Tetrazole compounds and use thereof as antagonists of metabotropic glutamate receptor

FIELD: chemistry.

SUBSTANCE: present invention relates to a tetrazole compound with general formula I , where X3 and X4 are independently N and C, where one of X3 and X4 is certainly C; P is phenyl; m equals 1 or 2, where if m equals 1, R1 is bonded to P through a carbon atom on ring P in the meta-position of ring P relative the point at which P is bonded to X3, and if m equals 2, R1 is bonded to P through a carbon atom on ring P in positions 2 and 5 of ring P; R1 is halogen, C1-6alkyl, OC1-6alkyl or cyano group; X1 is C2-3alkyl, C2-3alkenyl, NR3, O, S, CR3R4, SO, SO2; X2 is a bond, CR3R4, O, S, NR3, SO, SO2; R3 and R4 are independently chosen from a group which consists of hydrogen, hydroxy, C1-6alkyl; Q is triazolyl, piperazinyl, or triazole or imidazole ring, condensed with a 6- or 7-member heterocyclic ring with one or two N atoms as heteroatoms; R is C1-6alkyl, C3-6cycloalkyl, pyridinyl, which can be substituted with a nitro, cyano, halogen or OC1-4alkyl group; phenyl, which can be substituted with a halogen, C1-4alkyl, OC1-4alkyl group; (CO)OC1-4alkyl; pyrimidinyl, which can be substituted with a OC1-4alkyl group; p equals 0, 1 or 2, or pharmaceutically acceptable salt or hydrate thereof.

EFFECT: invention also relates to method of inhibiting activity of mGluR5 receptors.

11 cl, 44 ex

 

The text descriptions are given in facsimile form.

1. Tetrazole compound of General formula I

where X3and X4independently represent N and s, and one of X3and X4necessarily represent;
P represents phenyl;
m is 1 or 2, and
if m is equal to 1, then R1connected to P via a carbon atom on the ring R in the meta-position of the ring relative to the point P joining P with X3and if m is equal to 2, then R1attached to R through carbon atoms on the ring P in positions 2 and 5 ring P;
R1represents halogeno, C1-6alkyl, OC1-6alkyl or cyano;
X1selected from the group consisting of C2-3of alkyl, C2-3alkenyl, NR3, O, S, CR3R4, SO, SO2;
X2selected from the group consisting of ties, CR3R4, O, S, NR3 , SO, SO2;
R3and R4independently selected from the group consisting of hydrogen, hydroxy, C1-6of alkyl;
Q represents triazolyl, piperazinil, or triazole or imidazole ring condensed with a 6 - or 7-membered heterocyclic ring with one or two N atoms as heteroatoms;
R2represents a C1-6alkyl, C3-6cycloalkyl, pyridinyl which can be substituted by nitro, cyano, halogeno or group OC1-4alkyl; phenyl which may be substituted, halogen, C1-4the alkyl group OC1-4alkyl; (CO)OC1-4alkyl; pyrimidinyl, which may be substituted by a group OC1-4alkyl;
p is 0, 1 or 2, or its pharmaceutically acceptable salt or hydrate.

2. The compound according to claim 1, where X3represents N and X4is a C.

3. The compound according to claim 1, where R1selected from Cl, F, cyano and methyl.

4. The compound according to claim 1, where X1represents CR3R4.

5. The compound according to claim 4, where X2selected from CR3R4, O, S and NR.

6. The compound according to claim 1, where Q is a triazole.

7. The compound according to claim 1, where X2that is the link.

8. The compound according to claim 1, where Q is a piperazinil.

9. The compound according to claim 1, chosen from:
ethyl-4-{[2-(3-chlorophenyl)-2H-tetrazol-5-yl]methyl}piperazine-1-carboxylate,
ethanol is about ester 4-[2-(5-chloro-2-fluoro-phenyl)-2H-tetrazol-5-ylmethyl]-piperazine-1-carboxylic acid,
ethyl ester of 4-(2-meta-tolyl-2H-tetrazol-5-ylmethyl)-piperazine-1-carboxylic acid,
ethyl ester 4-[2-(3-iodine-phenyl)-2H-tetrazol-5-ylmethyl]-piperazine-1-carboxylic acid,
ethyl ester 4-[2-(3-cyano-phenyl)-2H-tetrazol-5-ylmethyl]-piperazine-1-carboxylic acid,
ethyl ester 4-[2-(2-fluoro-5-methyl-phenyl)-2H-tetrazol-5-ylmethyl]-piperazine-1-carboxylic acid,
4-[5-({[2-(3-chlorophenyl)-2H-tetrazol-5-yl]methyl}thio)-4-cyclopropyl-4H-1,2,4-triazole-3-yl]pyridine,
4-[5-({1-[2-(3-chlorophenyl)-2H-tetrazol-5-yl]ethyl}thio)-4-cyclopropyl-4H-1,2,4-triazole-3-yl]pyridine,
ethyl-4-{1-[2-(3-chlorophenyl)-2H-tetrazol-5-yl]ethyl}piperazine-1-carboxylate,
4-{5-[2-(5-chloro-2-fluoro-phenyl)-2H-tetrazol-5-elmersolver]-4-methyl-4H-[1,2,4]triazole-3-yl}-pyridine,
4-{5-[2-(5-chloro-2-fluoro-phenyl)-2H-tetrazol-5-elmersolver]-4-cyclopropyl-4H-[1,2,4]triazole-3-yl}-pyridine,
4-(5-{1-[2-(5-chloro-2-fluoro-phenyl)-2H-tetrazol-5-yl]-ethylsulfanyl}-4-methyl-4H-[1,2,4]triazole-3-yl)-pyridine,
4-(5-{1-[2-(5-chloro-2-fluoro-phenyl)-2H-tetrazol-5-yl]-ethylsulfanyl}-4-cyclopropyl-4H-[1,2,4]triazole-3-yl)-pyridine,
ethyl ester of 4-{1-[2-(5-chloro-2-fluoro-phenyl)-2H-tetrazol-5-yl]-ethyl}-piperazine-1-carboxylic acid,
4-[4-cyclopropyl-5-(2-meta-tolyl-2H-tetrazol-5-elmersolver)-4H-[1,2,4]triazole-3-yl]-pyridine,
4-{4-cyclopropyl-5-[1-(2-meta-tolyl-2H-tetrazol-5-yl)-ethylsulfanyl]-4H-[1,2,4]triazole-3-yl}-pyridine,
4-{4-methyl-5-[1-(2-meta-tolyl-2H-tetrazol-5-yl)-e is ylsulphonyl]-4H-[1,2,4]triazole-3-yl}-pyridine,
3-[5-(4-cyclopropyl-5-pyridin-4-yl-4H-[1,2,4]triazole-3-ylsulphonyl)-tetrazol-2-yl]-benzonitrile,
3-{5-[1-(4-cyclopropyl-5-pyridin-4-yl-4H-[1,2,4]triazole-3-ylsulphonyl)-ethyl]-tetrazol-2-yl}-benzonitrile,
3-{5-[1-(4-methyl-5-pyridin-4-yl-4H-[1,2,4]triazole-3-ylsulphonyl)-ethyl]-tetrazol-2-yl}-benzonitrile,
4-{4-cyclopropyl-5-[2-(2-fluoro-5-methyl-phenyl)-2H-tetrazol-5-elmersolver]-4H-[1,2,4]triazole-3-yl}-pyridine,
4-(4-cyclopropyl-5-{1-[2-(2-fluoro-5-methyl-phenyl)-2H-tetrazol-5-yl]-ethylsulfanyl}-4H-[1,2,4]triazole-3-yl)-pyridine,
4-(5-{1-[2-(2-fluoro-5-methyl-phenyl)-2H-tetrazol-5-yl]-ethylsulfanyl}-4-methyl-4H-[1,2,4]triazole-3-yl)-pyridine,
methyl-(4-methyl-5-pyridin-4-yl-4H-[1,2,4]triazole-3-yl)-(2-meta-tolyl-2H-tetrazol-5-ylmethyl)-amine,
methyl-(4-methyl-5-pyridin-4-yl-4H-[1,2,4]triazole-3-yl)-[1-(2-meta-tolyl-2H-tetrazol-5-yl)-ethyl]-amine,
[2-(3-chloro-phenyl)-2H-tetrazol-5-ylmethyl]-methyl-(4-methyl-5-pyridin-4-yl-4H-[1,2,4]triazole-3-yl)-amine,
{1-[2-(3-chloro-phenyl)-2H-tetrazol-5-yl]-ethyl}-methyl-(4-methyl-5-pyridin-4-yl-4H-[1,2,4]triazole-3-yl)-amine,
[2-(2-fluoro-5-methyl-phenyl)-2H-tetrazol-5-ylmethyl]-methyl-(4-methyl-5-pyridin-4-yl-4H-[1,2,4]triazole-3-yl)-amine,
{1-[2-(2-fluoro-5-methyl-phenyl)-2H-tetrazol-5-yl]-ethyl}-methyl-(4-methyl-5-pyridin-4-yl-4H-[1,2,4]triazole-3-yl)-amine,
[2-(3-iodine-phenyl)-2H-tetrazol-5-ylmethyl]-methyl-(4-methyl-5-pyridin-4-yl-4H-[1,2,4]triazole-3-yl)-amine,
{1-[2-(3-iodine-phenyl)-2H-tetrazol-5-yl]-ethyl}-methyl-(4-methyl-5-pyridin-4-yl-4H-[1,2,4]triazole-3-yl)-and the ina,
methyl-(4-methyl-5-pyridin-4-yl-4H-[1,2,4]triazole-3-yl)-(2-meta-tolyl-2H-tetrazol-5-ylmethyl)-amine,
methyl-(4-methyl-5-pyridin-4-yl-4H-[1,2,4]triazole-3-yl)-[1-(2-meta-tolyl-2H-tetrazol-5-yl)-ethyl]-amine,
[2-(3-chloro-phenyl)-2H-tetrazol-5-ylmethyl]-methyl-(4-methyl-5-pyridin-4-yl-4H-[1,2,4]triazole-3-yl)-amine,
{1-[2-(3-chloro-phenyl)-2H-tetrazol-5-yl]-ethyl}-methyl-(4-methyl-5-pyridin-4-yl-4H-[1,2,4]triazole-3-yl)-amine,
[2-(2-fluoro-5-methyl-phenyl)-2H-tetrazol-5-ylmethyl]-methyl-(4-methyl-5-pyridin-4-yl-4H-[1,2,4]triazole-3-yl)-amine,
{1-[2-(2-fluoro-5-methyl-phenyl)-2H-tetrazol-5-yl]-ethyl}-methyl-(4-methyl-5-pyridin-4-yl-4H-[1,2,4]triazole-3-yl)-amine,
8-[2-(3-iodine-phenyl)-2H-tetrazol-5-ylmethyl]-3-pyridin-4-yl-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyrimidine,
8-{1-[2-(3-iodine-phenyl)-2H-tetrazol-5-yl]-ethyl]-3-pyridin-4-yl-5,6,7,8-tetrahydro-[1,2,4]triazolo [4,3-a] pyrimidine,
3-pyridin-4-yl-8-(2-meta-tolyl-2H-tetrazol-5-ylmethyl)-5,6,7,8-tetrahydro-4H-1,2,3A,8-tetraaza-azulene,
3-pyridin-4-yl-8-[1-(2-meta-tolyl-2H-tetrazol-5-yl)-ethyl]-5,6,7,8-tetrahydro-4H-1,2,3A,8-tetraaza-azulene,
8-[2-(3-chloro-phenyl)-2H-tetrazol-5-ylmethyl]-3-pyridin-4-yl-5,6,7,8-tetrahydro-4H-1,2,3A,8-tetraaza-azulene,
8-{1-[2-(3-chloro-phenyl)-2H-tetrazol-5-yl]-ethyl}-3-pyridin-4-yl-5,6,7,8-tetrahydro-4H-1,2,3A,8-tetraaza-azulene,
8-[2-(2-fluoro-5-methyl-phenyl)-2H-tetrazol-5-ylmethyl]-3-pyridin-4-yl-5,6,7,8-tetrahydro-4H-1,2,3A,8-tetraaza-azulene,
8-{1-[2-(2-fluoro-5-methyl-phenyl)-2H-tetrazol-5-yl]-ethyl}-3-pyridin-4-yl-5,6,7,8-tetrahydro-4H-,2,3A,8-tetraaza-azulene,
8-[2-(3-iodine-phenyl)-2H-tetrazol-5-ylmethyl]-3-pyridin-4-yl-5,6,7,8-tetrahydro-4H-1,2,3A,8-tetraaza-azulene,
8-{1-[2-(3-iodine-phenyl)-2H-tetrazol-5-yl]-ethyl}-3-pyridin-4-yl-5,6,7,8-tetrahydro-4H-1,2,3A,8-tetraaza-azulene,
4-(5-{[2-(3-chlorophenyl)-2H-tetrazol-5-yl]methoxy}-4-methyl-4H-1,2,4-triazole-3-yl)pyridine,
4-(5-{1-[2-(3-chlorophenyl)-2H-tetrazol-5-yl]ethoxy}-4-methyl-4H-1,2,4-triazole-3-yl)pyridine,
4-[4-methyl-5-(2-meta-tolyl-2H-tetrazol-5-ylethoxy)-4H-[1,2,4]triazole-3-yl]-pyridine,
4- {4-methyl-5-[1-(2-meta-tolyl-2H-tetrazol-5-yl)-ethoxy]-4H-[1,2,4]triazole-3-yl}-pyridine,
4{5-[2-(2-fluoro-5-methyl-phenyl)-2H-tetrazol-5-ylethoxy]-4-methyl-4H-[1,2,4]triazole-3-yl}-pyridine,
4-(5-{1-[2-(2-fluoro-5-methyl-phenyl)-2H-tetrazol-5-yl]-ethoxy}-4-methyl-4H-[1,2,4]triazole-3-yl)-pyridine,
4-{5-[2-(3-chloro-phenyl)-2H-tetrazol-5-ylethoxy]-4-cyclopropyl-4H-[1,2,4]triazole-3-yl}-pyridine,
4-(5-{1-[2-(3-chloro-phenyl)-2H-tetrazol-5-yl]-ethoxy}-4-cyclopropyl-4H-[1,2,4]triazole-3-yl)-pyridine,
4-(4-cyclopropyl-5-(2-meta-tolyl-2H-tetrazol-5-ylethoxy)-4H-[1,2,4]triazole-3-yl]-pyridine,
4-{4-cyclopropyl-5-[1-(2-meta-tolyl-2H-tetrazol-5-yl)-ethoxy]-4H-[1,2,4]triazole-3-yl}-pyridine,
4-{4-cyclopropyl-5-[2-(2-fluoro-5-methyl-phenyl)-2H-tetrazol-5-ylethoxy]-4H-[1,2,4]triazole-3-yl}-pyridine,
4-(4-cyclopropyl-5-{1-[2-(2-fluoro-5-methyl-phenyl)-2H-tetrazol-5-yl]-ethoxy}-4H-[1,2,4]triazole-3-yl)-pyridine,
4-{5-[2-(3-iodine-phenyl)-2H-tetrazol-5-ylethoxy]-4-methyl-4H-[1,2,4]triazole-3-yl}-pyridine,
4-(5-{1-[2-(3-iodine-phenyl)-2H-tetraz is l-5-yl]-ethoxy}-4-methyl-4H-[1,2,4]triazole-3-yl)-pyridine,
4-{4-cyclopropyl-5-[2-(3-iodine-phenyl)-2H-tetrazol-5-ylethoxy]-4H-[1,2,4]triazole-3-yl}-pyridine,
4-(4-cyclopropyl-5-{1-[2-(3-iodine-phenyl)-2H-tetrazol-5-yl]-ethoxy}-4H-[1,2,4]triazole-3-yl)-pyridine,
3-[5-(4-methyl-5-pyridin-4-yl-4H-[1,2,4]triazole-3-intoximeter)-tetrazol-2-yl]-benzonitrile,
3-{5-[1-(4-methyl-5-pyridin-4-yl-4H-[1,2,4]triazole-3-yloxy)-ethyl]-tetrazol-2-yl}-benzonitrile,
3-[5-(4-cyclopropyl-5-pyridin-4-yl-4H-[1,2,4]triazole-3-intoximeter)-tetrazol-2-yl]-benzonitrile,
3-{5-[1-(4-cyclopropyl-5-pyridin-4-yl-4H-[1,2,4]triazole-3-yloxy)-ethyl]-tetrazol-2-yl}-benzonitrile,
3-(5{[methyl-(4-methyl-5-pyridin-4-yl-4H-[1,2,4]triazole-3-yl)-amino]-methyl}-tetrazol-2-yl)-benzonitrile,
3-(5-{1-[methyl-(4-methyl-5-pyridin-4-yl-4H-[1,2,4]triazole-3 - yl)-amino]-ethyl}-tetrazol-2-yl)-benzonitrile,
3-[5-(3-pyridin-4-yl-6,7-dihydro-5H-[1,2,4]triazolo[4,3-a]pyrimidine-8-ylmethyl)-tetrazol-2-yl]-benzonitrile,
3-{5-[1-(3-pyridin-4-yl-6,7-dihydro-5H-[1,2,4]triazolo[4,3-a]pyrimidine-8-yl)-ethyl]-tetrazol-2-yl}-benzonitrile,
3-[5-(3-pyridin-4-yl-4,5,6,7-tetrahydro-1,2,3A,8-tetraaza-azulene-8-ylmethyl)-tetrazol-2-yl]-benzonitrile,
3-{5-[1-(3-pyridin-4-yl-4,5,6,7-tetrahydro-1,2,3A,8-tetraaza-azulene-8-yl)-ethyl]-tetrazol-2-yl}-benzonitrile,
(R)- and (S)-4-(5-{1-[2-(3-chlorophenyl)-2H-tetrazol-5-yl]ethoxy}-4-methyl-4H-1,2,4-triazole-3-yl)pyridine,
hydrobromide of 2-(3-chloro-phenyl)-5-[(triphenyl)-λ5-Fontanil)-methyl]-2H-tetrazole,
4-(5-{2-[2-(3-chloro-phenyl)-2H-tetrazol-5-yl]-vinyl}-4-ethyl-4H-[1,2,4]Tr is the azole-3-yl)-pyridine,
4-(5-{2-[2-(3-chloro-phenyl)-2H-tetrazol-5-yl]-vinyl}-4-ethyl-4H-[1,2,4]triazole-3-yl)-pyridine,
1-[2-(3-chloro-phenyl)-2H-tetrazol-5-yl]-2-(4-cyclopropyl-5-pyridin-4-yl-4H-[1,2,4]triazole-3-yl)-ethanol,
2-[2-(3-chloro-phenyl)-2H-tetrazol-5-yl]-1-(4-cyclopropyl-5-pyridin-4-yl-4H-[1,2,4]triazole-3-yl)-ethanol,
4-(5-{2-[2-(3-chloro-phenyl)-2H-tetrazol-5-yl]-vinyl}-4-ethyl-4H-[1,2,4]triazole-3-yl)-pyridine,
3-[4-methyl-5-({[2-(3-were)-2H-tetrazol-5-yl]methyl}thio)-4H-1,2,4-triazole-3-yl]benzonitrile,
5-({[5-(3,5-differenl)-4-ethyl-4H-1,2,4-triazole-3-yl]thio}methyl)-2-(3-were)-2H-tetrazole,
3-[4-methyl-5-({1-[2-(3-were)-2H-tetrazol-5-yl]ethyl}thio)-4H-1,2,4-triazole-3-yl]benzonitrile,
5-(1-{[5-(3,5-differenl)-4-ethyl-4H-1,2,4-triazole-3-yl]thio}ethyl)-2-(3-were)-2H-tetrazole,
6-(4-{1-[2-(3-chlorophenyl)-2H-tetrazol-5-yl]ethyl}piperazine-1-yl)-nicotinanilide,
3-(4-{1-[2-(3-chlorophenyl)-2H-tetrazol-5-yl]ethyl}piperazine-1-yl)pyrazin-2-carbonitrile,
2-(4-{1-[2-(3-chlorophenyl)-2H-tetrazol-5-yl]ethyl}piperazine-1-yl)nicotinanilide,
1 {1-[2-(3-chlorophenyl)-2H-tetrazol-5-yl]ethyl}-4-(3-nitropyridine-2-yl)piperazine,
8-{1-[2-(3-chlorophenyl)-2H-tetrazol-5-yl]ethyl}-3-(3,5-differenl)-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyrimidine,
8-{1-[2-(3-chlorophenyl)-2H-tetrazol-5-yl]ethyl}-3-(4-methoxyphenyl)-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyrimidine,
3-(2-chloro-6-methoxypyridine-4-yl)-8-{1-[2-(3-chlorophenyl)-2H-tetrazol-5-yl]ethyl}-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyrimidine,
8-{1-[2-(3-chlorophenyl)2H-tetrazol-5-yl]ethyl}-3-(2-methoxypyridine-4-yl)-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyrimidine,
8-{[2-(3-chlorophenyl)-2H-tetrazol-5-yl]methyl}-3-(2-methoxypyridine-4-yl)-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyrimidine,
3-(5-{[3-(2-methoxypyridine-4-yl)-6,7-dihydro[1,2,4]triazolo[4,3-a]pyrimidine-8(5H)-yl]methyl}-2H-tetrazol-2-yl)benzonitrile,
3-(2-methoxypyridine-4-yl)-8-{1-[2-(3-itfinal)-2H-tetrazol-5-yl]ethyl}-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyrimidine,
3-(5-{1-[3-(2-methoxypyridine-4-yl)-6,7-dihydro[1,2,4]triazolo[4,3-a]pyrimidine-8(5H)-yl]ethyl}-2H-tetrazol-2-yl)benzonitrile,
3-(5-{[3-(2-methoxypyridine-4-yl)-5,6,7,8-tetrahydro-N-[1,2,4]triazolo[4,3-a][1,3]diazepin-9-yl]methyl}-2H-tetrazol-2-yl)benzonitrile,
3-(5-{[3-(2,6-dimethoxypyrimidine-4-yl)-6,7-dihydro[1,2,4]triazolo[4,3-a]pyrimidine-8(5H)-yl]methyl}-2H-tetrazol-2-yl)benzonitrile,
(R)-3-(5-{1-[3-(2-methoxypyridine-4-yl)-6,7-dihydro[1,2,4]triazolo[4,3-a]pyrimidine-8(5H)-yl]ethyl}-2H-tetrazol-2-yl)benzonitrile,
(S)-3-(5-{1-[3-(2-methoxypyridine-4-yl)-6,7-dihydro[1,2,4]triazolo[4,3-a]pyrimidine-8(5H)-yl]ethyl}-2H-tetrazol-2-yl)benzonitrile,
(R)-ethyl-4-{1-[2-(3-chlorophenyl)-2H-tetrazol-5-yl]ethyl}piperazine-1-carboxylate,
(S)-ethyl-4{1-[2-(3-chlorophenyl)-2H-tetrazol-5-yl]ethyl}piperazine-1-carboxylate,
(R)-ethyl-4-{1-[2-(5-chloro-2-forfinal)-2H-tetrazol-5-yl]ethyl}piperazine-1-carboxylate,
(S)-ethyl-4-{1-[2-(5-chloro-2-forfinal)-2H-tetrazol-5-yl]ethyl}piperazine-1-carboxylate,
(R)-6-(4-{1-[2-(3-chlorophenyl)-2H-tetrazol-5-yl]ethyl}piperazine-1-yl)nicotinanilide,
(S)-6-(4-{1-[2-(3-chlorophenyl)-2H-tetrazol-5-yl]ethyl}Pieper is Zin-1-yl)nicotinanilide,
(R)-3-(4-{1-[2-(3-chlorophenyl)-2H-tetrazol-5-yl]ethyl}piperazine-1-yl)pyrazin-2-carbonitrile,
(S)-3-(4-{1-[2-(3-chlorophenyl)-2H-tetrazol-5-yl]ethyl}piperazine-1-yl)pyrazin-2-carbonitrile,
4-(5-{(S)-1-[2-(3-chloro-phenyl)-2H-tetrazol-5-yl]-ethoxy}-4-methyl-4H-[1,2,4]triazole-3-yl)-pyridine,
2-(3-chloro-phenyl)-5-{(R)-1-[5-(3,5-debtor-phenyl)-4-methyl-4H-[1,2,4]triazole-3-yloxy]-ethyl}-2H-tetrazole,
3-(5-{(R)-1-[2-(3-chloro-phenyl)-2H-tetrazol-5-yl]-ethoxy}-4-methyl-4H-[1,2,4]triazole-3-yl)-pyridine,
4-(5-{2-[5-(3-chlorophenyl)-2H-tetrazol-2-yl]propyl}-4-methyl-4H-1,2,4-triazole-3-yl)-pyridine,
4-(5-{(R)-1-[2-(3-chloro-phenyl)-2H-tetrazol-5-yl]-ethoxy}-4-methyl-4H-[1,2,4]triazole-3-yl)-pyridine,
2-(3-chlorophenyl)-5-[1-methyl-2-phenylphenyl]-2H-tetrazole and
2-({1-[2-(3-chlorophenyl)-2H-tetrazol-5-yl]ethyl}thio)-imidazo[4,5-b]pyridine.

10. The compound according to any one of claims 1 to 9 for use in the treatment of disorders mediated by mGluR5.

11. Method of inhibiting activation of mGluR5 receptors, including the processing of cells containing the indicated receptor, an effective amount of a compound according to any one of claims 1 to 9.



 

Same patents:

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: pharmacology.

SUBSTANCE: invention concerns compounds of the formula and other compounds listed in cl. 1 of invention claim, and pharmaceutical composition based on them, as well as method of mGluR5 receptor activity inhibition involving claimed compounds.

EFFECT: application in treatment and prevention of diseases mediated by mGluR5 receptor activity.

4 cl, 18 dwg, 1009 ex

FIELD: medicine.

SUBSTANCE: according to the invention there is provided substituted indolequinoxalines of the formula (I), where R1 represents hydrogen or represents one or more similar or different substituent in positions from 7 to 10, selected of the group of halogen, low alkyl/alkoxy, hydroxy, triflouromethyl, trichloromethyl, triflouromethoxy, R2 represents similar or different C1-C4 alkyl substituents, X represents CO or CH2, Y represents OH, NH2, NH-(CH2)n-R3, where R3 represents low alkyl, OH, NH2, NHR4 or NR5R6, where R4, R5 and R6 represent low alkyl or cycloalkyl independently and n represents integer from 2 to 4 provided that X represents CH2, Y represents OH or NH-(CH2)n-OH and its pharmaceutically acceptable salt. There is also provided pharmaceutical composition, containing these compounds, methods of compound producing, formula (I).

EFFECT: compounds are applied as medicine for treatment and prevention of autoimmune diseases.

15 cl, 1 ex, 5 dwg

FIELD: chemistry.

SUBSTANCE: invention relates to antagonists of serotonin 5-HT6 receptors - substituted 4-sulphonylpyrazoles and 3-sulphonyl-pyrazolo[1,5-a]pyrimidines of general formula 1 or general formula 1.2. These compounds can be used for treating and preventing development of different cognitive and neurodegenerative diseases of the central nervous system. In general formulae 1 and 1.2, 1 1.2 respectively, Ar is optionally substituted phenyl or optionally substituted 5-6-member heteroaryl, containing a nitrogen, oxygen or sulphur atom as a heteroatom; R1 is a hydrogen atom, optionally substituted C1-C5 alkyl, lower acyl or optionally substituted phenyl; R2 is an optionally substituted amino group or substituted hydroxy group or R1, together with the nitrogen atom to which it is bonded, and R2, together with the carbon atom to which it is bonded, form a substituted pyrimidine ring; R3 is a hydrogen atom, optionally substituted C1-C5alkyl, substituted hydroxyl group or substituted sulphanyl group, R5 is a hydrogen atom, optionally substituted C1-C5alkyl, substituted hydroxyl group or substituted sulphanyl group, R7 and R9 independently represent a hydrogen atom, C1-C3alkyl or phenyl, R8 is a hydrogen atom.

EFFECT: new compounds have useful biological properties.

13 cl, 2 dwg, 4 tbl, 7 ex

FIELD: medicine.

SUBSTANCE: new derivative of diaminopyrroloquinazolines of formula (I) and their pharmaceutically acceptable salts possess properties of proteintyrosine posphatase PTP1 inhibitors which can be used for treating the diseases mediated by action of the latter, particularly for decreasing glucose content in blood. In formula (I) , A stands for 6-membered aromatic ring, or 5- or 6-membered aromatic ring which contains 1 or 2 heteroatoms chosen from S, N and O; R1 is specified from the group including the following radicals: C1-6alkyl, hydroxyC1-6alkyl, mono- or dihydroxy-substituted C1-6alkyl, phenyl-(C1-6alkyl), benzyloxyC1-6alkyl and phenyl-(C1-6alkoxy)C1-6alkyl; R2 is specified from the group including the following radicals: hydrogen, C1-6alkyl, hydroxyC1-6alkyl, mono- or dihydroxy-substituted C1-6alkyl, phenyl-(C1-6alkyl) and phenyl-(C1-6alkoxy)C1-6alkyl; R3 represents hydrogen or methyl; Ra is specified from the group including the following radicals: hydrogen, C1-6alkyl, C1-6alkoxy, hydroxyC1-6alkyl, mono- or dihydroxy-substituted C1-6alkyl, phenyl(C1-6alkyl), benzyloxyC1-6alkyl or ; R10 represents hydrogen or ; x and y separately stand for integers 0 to 4; Rb and Rc are separately specified from the group including the following radicals: hydrogen, C1-6alkyl, perfluorochemical C1-6alkyl, substituted C1-6alkyl, C1-6alkoxy, phenoxy, halogen, (unsubstituted C1-6alkyl)-(substituted phenyl)-(C1-6alkyl), phenyl-(C1-6alkoxy) or ; R11 represents hydrogen, phenyl or unsubstituted C1-6alkyl; p stands for integer 0 to 1; Rd represents hydrogen, substituted C1-6alkyl or perfluorochemical C1-6alkyl; Re represents hydrogen, halogen, substituted C1-6alkyl and perfluorochemical C1-6alkyl; Rf represents hydrogen or C1-6alkyl; the substitutes found in alkyl groups are independently specified from the following groups: hydroxy, C1-6alkoxy, C1-6alkanoyl; and the substitutes found in substituted phenyl as Rb and Rc, are independently specified from the following groups: C1-6alkyl, C1-6alkoxy, hydroxyC1-6alkyl, hydroxyl, hydroxylC1-6alkoxy, halogen, perfluorC1-6alkyl and C1-6alkanoyl.

EFFECT: improved properties of the derivatives.

29 cl, 2 dwg, 48 ex

FIELD: medicine.

SUBSTANCE: invention covers new pyrrolopyrimidine and pyrrolotriazine derivatives substituted with carbamoyl group of formula [I], characterised as a CRF (corticotrophin release factor) receptor antagonist. The compounds can be effective as a therapeutic or preventive agent for such diseases, as depression, anxiety, Alzheimer's disease, Parkinson's disease, etc. in formula [I]: E means N or CR10; R1 means -OR4, -S(O)1R4 or-NR4R5; R2 means hydrogen, C1-6alkyl; R3 means hydrogen; R4 and R5 are identical or different, and independently mean hydrogen, C1-9alkyl, di(C3-7cycloalkyl)-C1-6alkyl, C1-6alkoxy-C1-6alkyl, di(C1-6alkoxy)-C1-6alkyl, hydroxy-C1-6alkyl, cyano-C1-6alkyl, carbamoyl-C1-6alkyl or di(C1-6alkyl)amino-C2-6alkyl, or R4 and R5 together form (CH2)m-A-(CH2)n where A means CHR9; R9 means hydrogen, hydroxy-C1-6alkyl, or cyano-C1-6alkyl; R10 means hydrogen; I means an integer 0, 1 and 2; m means an integer 1, 2, 3 and 4; n means an integer 0, 1, 2 and 3; Ar means phenyl, and specified phenyl is substituted by one or more substitutes being identical or different, and chosen from the group consisting of halogen, C1-6alkyl, trifluoromethyl; their individual isomers or pharmaceutically acceptable salts.

EFFECT: extended application.

9 cl, 2 dwg, 2 tbl, 2 ex

FIELD: medicine.

SUBSTANCE: invention refers to new compounds of formula I where R1 stands for phenyl; G stands for C1-C7-alkylene; Q stands for -NH-; and X stands for C1-C7- alkylene, or to its salts. In addition, the invention concerns a pharmaceutical composition, to application of compound of formula I as defined in claims 1-5 item, as well as the method for making the compound of formula I.

EFFECT: production of the new biologically active compounds inhibiting protein tyrosine kinase.

8 cl, 3 ex

FIELD: medicine.

SUBSTANCE: invention refers to new pyridine derivatives or to their pharmaceutically acceptable salts of general formula 1: wherein R1, R2, R3, R4, R5, R6 and R7 are independently chosen from the group including hydrogen atom, halogen, amino, C1-C6lower alkyl, C2-C6lower alkenyl, C1-C6lower alkoxy, C1-C10alkylamino, C4-C9cycloalkylamino, C4-C9heterocycloalkylamino, C1-C10aralkylamino, arylamino, acylamino, saturated heterocyclyl, acyloxy, aryl, heteroaryl, C1-C10aralkyl, aryloxy; X represents oxygen or sulphur atom; Y represents oxygen atom or N-R8, wherein R8 is chosen from the group including hydrogen atom; aforesaid aryl group is chosen from phenyl, naphthyl and condensed phenyl group; aforesaid heteroaryl and saturated heterocyclic groups represent pentagonal or hexagonal heterocyclic ring containing 1 to 2 heteroatoms chosen from oxygen, nitrogen and sulphur atom; or condensed heterocyclic ring; and aforesaid aryl and heteroaryl groups are those that 1 to 4 assistants chosen from group including halogen, C1-C6lower alkyl, C1-C6lower alkoxy are substituted. And specified compounds or their pharmaceutically acceptable salt of formula 1 are not compounds as follows 6-methyl-3,4-dihydro-pyrano[3,4-c]pyridin-1-one, 5-vinyl-3,4-dihydro-pyrano[3,4-c]pyridin-1-one, 6-methyl-8-furan-2-yl-3,4- dihydropyrano[3,4-c]pyridin-1-one, 3-tert-butyl-5,6,7,8-tetrahydro-[2,7]naphthyridine-8-one and dimethyl ether (3S)-6,8-dimethyl-1-oxo-1,2,3,4-tetrahydro-[2,7]naphthyridine-3,5-dicarboxylic acids.

EFFECT: compounds possess inhibitory action with respect to formation of cytokines involved in inflammatory reactions, can be used as a therapeutic agent for treatment of inflammatory diseases, immune diseases, chronic inflammations; it provides antiinflammatory and analgesic action.

21 cl, 7 tbl, 144 ex

FIELD: chemistry.

SUBSTANCE: described is novel application of 2-methylthio-5-methyl-6-nitro-1,2,4-triazolo[1,5-a]pyrimidin-7(3H)-on. Substance possesses anti-viral activity with respect to flue A (H5N1) virus, West Nile virus and other viral infections. Wide-spectrum anti-viral activity is discovered for the first time.

EFFECT: obtaining anti-viral substance with wide spectrum of action.

1 cl, 8 tbl, 4 ex

FIELD: chemistry.

SUBSTANCE: claimed invention relates to novel derivatives of 2,6-dihydro-7H- pyrazolo[3,4-d]pyradazin-7-one, 1,4-dihydropyrazolo[3,4-b]thiazin-5(6H)-one; N-acylated 4-imidazo[1,2-a]pyridin-2-yl- and 4-imidazo[1,2-a]pyrimidin-2-yl- anilines; amides of [(4H-thieno[3,2-b]pyrrol-5-yl)carbonyl]pyperidin-4-carboxylic acid; amides of 2-(4-carbamoylpyperidin-1-yl)isonicotinic acid; amides of N-sulfonyl-1,2,3,4-tetrahydrochinolin-6-carboxylic acid; as well as to N-acylated 3-azolyl derivatives of 2-amino-4,5,6,7-tetrahydtithieno[2,3-c]pyridine possessing properties of Hh-signal cascade inhibitors.

EFFECT: compounds can be applied for use in pharmaceutical compositions and medications for treating diseases induced by abberant activity of Hedgehog (Hh) signal system, in particular, oncological diseases, for instance, for pancreatic carcinoma treatment.

23 cl, 13 dwg, 11 tbl, 26 ex

FIELD: pharmacology.

SUBSTANCE: invention concerns indazol derivatives of general formulae (I) or (II) , where radicals and groups are defined as shown in cl. 1 of invention claim, and their pharmaceutically acceptable salts. Also invention claims medicine, method of medicine obtainment and application of claimed compounds in treatment and/or prevention of fatty acid metabolism derangement and glucose assimilation disorders.

EFFECT: inhibition of hormone-sensitive lipases.

13 cl, 1 tbl, 103 ex

FIELD: chemistry.

SUBSTANCE: invention relates to new a compound of formula I or formula II, or to its pharmaceutically acceptable salts, I II, where X is S; R1 is H or C1-C6alkyl; R2 is NR5R6; R3 is aryl, substituted with a halogen; R4 is H; R5 is H; R6 is H; R7 is CH2NR8R9 where R8 is H, C1-C10alkyl, C3-C8cycloalkyl, aryl, aryl(C1-C6alkyl), aryl(C2-C6alkenyl), heterocycle(C1-C6alkyl), heterocycle(C2-C6alkenyl), hydroxyl(C1-C6alkyl), hydroxyl(C2-C6alkyl), C1-C6alkoxycarbonyl, aryl(C1-C6alkoxy)carbonyl, carbamoyl(C1-C6alkyl); where the above mentioned aryl is an aromatic ring and is not substituted or substituted with one to three substituting groups, each of which, independently from the others, is chosen from: methylenedioxy, hydroxy, C1-C6-alkoxy, halogen, C1-C6alkyl, trifluoromethyl, trifluoromethoxy, NO2, NH2, NH(C1-C6alkyl), N(C1-C6alkyl)2, NH-acyl, N(C1-C6alkyl)-acyl, hydroxy(C1-C6alkyl), dihydroxy(C1-C6alkyl), CN, C(=O)O(C1-C6alkyl), phenyl, phenyl(C1-C6alkyl), phenyl(C1-C6alkenyl), phenoxy and phenyl(C1-C6alkoxy), R9 is H, C1-C10alkyl, heterocycle(C1-C6alkyl) or heterocycle(C2-C6alkenyl); where the above mentioned heterocycle represents a 5-member saturated monocyclic ring system, consisting of carbon atoms, as well as heteroatoms, chosen from a group comprising N, O, and S, which can be unsubstituted or have one to three substituting groups, independently chosen from a list which includes NO2, aryl(C1-C6alkyl), arylsulphonyl; or R8 and R9 together with nitrogen, to which they are bonded, form a heterocycle, which represents a 5 - 7-member saturated monocyclic ring system, consisting of carbon atoms, as well as one to three heteroatoms, chosen from a group comprising N, O and S, which can be unsubstituted or have one to three substituting groups, independently chosen from a list which includes C1-C6alkoxy, hydroxy, C1-C6alkyl, C2-C6-alkenyl, C(=O)O(C1-C6alkyl), C(=O)NH2, C(=O)NH(C1-C6alkyl), C(=O)N(C1-C6-alkyl)2, hydroxy(C1-C6alkyl), dihydroxy(C2-C6alkyl), aryl, aryl(C1-C6alkyl), aryl(C2-C6alkenyl), aryl(C1-C6alkoxy) and pyrimidin-2-yl; and m equals 0. The invention also relates to a pharmaceutical composition, as well as to use of formula I or formula II compounds.

EFFECT: obtaining new biologically active compounds, with inhibitory properties towards casein kinase 1ε.

32 cl, 3 tbl

FIELD: medicine.

SUBSTANCE: invention covers new compounds of formula (I) where: one of groups R6, R7 and R8 meets formula (II) and groups X, Y1-Y4, R1-R14 and n possess the values specified in the patent claim, and also their pharmaceutically acceptable salts. Compounds I show activating effect with respect to PPARδ and/or PPARαreceptors.

EFFECT: applicability of compounds for treatment and prevention of the diseases modulated by PPARδ and PPARα agonists.

22 cl, 8 dwg, 1 tbl, 21 ex

FIELD: chemistry.

SUBSTANCE: new 5-sulphanyl-4H-1,2,4-triazole derivatives of general formula I (meaning of radicals R1-R3 are indicated in the description of the invention), methods of their preparation by liquid-phase parallel synthesis and pharmaceutical composition are claimed.

EFFECT: claimed compounds display high affinity to some subtypes of somostatin receptors of the SST2 and SST5 subtypes and possibility of their usage for treatment of pathological states or diseases involving one or more of the given somostatin receptors

9 cl, 708 ex

FIELD: chemistry.

SUBSTANCE: claimed invention relates to compounds of formula IId and their pharmacologically acceptable salts. In formula IId M represents -CH- or -N-; R2c bonded with carbon atom of 5-member ring and is selected from hydrogen and methyl; R2d is bonded with carbon atom from 6-member ring and selected from hydrogen and fluorine; one of R2a and R2b represents methoxy, and other is Q1X1, where X1 represents -O-, and values of other radicals are given in formula IId, to pharmaceutical composition, inhibiting antiogenesis and/or reducing vessel permeability, which contains as active component compound of formula IId, to application of invention compounds for preparation of medication and to compounds of 7-benzyloxy-4(4-fluorine-2-methylindol-5-iloxy)-6-methoxyquinazoline and 4-(4-fluorine-2- methylindol -5-yloxy)-7-hydroxy-6-methoxyquinazo-line.

EFFECT: development of effective method of obtaining quinazoline compounds.

12 cl, 54 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel compounds of formula I: or its pharmacologically acceptable salts, where n equals 1, 2 or 3; and values of R1, R2, R3, R4, R3', R10, R11 are given in i.1 of formula.

EFFECT: compounds I have ability to inhibit release and/or synthesis of β-amyloid peptide, which allows to apply them in pharmaceutical composition.

25 cl, 3 dwg, 5 ex

FIELD: chemistry.

SUBSTANCE: claimed invention relates to benzenesulphonamide derivatives of formula I and to their salts applied in agriculture. In formula I

X1 represents hydrogen or halogen; X2 chlorine; X3 represents hydrogen; Y represents group -C(A)B; A represents oxygen; B represents oxygen; R1 represents C1-C6-alkyl, which can be optionally substituted with C1-C6-alkoxyl, C1-C6-alkylcarbonyl, C3-C7-cycloalkyl, phenyl-C1-C4-alkyl; Q represents residue Q21; A8, A9 represent oxygen; R29 represents C1-C6-alkyl; R30, R31 represent hydrogen, C1-C6-halogenalkyl.

EFFECT: elaboration of method for obtaining benzenesulphonamide derivatives of formula I, herbicidal preparation based on them, method of obtaining herbicidally active preparations, method used to fight undesirable plant growth, application as herbicides and to benzenesulphonylisocyanates of formula II.

8 cl, 4 tbl, 6 ex

Cynnamide compound // 2361872

FIELD: chemistry.

SUBSTANCE: invention relates to a compound with formula (I) , where Ar1 is an imidazolyl group, which can be substituted with 1-3 substitutes; Ar2 is a pyridinyl group, pyrimidinyl group or phenyl group, which can be substituted with 1-2 substitutes; X1 is (1) -C≡C- or (2) double bond etc., which can be substituted, R1 and R2 are, for example, C1-6-alkyl group or C3-8-cycloalkyl group, which can be substituted; or to a pharmacologically acceptable salt of the said compound and pharmaceutical drugs for lowering production of Aβ42, containing formula (I) compound as an active ingredient.

EFFECT: wider field of use of the compounds.

26 cl, 1119 ex, 31 tbl

FIELD: chemistry.

SUBSTANCE: invention relates to new pyrimidine derivatives with general formula (I), their tautomeric or stereoisomeric form, in free form, in form of pharmaceutically acceptable salt or C1-6alkyl ester which are effective antagonists of CRTH2 (G-protein-associated chemoattractant receptor, ex prone on Th2 cells) and can be used for preventing and treating diseases related to CRTH2 activity, particularly in treatment of allergic diseases such as asthma, allergic rhinitis, atopic dermatitis, diseases related to eosinophil. In formula (I) R1 is hydrogen, or in which n is an integer from 0 to 6; -Q1- is -NH-, -N(C1-6alkyl)- or -O; Y is hydrogen, C1-6alkyl, C3-6cycloalkyl, optionally substituted with C1-6alkyl, C3-6cycloalkyl, condensed with a benzene ring, phenyl, naphthyl or 5-6-member heteroaryl, possibly condensed with a benzene ring, and containing at least one heteroatom, chosen from a group consisting of oxygen and nitrogen, where the said phenyl, naphthyl or heteroaryl are optionally substituted on the displaceable position with one or several substitutes, chosen from a group consisting of cyano, halogen, nitro, guanidine, pyrroyl, sulfamoyl, phenyloxy, phenyl, di(C1-6)alkylamino, C1-6alkanoylamino, C1-6alkyl, optionally mono-, di- or tri-substituted with halogen, C1-6alkoxy, optionally mono-, di- or tri-substituted with halogen and C1-6alkylthio, optionally mono-, di- or tri-substituted with halogen; or phenyl, condensed with 1,3-dioxolane; R2 is hydrogen or C1-6alkyl; R3 is a halogen, C1-6alkoxy, optionally mono-, di- or tri-substituted with halogen, or , R3a and R3b are independently C3-8cycloalkyl or C1-6alkyl, this C1-6alkyl is optionally substituted with hydroxyl, carboxy, C3-6cycloalkylcarbamoyl, C5-6heterocyclocarbonyl containing a heteroatom in form of nitrogen, or C1-6alkoxy, q is an integer from 1 to 3; R3c is hydrogen, hydroxyl or carboxy; Xa is -O-; R4 is hydrogen, halogen, di(C1-6alkyl) amino or C1-6alkyl, optionally substituted C1-6alkoxy or mono- , di- or tri-substituted with halogen; R5 is hydrogen or C1-6alkyl; and R6 is carboxy, carboxamide, nitrile or tetrazolyl.

EFFECT: wider field of use of compounds.

32 cl, 9 tbl, 13 ex

FIELD: chemistry.

SUBSTANCE: invention relates to new substituted 3-sulphur-indoles with formula I: or their pharmaceutically acceptable salts, or their solvates where: R1 represents NR4COR6, NHSO2R5, NHCOR6, 5-6-member heteroaryl, containing 1-2 heteroatoms, independently chosen from N, S and O; R2 represents H, C1-7alkyl; R3 represents quinolyl, phenyl, where the latter is substituted with a halogen, C1-6alkoxy, SO2R4; R4 represents C1-6alkyl; R5 and R6 independently represent C1-6alkyl, phenyl, imidazolyl, all of which can be substituted with NR14R15; R14, R15 each independently represents H, C1-C6alkyl; under the condition that, if R1 represents NHSO2R5, then R3 represents phenyl.

EFFECT: compounds can be used in making medicine for treating asthma, rhinitis or chronic obstructive pulmonary disease (COPD).

10 cl, 37 ex

FIELD: pharmacology.

SUBSTANCE: invention concerns indazol derivatives of general formulae (I) or (II) , where radicals and groups are defined as shown in cl. 1 of invention claim, and their pharmaceutically acceptable salts. Also invention claims medicine, method of medicine obtainment and application of claimed compounds in treatment and/or prevention of fatty acid metabolism derangement and glucose assimilation disorders.

EFFECT: inhibition of hormone-sensitive lipases.

13 cl, 1 tbl, 103 ex

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