperidinyl)methyl]-2-morpholinyl}methyl]benzamide;
4-amino-5-chloro-2-methoxy-N-[{4-[(1-(2-methoxyphenyl)carbarnoyl-4-piperidinyl)methyl]2-morpholinyl}methyl]benzamide;
4-amino-5-chloro-2-methoxy-N-[{4-[(1-(3-triptoreline)carbarnoyl-4-piperidinyl)methyl]-2-morpholinyl}methyl]benzamide;
N-[{4-[(1-(3-acetylphenyl)carbarnoyl-4-piperidinyl)methyl]-2-morpholinyl}methyl]-4-amino-5-chloro-2-methoxybenzamide;
4-amino-5-chloro-N-[{4-[(1-(3, 5dimethylphenyl)carbarnoyl-4-piperidinyl)methyl]-2-morpholinyl}methyl]-2-methoxybenzamide;
4-amino-5-chloro-N-[{4-[(1-(3,4-dichlorophenyl)carbarnoyl-4-piperidinyl)methyl]-2-morpholinyl}methyl]-2-methoxybenzamide;
4-amino-N-[{4-[(1-benzylcarbamoyl-4-piperidinyl)methyl]-2-morpholinyl}methyl]-5-chloro-2-methoxybenzamide;
4-amino-5-chloro-2-methoxy-N-[{4-[(1-(2-methylbenzyl)carbarnoyl-4-piperidinyl)methyl]-2-morpholinyl}methyl]benzamide;
4-amino-5-chloro-2-methoxy-N-[{4-[(1-(4-methoxybenzyl)carbarnoyl-4-piperidinyl)methyl]-2-morpholinyl}methyl]benzamide;
4-amino-5-chloro-N-[{4-[(1-(2,4-dichlorobenzyl)carbarnoyl-4-piperidinyl)methyl]-2-morpholinyl}methyl]-2-methoxybenzamide;
4-amino-5-chloro-2-methoxy-N-[{4-[(1-(2-phenethyl)carbarnoyl-4-piperidinyl)methyl]-2-morpholinyl}methyl]benzamide;
4-amino-5-chloro-2-ethoxy-N-[{4-[(1-methoxycarbonyl-4-piperidinyl)methyl]-2-morpholinyl}methyl]benzamide;
4-amino-5-chloro-N-[{4-[(1-methanesulfonyl-4-piperidinyl)methyl]-2-morpholinyl}methyl]-2-methoxybenzamide;
4-amino-5-chloro-2-ethoxy-N-[{4-[(1-methanesulfonyl-4-piperidinyl)methyl]-2-morpholinyl}methyl]benzamide;
4-amino-5-chloro-2-methoxy-N-[{4-[(1-(1-propoxycarbonyl)-4-piperidinyl)methyl]-2-morph linel}methyl]benzamide;
N-[{4-[(1-allyloxycarbonyl-4-piperidinyl)methyl]-2-morpholinyl}methyl]-4-amino-5-chloro-2-methoxybenzamide;
4-amino-5-chloro-N-[{4-[(1-isobutoxide-4-piperidinyl)methyl]-2-morpholinyl}methyl]-2-methoxybenzamide;
4-amino-5-chloro-2-methoxy-N-[{4-[(1-phenoxycarbonyl-4-piperidinyl)methyl]-2-morpholinyl}methyl]benzamide;
4-amino-5-chloro-2-methoxy-N-[{4-[(1-(2-methoxyphenethyl)-4-piperidinyl)methyl]-2-morpholinyl}methyl]benzamide;
N-[{4-[(1-acetoxyacetyl-4-piperidinyl)methyl]-2-morpholinyl}methyl]-4-amino-5-chloro-2-ethoxybenzene;
4-amino-5-chloro-N-[{4-[(1-(1-cyclopentanecarbonyl)-4-piperidinyl)methyl]-2-morpholinyl}methyl]-2-ethoxybenzene;
4-amino-5-chloro-N-[{4-[(1-(2-cyclopropanecarbonyl)-4-piperidinyl)methyl]-2-morpholinyl}methyl]-2-ethoxybenzene;
4-amino-5-chloro-2-ethoxy-N-[{4-[(1-[2-(furan-2-yl)vinylcarbenes]-4-piperidinyl)methyl]-2-morpholinyl}methyl]benzamide;
4-amino-5-chloro-2-ethoxy-N-[{4-[(1-[2-(thiophene-2-yl)vinylcarbenes]-4-piperidinyl)methyl]-2-morpholinyl}methyl]benzamide;
4-amino-N-[{4-[(1-(3-butterball)-4-piperidinyl)methyl]-2-morpholinyl}methyl]-5-chloro-2-ethoxybenzene;
4-amino-5-chloro-2-ethoxy-N-[{4-[(1-(5-hexenkessel)-4-piperidinyl)methyl]-2-morpholinyl}methyl]benzamide;
4-amino-N-[{4-[(1-(1,3-butadienerubber)-4-piperidinyl)methyl]-2-morpholinyl}methyl]-5-chloro-2-ethoxybenzene;
4-amino-5-chloro-2-ethoxy-N-[{4-[(1-(1,5-hexadecanoyl)-4-piperidinyl)methyl]-2-morpholinyl}methyl]b is samida;
4-amino-N-[{4-[(1-[1-(1-propyne)carbonyl]-4-piperidinyl)methyl]-2-morpholinyl}methyl]-5-chloro-2-ethoxybenzene;
4-amino-5-chloro-N-[{4-[(1-methoxycarbonyl-4-piperidinyl)methyl]-2-morpholinyl}methyl]-2,3-dihydrobenzo[b]furan-7-carboxamide;
N-[{4-[(1-acetyl-4-piperidinyl)methyl]-2-morpholinyl}methyl]-4-amino-5-chloro-2,3-dihydrobenzo[b]furan-7-carboxamide;
4-amino-5-chloro-N-[{4-[(1-methanesulfonyl-4-piperidinyl)methyl]-2-morpholinyl}methyl]-2,3-dihydrobenzo[b]furan-7-carboxamide;
4-amino-N-[{4-[(1-benzoyl-4-piperidinyl)methyl]-2-morpholinyl}methyl]-5-chloro-2-ethoxybenzene;
4-amino-5-chloro-N-[{4-[(1-(3-perbenzoic)-4-piperidinyl)methyl]-2-morpholinyl}methyl]-2-methoxybenzamide;
4-amino-5-chloro-2-ethoxy-N-[{4-[(1-(3-perbenzoic)-4-piperidinyl)methyl]-2-morpholinyl}methyl]benzamide;
4-amino-5-chloro-N-[{4-[(1-(4-chlorobenzoyl)-4-piperidinyl)methyl]-2-morpholinyl}methyl]-2-methoxybenzamide;
4-amino-5-chloro-N-[{4-[(1-(4-chlorobenzoyl)-4-piperidinyl)methyl]-2-morpholinyl}methyl]-2-ethoxybenzene;
4-amino-N-[{4-[(1-(3-bromobenzoyl)-4-piperidinyl)methyl]-2-morpholinyl}methyl]-5-chloro-2-methoxybenzamide;
4-amino-5-chloro-2-methoxy-N-[{4-[(1-(2-methylbenzoyl)-4-piperidinyl)methyl]-2-morpholinyl}methyl]benzamide;
4-amino-5-chloro-2-methoxy-N-[{4-[(1-(3-methylbenzoyl)-4-piperidinyl)methyl]-2-morpholinyl}methyl]benzamide;
4-amino-5-chloro-2-methoxy-N-[{4-[(1-(4-methylbenzoyl)-4-piperidinyl)methyl]-2-morpholinyl}methyl]benzamide;
4-amino-5-chloro-2-ethoxy-N-[4-[(1-(4-methylbenzoyl)-4-piperidinyl)methyl]-2-morpholinyl}methyl]benzamide;
4-amino-5-chloro-N-[{4-[(1-(4-ethylbenzoyl)-4-piperidinyl)methyl]-2-morpholinyl}methyl]-2-methoxybenzamide;
4-amino-N-[{4-[(1-(tert-butylbenzoyl)-4-piperidinyl)methyl]-2-morpholinyl}methyl]-5-chloro-2-methoxybenzamide;
4-amino-5-chloro-N-[{4-[(1-(3-hydroxybenzoyl)-4-piperidinyl)methyl]-2-morpholinyl}methyl]-2-methoxybenzamide;
4-amino-5-chloro-N-[{4-[(1-(4-hydroxybenzoyl)-4-piperidinyl)methyl]-2-morpholinyl}methyl]-2-methoxybenzamide;
N-[{4-[(1-(2-acetoxybenzoic)-4-piperidinyl)methyl]-2-morpholinyl}methyl]-4-amino-5-chloro-2-methoxybenzamide;
N-[{4-[(1-(2-acetoxybenzoic)-4-piperidinyl)methyl]-2-morpholinyl}methyl]-4-amino-5-chloro-2-ethoxybenzene;
N-[{4-[(1-(3-acetoxybenzoic)-4-piperidinyl)methyl]-2-morpholinyl}methyl]-4-amino-5-chloro-2-methoxybenzamide;
N-[{4-[(1-(4-acetoxybenzoic)-4-piperidinyl)methyl]-2-morpholinyl}methyl]-4-amino-5-chloro-2-methoxybenzamide;
4-amino-5-chloro-2-methoxy-N-[{4-[(1-(3-methoxybenzoyl)-4-piperidinyl)methyl]-2-morpholinyl}methyl]benzamide;
4-amino-5-chloro-2-methoxy-N-[{4-[(1-(4-methoxybenzoyl)-4-piperidinyl)methyl]-2-morpholinyl}methyl]benzamide;
4-amino-5-chloro-2-ethoxy-N-[{4-[(1-(4-methoxybenzoyl)-4-piperidinyl)methyl]-2-morpholinyl}methyl]benzamide;
4-amino-5-chloro-2-methoxy-N-[{4-[(1-(2-phenoxybenzoyl)-4-piperidinyl)methyl]-2-morpholinyl}methyl]benzamide;
4-amino-5-chloro-N-[{4-[(1-(3-dimethylaminobenzoyl)-4-piperidinyl)methyl]-2-morpholinyl}methyl]-2-methoxybenzamide;
4-amino-5-chloro-N-[{4-[(1-(4-d is methylaminomethyl)-4-piperidinyl)methyl]-2-morpholinyl}methyl]-2-methoxybenzamide;
4-amino-5-chloro-2-methoxy-N-[{4-[(1-(4-methoxycarbonylbenzyl)-4-piperidinyl)methyl]-2-morpholinyl}methyl]benzamide;
4-amino-5-chloro-2-methoxy-N-[{4-[(1-(4-phenylbenzyl)-4-piperidinyl)methyl]-2-morpholinyl}methyl]benzamide;
4-amino-N-[{4-[(1-(4-amino-3-chloroperbenzoic)-4-piperidinyl)methyl]-2-morpholinyl}methyl]-5-chloro-2-methoxybenzamide;
4-amino-5-chloro-N-[{4-[(1-(2-furancarboxylic)-4-piperidinyl)methyl]-2-morpholinyl}methyl]-2-methoxybenzamide;
4-amino-5-chloro-N-[{4-[(1-(1-imidazolidinyl)-4-piperidinyl)methyl]-2-morpholinyl}methyl]-2-methoxybenzamide;
4-amino-5-chloro-N-[{4-[(1-[(1,2-dihydrobenzofuran-7-yl)carbonyl]-4-piperidinyl)methyl]-2-morpholinyl}methyl]-2-methoxybenzamide;
4-amino-5-chloro-2-methoxy-N-[{4-[(1-[(5-methylthiophene-2-yl)carbonyl]-4-piperidinyl)methyl]-2-morpholinyl}methyl]benzamide;
4-amino-5-chloro-2-methoxy-N-[{4-[(1-[(S)-2-tetrahydrofuranyl]-4-piperidinyl)methyl]-2-morpholinyl}methyl]benzamide;
4-amino-5-chloro-2-methoxy-N-[{4-[(1-methoxyacetyl-4-piperidinyl)methyl]-2-morpholinyl}methyl]benzamide;
4-amino-5-chloro-2-ethoxy-N-[{4-[(1-methoxyacetyl-4-piperidinyl}methyl]-2-morpholinyl}methyl]benzamide;
4-amino-5-chloro-N-[{4-[(1-hydroxyacetic-4-piperidinyl)methyl]-2-morpholinyl}methyl]-2-methoxybenzamide;
4-amino-5-chloro-2-ethoxy-N-[{4-[(1-hydroxyacetic-4-piperidinyl)methyl]-2-morpholinyl}methyl]benzamide;
4-amino-5-chloro-N-[{4-[(1-hydroxyacetic-4-piperidinyl)methyl]-2-morpholinyl}methyl]-2,3-dihydro what Enzo[b]furan-7-carboxamide;
4-amino-5-chloro-2-methoxy-N-[{4-[(1-(4-piperidinylcarbonyl)-4-piperidinyl)methyl]-2-morpholinyl}methyl]benzamide;
N-[{4-[(1-acetyl-4-piperidinyl)methyl]-2-morpholinyl}methyl]-4-amino-5-chloro-2-methoxybenzamide;
4-amino-N-[{4-[(1-benzoylbenzoate-4-piperidinyl)methyl]-2-morpholinyl}methyl]-5-chloro-2-methoxybenzamide;
4-amino-5-chloro-N-[{4-[(1-cyanoacetyl-4-piperidinyl)methyl]-2-morpholinyl}methyl]-2-methoxybenzamide;
4-amino-5-chloro-N-{[4-{[1-(3-methoxypropyl)-4-piperidinyl]methyl}-2-morpholinyl]methyl}-2-methoxybenzamide;
4-amino-5-chloro-N-{[4-{[1-((S)-2-methoxypropyl)-4-piperidinyl]methyl}-2-morpholinyl]methyl}-2-methoxybenzamide;
4-amino-5-chloro-2-methoxy-N-{[4-{[1-(3-tetrahydrofuranyl)-4-piperidinyl]methyl}-2-morpholinyl]methyl}benzamide;
4-amino-5-chloro-N-{[4-{[1-(1,2-disopropyl)-4-piperidinyl]methyl}-2-morpholinyl]methyl}-2-methoxybenzamide;
4-amino-5-chloro-2-methoxy-N-{[4-{[1-(4-oxazolidinyl)-4-piperidinyl]methyl}-2-morpholinyl]methyl}benzamide;
4-amino-5-chloro-2-methoxy-N-{[4-{[1-(3-triazolylmethyl)-4-piperidinyl]methyl}-2-morpholinyl]methyl}benzamide;
4-amino-5-chloro-N-{[4-{[1-(4-cyanobenzoyl)-4-piperidinyl]methyl}-2-morpholinyl]methyl}-2-methoxybenzamide;
N-[{4-[(1-acetyl-4-piperidinyl)methyl]-2-morpholinyl}methyl]-4-amino-5-chloro-2,3-dihydrobenzo[b]furan-7-carboxamide;
4-amino-5-chloro-N-{[4-{[1-(3-tetrahydrofuranyl)-4-piperidinyl]methyl}-2-morpholinyl]methyl}-2,3-dihydrobenzo[b]f the RAS-7-carboxamide; and
4-amino-5-chloro-N-[{4-[(1-hydroxyacetic-4-piperidinyl)methyl]-2-morpholinyl}methyl]-2,3-dihydrobenzo[b]furan-7-carboxamide, or their pharmaceutically acceptable salts.

20. The connection according to claim 19, in which the carbon atom at the 2-position of morpholinyl has the S-configuration.

21. (S)-4-amino-5-chloro-N-[{4-[(1-dimethylcarbamoyl-4-piperidinyl)methyl]-2-morpholinyl}methyl]-2-ethoxybenzene.

22. (S)-4-amino-5-chloro-N-[{4-[(1-methanesulfonyl-4-piperidinyl)methyl]-2-morpholinyl}methyl]-2-methoxybenzamide.

23. (S)-4-amino-5-chloro-2-ethoxy-N-[{4-[(1-(methylbenzoyl)-4-piperidinyl)methyl]-2-morpholinyl}methyl]-benzamide.

24. The hydrobromide dihydrate (S)-4-amino-5-chloro-N-[{4-[(1-hydroxyacetic-4-piperidinyl)methyl]-2-morpholinyl}methyl]-2-methoxybenzamide.

25. (S)-4-amino-5-chloro-N-[{4-[(1-((S)-2-methoxypropyl)-4-piperidinyl)methyl]-2-morpholinyl}methyl]-2-methoxybenzamide.

26. Pharmaceutical composition having agonistic activity against receptor 4 serotonin (5-HT4-receptor)containing the compound according to any one of claims 1 to 25 or its pharmaceutically acceptable salt.

27. Agonist receptor 4 serotonin containing as active ingredient a compound according to any one of claims 1 to 25 or its pharmaceutically acceptable salt.

28. Agent, stimulating enterokinase, or an agent that enhances the function of the digestive tract, containing as the active ingredient compounds is their any one of claims 1 to 25 or its pharmaceutically acceptable salt.



 

Same patents:

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to compounds of general formula (I), wherein A represents a pyrrole group or a pyrazole group, and X represents a carbon atom or a nitrogen atom; R1 represents a carboxy group; R2 independently represents a group specified in a substitute group α; R3 independently represents phenyl(C1-C6alkyl)group substituted by, phenyl(C1-C6alkyl)group (wherein the substitute(s) represents (represent) 1-4 groups independently specified in the substitute group α); m is equal to 0, 1, 2 or 3, n is equal to 0 or 1; each of R4, R5, R6 and R7 independently represents a hydrogen atom, C1-C6alkyl group or a halogen atom; B represents a substituted naphthyl group (wherein the substitute(s) represents (represent) 1-4 groups independently specified in the substitute group α), or the group represented by formula (II), wherein B1, B2 and α are those as specified in the patent claim. Also, the invention refers to a pharmaceutical composition possessing lipolysis inhibiting activity, to the use of the compounds of formula (I) in preparing a drug preparation for treating hyperlipidemia, dislipidemia, abnormal lipid metabolism, arteriosclerosis or type II diabetes mellitus and to a method of treating or preventing the mentioned diseases.

EFFECT: preparing the compounds of formula (I) possessing lipolysis inhibiting activity.

36 cl, 1 dwg, 1 tbl, 69 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to compounds of general formula

, wherein X represents a halogen atom or C1-6-alkyl; and has the value of 0, 1, 2 or 3; R1 represents H; R2 represents or ; R3 represents C1-6-alkyl, C3-10-cycloalkyl, phenyl, 6-member heterocycloalkyl representing tetrahydropyranyl, or 5-10-member heteroaryl specified in pyridinyl, pyrazinyl, pyrimidinyl, pyridazinyl, benzo[1,3]dioxolyl and 2,3-dihydrobenzo[1,4]dioxynyl; which be substituted and contains one to five substitutes specified in the patent claim. The invention also refers to pharmaceutical compositions possessing high affinity to dopamine D3 receptor and serotonin 5-HT2A receptor containing said compounds, and the use thereof in preparing drugs.

EFFECT: preparing the compounds of formula (I) possessing high affinity to dopamine D3 receptor and serotonine 5-HT2A receptor.

15 cl, 4 dwg, 5 tbl, 78 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to a phenylpyrazol derivative presented by formula (1) or to its pharmaceutically acceptable salt: wherein R1 and R2, which may be identical or different, each represents C1-C6 alkyl, or R1 and R2 are coupled together with an adjacent nitrogen atom to form a 5-6-merous saturated heterocylic ring (wherein the mentioned saturated heterocylic ring may be substituted by halogen or C1-C6 alkyl), n represents an integer 0 to 2, T represents a hydrogen atom, halogen or C1-C6 alkyl, and R has one of formulas (I)-(V), (VII) or (VIII):

(wherein Z1 and Z2, which may be identical or different, each represents -CH2-, -O- or -NR11-, p represents an integer 0 to 3, q represents an integer 0 to 1, r and s which may be identical or different, which represents an integer 0 to 2, R3 represents halogen, C1-C6 alkyl, or hydroxy, R4 and R5 which may be identical or different, each represents a hydrogen atom, C1-C6 alkyl (wherein said C1-C6 alkyl may be substituted by hydroxy, hydroxy- C1-C6 alkoxy, C2-C7 alkoxycarbonyl or carboxy), or formula -(CH2)m-Ar1 (wherein Ar1 represents wherein (wherein said phenyl is substituted by halogen or C1-C6 alkyl), and m represents an integer 0 to 1), R6 represents oxo, R7 represents a hydrogen atom or C1-C6 alkyl, R8 represents C1-C6 alkyl (wherein said C1-C6 alkyl may be substituted by halogen), C1-C6 alkoxy (wherein said C1-C6 alkoxy is substituted by halogen) or formula -(CH2)1-Ar2 (wherein Ar2 represents phenyl (wherein said phenyl is substituted by C1-C6 alkoxy, hydroxyl or cyano) or pyridinyl, and 1 represents an integer O to 1), G represents -CO- or -SO2-, R9 represents C1-C6 alkyl, C1-C6 alkoxy, phenyl (wherein said phenyl may be substituted by halogen or pyridinyl, and R11 represents C1-C6 alkyl)}.

EFFECT: there are produced new compounds and a preventive or therapeutic agent on the basis of said compounds which can find application in medicine for treating dementia, Alzheimer's disease, attention deficit/hyperactivity disorder, schizophrenia, epilepsy, convulsions of central genesis, eating behaviour disorders, obesity, diabetes, hyperlipidemia, sleep disturbances, narcolepsy, sleeping apnoea syndrome, circadian rhythm disorder, depression or allergic rhinitis.

12 cl, 3 tbl, 72 ex

FIELD: chemistry.

SUBSTANCE: invention relates to substituted N-phenyl-bipyrrolidine ureas of formula (I) ,

where values of R, R1, R2, R3, R4 and R5 are given in claim 1.

EFFECT: compounds are capable of binding with the H3 receptor, which enables use thereof to prepare a pharmaceutical composition and for diseases associated with the central nervous system.

10 cl, 36 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to compounds of formula

wherein m is equal to 0, 1, 2; n is equal to 0, 1, 2, 3; each p, s, t is equal to 0 or 1; X represents CHR8 wherein R8 represents hydrogen; represents -CR9=C<, and then a dash line represents a bond, R9 independently represents hydrogen or C1-6-alkyl, or wherein R9 together with one of R2 or R20 forms a direct bond; R1 represents hydrogen; R2 and R20 are specified in: halogen, cyano, polyhalogen-C1-6-alkyl, C1-6-alkyl, morpholinyl, C1-6-alkyloxy with any of said groups is optionally and independently substituted by hydroxy, NR21R22 wherein R21 and R22 are independently specified in hydrogen, C1-6-alkylcarbonyl; or R2 and R20 together with a phenyl cycle whereto attached form a naphthaline group; or one of R2 or R20 have the values specified above, and the other of R2 or R20 together with R9 form a direct bond; R3 represents hydrogen; R4 and R5 independently represent hydrogen, C1-6-alkyl, hydroxy-C1-6-alkyl, C2-6-alkenyl or C1-6-alkyloxy; or R6 represents hydrogen; when p is equal to 1, then R7 represents hydrogen; Z represents one of the radicals presented in the patent claim. Also, the invention refers to a based pharmaceutical composition, using the compounds of formula (I) for producing the drug preparation for treating the disorders medicated by p53-MDM2 interaction for treating cancer, and to methods for producing the compounds of formula (I).

EFFECT: preparing the compounds of formula (I) as p53-MDM2 interaction inhibitors.

13 cl, 5 tbl, 31 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to particular compounds, which demonstrate inhibiting activity with respect to ERK, whose structure formula is given in description, to their pharmaceutically acceptable salts, based on them pharmaceutical composition and their application for treatment of cancer, mediated by ERK activity.

EFFECT: obtaining compounds, which demonstrate inhibiting activity with respect to ERK.

5 cl

FIELD: chemistry.

SUBSTANCE: invention relates to a method of producing heterocycle-substituted pyridine derivatives of general formula (I) by reacting a compound of general formula (III) with a compound of formula (II) in a solvent and in the presence of a catalyst based on palladium or a base, where R1, R2, X, Y, Q, A, Z, R, R3 and R4 are described in the claim.

EFFECT: method enables to obtain pyridine derivatives on an industrial scale.

7 cl, 27 ex

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of formula (I) or pharmaceutically acceptable salts thereof, where Q is phenyl or pyridinyl; A is pyrazolyl or triazolyl, where each A is independently additionally unsubstituted or substituted with 1 or 2 substitutes represented by Ra, or A is formula (a); Va is C(R4), Vb is N or C(R5) and Vc is N; or Va is N, Vb is C(R5) and Vc is N or C(R6); R4 is hydrogen, R5 is hydrogen, C1-6alkyl, -ORb, -SRb, aryl, selected from phenyl, heteroaryl, selected from thienyl, or cycloalkyl, selected from cyclopropyl; R6 is hydrogen or aryl, selected from phenyl; R7 is hydrogen or C1-6alkyl; R3 is hydrogen, C1-3alkyl, -OH, -S(O)2R1, or heteroaryl, selected from tetrazolyl, where the heteroaryl is bonded to a nitrogen atom through a ring carbon atom; Rb, Rx, Ry, Rza, Rzb, Rw, Re, Rk, Rm, Rn, Rq and R1, in each case, are independently hydrogen, C1-3alkyl or C1-3haloalkyl; and Rf, in each case, is independently hydrogen, C1-3alkyl or -OH (the rest of the substitutes assume values given in the claim). The invention also relates to a pharmaceutical composition, having inhibiting action on DGAT-1, which contains a compound of formula (I), and a treatment method.

EFFECT: compounds of formula (I) as DGAT-1 inhibitors are provided.

16 cl, 9 dwg, 1 tbl, 127 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to new pyrimidine derivatives and their pharmaceutically acceptable salts possessing the properties of a mTOR kinase inhibitor. In formula (I): A represents a 6-8-member mono- or bicyclic heterocyclic ring containing 1 to 2 heteroatoms optionally specified in N and O as apexes of the ring and having 0-2 double bonds; and wherein the ring A is additionally substituted by 0 to 2 substitutes RA specified in a group consisting of -ORa, -Rc and -(CH2)1-4-ORa wherein Ra is optionally specified in hydrogen and C1-6alkyl; Rc represents C1-6alkyl; G is specified in a group consisting of -C(O)-, -OC(O)-, -NHC(O)- and -S(O)0-2-; B is specified in a group consisting of phenylene and 5-6-member heteroarylene consisting 1-2 nitrogen heteroatom as apexes of the ring, and substituted by 0 to 1 substitutes RB specified in F, Cl, Br, I and Rp; wherein Rp represents C1-6 alkyl; D is specified in a group consisting of -NR3C(O)NR4R5, -NR4R5, C(O)NR4R5, -NR3C(=N-CN)NR4R5, -NR3C(O)R4, -NR3C(O)OR4 and -NR3S(O)2R4, and wherein the group D and a substitute placed on an adjoining atom in the ring B, optionally combined to form a 5-6-member heterocyclic or heteroaryl ring containing 1 to 3 heteroatoms specified in N, O and S, as apexes of the ring and substituted by the substitute 0-1 RD. The R1-R5 radical values are presented in the patent claim.

EFFECT: invention also refers to a pharmaceutical composition containing said compounds, and to the use of the compounds for preparing a drug for treating a malignant tumour mediated by mTOR kinase activity.

33 cl, 13 dwg, 4 tbl, 498 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to new antibacterial compounds of formula I

wherein R1 represents halogen or alkoxy group; each U and W represents N; V represents CH, and R2 represents H or F, or each U and V represents CH; W represents N, and R2 represents H or F, or U represents N; V represents CH; W represents CH or CRa, and R2 represents H, or also when W represents CH, may represent F; Ra represents CH2OH or alkoxycarbonyl; A represents group CH=CH-B, a binuclear heterocyclic system D, phenyl group which is mono-substituted in the position 4 by C1-4 alkyl group, or phenyl group which is di-substituted in positions 3 and 4 wherein each of two substitutes is optionally specified in a group consisting of C1-4 alkyl and halogen; B represents mono- or di-substituted phenyl group wherein each substitute is a halogen atom; D represents group

wherein Z represents CH or N, and Q represents O or S; or to salts of such compounds.

EFFECT: compounds are used for treating bacterial infections.

13 cl, 2 tbl, 25 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to isoxazole derivatives of formula

and their pharmaceutically acceptable salts wherein X-Y is N-O or O-N; R1 is independently specified in a group consisting of halogen and C1-4alkyl; or two substitutes R1 together with carbon atoms whereto attached form a 6-member aromatic cycle; R2 represents hydroxy-C1-8alkyl; a is equal to 1, each of m and n is independently equal to 0, 1 or 2. Also, the invention refers to a pharmaceutical composition possessing type 1 11β-hydroxysteroid dehydrogenase inhibitory activity and containing the compounds of formula (I), to the use of the mentioned compounds for producing a drug preparation for treating or preventing glaucoma, as well as to a method of treating glaucoma.

EFFECT: compounds of formula (I) as type 1 11β-hydroxysteroid dehydrogenase inhibitors.

9 cl, 2 dwg, 28 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to 7-substituted indoles of formula I:

or their pharmaceutically acceptable salts wherein the values A1, B1, C1, D1, E1, F1, G1, L are presented in cl. 1 of the patent claim.

EFFECT: compounds inhibit activity of anti-apoptotic protein Mc1-1 that enables using them in pharmaceutical compositions.

5 cl, 7 dwg, 2 tbl, 609 ex

FIELD: chemistry.

SUBSTANCE: invention relates phenyl pyrrole derivatives formula (I) where: A denotes =NOR4, O; R4 denotes, C1-C6 alkyl; R1 denotes C1-C6 alkyl, C1-C6 alkoxy, halogen-C1-C6 alkyl, halogen-C1-C6 alkoxy, NH2, mono- C1-C6 alkylamino, halogen-mono-C1-C6 alkylamino, di(C1-C6 alkyl)amino, halogen-di-(C1-C6 alkyl)amino; or A and R1 together with the carbon atom with which they are bonded form a 5- or 6-member heterocyclic aromatic group or a heterocyclic group with partially or completely reduced saturation, which can be benzo-condensed, can contain 1-3 heteroatoms selected from N, O and S, which can be substituted and contain 1 or 2 α substitutes; R2 denotes phenyl which can be substituted with 1 or 2 α substitutes, or a 6-member heteroaryl group containing 1 or 2 N atoms, which can be substituted with 1 or 2 α substitutes; R3 denotes OH, C1-C6 alkoxy, values of α are given in claim 1, or a pharmaceutically acceptable salt thereof.

EFFECT: compounds exhibit glucokinase activating activity, which enables use thereof in treating diabetes.

51 cl, 1 tbl, 132 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a compound of formula or a pharmaceutically acceptable salt thereof, in which R1 denotes hydrogen or C1-6alkyl; R2 denotes isooxazolyl group, substituted with C1-6alkyl; RB denotes -CF3, -CHF2, -CH2F, or C1-6alkyl. The invention also relates to pharmaceutical compositions for treating cancer which contain the disclosed compounds.

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

15 cl, 77 dwg, 10 tbl, 13 ex

FIELD: chemistry.

SUBSTANCE: in general formula 1 , a cyclic ring can be selectively formed; each of R1 and R2 is independently selected from a group consisting of hydrogen, with a straight or branched alkyl chain having 1-6 carbon atoms and phenetyl or R1 and R2 together form a 5- or 6-member heterocyclic ring or R1 and R2 together with Ar1 form a bicyclic ring; Ar1 is selected from a group consisting of furanyl, thionyl, methylene dioxyphenyl and phenyl, which can be substituted with at least one identical or different substitutes selected from a group consisting of hydrogen, with a straight or branched alkyl chain having 1-6 carbon atoms, a halogen such as F, O and Br, with a straight or branched alkoxy chain, having 1-6 carbon atoms, nitro and trifluoromethyl; Z is hydrogen or fluorine, or taken together with Ar1 forms a bicyclic ring; Ar2 is selected from a group consisting of phenyl, methylene dioxyphenyl, pyridine pyrimidine, naphthyl, bis(fluorophenyl)methyl and quinoxaline, which can be substituted with at least one identical or different substitutes selected from a group consisting of hydrogen, with a straight or branched alkyl chain, having 1-6 carbon atoms, hydroxy, halogen, with a straight or branched alkoxy chain having 1-6 carbon atoms, nitro, acetyl, tert-butyl acetate, trifluoromethyl, amino and acetate; n is equal to 1 or 2; m is an integer from 0 to 2.

EFFECT: improved method.

26 cl, 2 dwg, 2 tbl, 87 ex

FIELD: chemistry.

SUBSTANCE: invention is a 6-10-member aryl selected from phenyl, naphthyl, tetrahydronaphthalenyl, indanyl or a 6-member heteroaryl containing 1-2 N atoms, selected from pyridyl or pyrimidinyl, where the aryl and heteroaryl groups can be unsubstituted or substituted with 1-3 substitutes selected from a group consisting of C3-6-cycloalkyl, phenyl, phenyloxy, benzyl, benzyloxy, halogen atom, C1-7-alkyl, C1-7-alkoxy, oxazolyl, piperidin-1-yl, or C1-7-alkyl, substituted with a halogen atom, or represents phenyl, where at least one hydrogen atom is substituted with deuterium or tritium; R2 is a hydrogen atom, C1-7-alkyl or is benzyl, unsubstituted or substituted C1-7-alkoxy or halogen atom; or R1 and R2 together with a N atom with which they are bonded form 2,3-dihydroindol-1-yl or 3,4-dihydro-1quinolin-1-yl. The invention also relates to a method of producing compounds of formula and to a pharmaceutical composition having high affinity for the TAAR1 receptor.

EFFECT: compounds of formula (I), having high affinity for the TAAR1 receptor.

29 cl, 4 dwg, 1 tbl, 183 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to new substituted heteroaryl derivatives of general formula I: , wherein: A means N, CR7-10, with A at the most twice meaning N; W means O, S or NR4, the values B, C, R7-10 are presented in clause 1 of the patent claim. The method for preparing the compound I is described.

EFFECT: compounds show analgesic activity that enables using them for a variety of diseases, especially acute pain, neuropathic, chronic or inflammatory pain.

16 cl, 2 tbl, 307 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: present invention refers to new imidazole derivatives of formula I wherein R1 represents a hydrogen atom or C1-7alkyl; R2 represents C1-7alkyl; R3 represents C1-7alkyl, C1-7alkoxy, phenyloxy, benzyloxy, a halogen atom or C1-7alkyl substituted by a halogen atom; R4 represents a hydrogen atom or C1-7alkyl; X represents -CH2-, -CHR2 - or -O; Y represents -CH2-, -CH2CH2- or a bond; provided X represents -O-, Y represents -CH2-; Z represents -CH2- or -CHR2-; provided R2 is found twice, simultaneously for X and Z which are CHR2 , then R2 can be identical alkyls or different; n has the value 0, 1 or 2; provided n has the value 2, R3 can be identical or different; and its pharmaceutically acceptable acid addition salts, except for the following compounds: 1-(1H-imidazol-4-ylmethyl)-1,2,3,4-tetrahydro-quinoline and 1-(3H-imidazol-4-ylmethyl)-2,3-dihydro-1H-indole. Also, the invention refers to a method for preparing the compounds of formula I, to a drug based on the compound of formula I and applying the compound of formula I in preparing the drug.

EFFECT: there are prepared new imidazole derivatives effective in treating such pathological conditions, as bipolar disorder, stress-induced disorder, psychotic disorders, schizophrenia, neurological conditions, Parkinson's disease, neurodegenerative disorders, Alzheimer's disease.

13 cl, 61 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to a compound of formula (II)

or to its pharmaceutically acceptable salt wherein the ring A represents a group presented by formula 2 R1 represents hydrogen or C1-6alkyl; R2 represents -SR5, halogen, halogenated C1-6alkyl, etc., R3 represents a group presented by formula: -CH=CH-C(RaRb)-Rc-Rd, or a group presented by formula: -(CReRf)m-C(RaRb)-Rc-Rd wherein radicals and symbols have the values presented in the patent claim, R4 represents -OR6, -CONR7R8, -NR9CONR7R8, -(CR10R11)POH, -(CR10R11)pOCONR7R8, -NR9COR12, -(CR10R11)pNR9COR12, -C(=O)NR9OR12, -CONR9CONR7R8, -CN, halogen or NR9(C=O)OR12; R5 represents C1-6alkyl; R6 represents -CONR7R8; each of R7 and R8 independently represents hydrogen or etc., R10 and R11 independently represents hydrogen; R12 represents C1-6alkyl; each of m and p independently represents an integer 1 to 3. This compound is applicable as a type 1 11β-hydroxysteroiddehydrogenase inhibitor.

EFFECT: invention also refers to single compounds, pharmaceutical compositions on the basis of the declared compounds, to a method for preventing and treating diabetes and the use of the compound of formula (II).

21 cl, 289 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a novel clathrate complex of β-cyclodextrin with 1-{[6-bromo-1-methyl-5-methoxy-2-phehylthiomethyl-1-H-indol-3-yl]carbonyl}-4-benzylpiperazine of formula : with molar ratio 1-{[6-bromo-1-methyl-5-methoxy-2-phehylthiomethyl-1-H-indol-3-yl]carbonyl}-4-benzylpiperazine: β-cyclodextrin from 1:1 to 1:10, synthesis method and use thereof as an antiviral agent for treating influenza. The disclosed method involves mixing solutions of β-cyclodextrin and 1-{[6-bromo-1-methyl-5-methoxy-2-phehylthiomethyl-1-H-indol-3-yl]carbonyl}-4-benzylpiperazine in molar ratio from 1:1 to 1:10 while stirring and heating to temperature not higher than 70°C and then maintaining said conditions until a homogeneous solution is obtained and extraction of the obtained complex.

EFFECT: clathrate complex is a novel effective anti-influenza virus agent which is obtained using a novel efficient method.

13 cl, 2 ex, 3 tbl, 11 dwg

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to a new lipid compound of general formula , wherein n=0; R1 and R2 are identical or different, and may be specified in a group of substitutes consisting of a hydrogen atom, a C1-C7alkyl group, a halogen atom and a C1-C7alkoxy group; X represents COR3 or CH2OR4, wherein R3 is specified in a group consisting of hydrogen, hydroxy, C1-C7alkoxy and amino; and R4 is specified in a group consisting of hydrogen, C1-C7alkyl or C1-C7acyl, Y represents C9-C21 alkene with one or more double bonds in E- or Z-configurations with the chain Y being unsubstituted and containing a double bond in the ω-3 position; provided R1 and R2 cannot simultaneously represent a hydrogen atom.

EFFECT: invention refers to pharmaceutical compositions containing the lipid compounds which are used for treating and/or preventing the conditions related to high NFkB functions, treating and/or preventing an inflammatory disease or a condition, lower plasma insulin and/or blood glucose levels, treating insulin resistance, treating and/or preventing peripheral tissue insulin resistance and/or diabetic condition, eg type 2 diabetes mellitus.

45 cl, 1 tbl, 1 dwg, 31 ex

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