Derivatives of substituted 3-sulphonylindazole as 5-hydroxytryptamine-6 ligands

FIELD: chemistry.

SUBSTANCE: invention discloses a compound of formula I

, in which radicals and groups are described in the claims. Said compounds are 5-hydroxytryptamine-6 (5-HT6) ligands and can be used to treat central nervous system disorders associated with or influenced by the 5-HT6 receptor. The invention also relates to a pharmaceutical composition and a method of treating said disorders.

EFFECT: high efficiency of using said derivatives.

19 cl, 13 tbl, 204 ex

 

The text descriptions are given in facsimile form.

1. The compound of the formula I

where X represents O, S, NR, CH2CH2Y, CONR or NRCO;
Y represents O, S or NR;
n represents 0 or an integer selected from 1,2, 3, 4, 5 or 6, if X represents CH2;
n is an integer selected from 1, 2, 3, 4, 5 or 6, if X is a NRCO;
n is an integer selected from 2, 3, 4, 5 or 6, if X represents O, S, NR, CH2Y or CONR;
R represents H or alkyl group;
R1represents H, alkyl or benzyl group which may be substituted with halogen;
R2represents phenyl or naphthyl;
each of R3and R4independently represents H or alkyl group;
each of R5and R6independently represents H, alkyl, alkenyl, monocyclohexyl or group of pyrrolidinyl, and the alkyl may optionally contain NR10R11as a substituent, or R5and R6 together with the atom to which they are attached, can form a cycle containing 5 to 6 atoms, which can optionally contain substituents, selected from alkyl and amino, with this cycle may optionally contain a heteroatom selected from O, N and S;
R7represents a halogen or or8;
m is an integer selected from 0 or 1;
R8represents alkyl; and
each of R10and r11represents H;
or a stereoisomer or pharmaceutically acceptable salt of the compounds.

2. The compound according to claim 1, wherein X represents O, NR, or CH2.

3. The compound according to claim 2, wherein X represents O.

4. The compound according to any one of claims 1 to 3, characterized in that n is 2 or 3.

5. The compound according to any one of claims 1 to 3, wherein R2represents naphthyl.

6. The compound according to any one of claims 1 to 3, wherein R2represents a phenyl group.

7. The compound according to any one of claims 1 to 3, characterized in that each of R5and R6independently represents N or C1-C4alkyl.

8. The compound according to any one of claims 1 to 3, wherein R2represents naphthyl and n is 3.

9. The compound according to claim 1, selected from the group including:
N,N-Dimethyl-2-{[3-(FeNi is sulfonyl)-1H-indazol-5-yl]oxy}ethanamine;
3-(Phenylsulfonyl)-5-(2-piperidine-1-yl-ethoxy)-1H-indazol;
N-Ethyl-2-{[3-(phenylsulfonyl)-1H-indazol-5-yl]oxy}ethanamine;
N-(2-{[3-(Phenylsulfonyl)-1H-indazol-5-yl]oxy}ethyl)propane-2-amine;
N-(2-{[3-(Phenylsulfonyl)-1H-indazol-5-yl]oxy}ethyl)Cyclopentanone;
3-(Phenylsulfonyl)-5-(2-pyrrolidin-1-yl-ethoxy)-1H-indazol;
N-Methyl-2-{[3-(phenylsulfonyl)-1H-indazol-5-yl]oxy}ethanamine;
N,N-Dimethyl-3-{[3-(1-naphthylmethyl)-1H-indazol-5-yl]oxy}propan-1-amine;
N-Methyl-3-{[3-(1-naphthylmethyl)-1H-indazol-5-yl]oxy}propan-1-amine;
N-Ethyl-3-{[3-(1-naphthylmethyl)-1H-indazol-5-yl]oxy}propan-1-amine;
N-Ethyl-N-methyl-3-{[3-(1-naphthylmethyl)-1H-indazol-5-yl]oxy}propan-1-amine;
N,N-Diethyl-3-{[3-(1-naphthylmethyl)-1H-indazol-5-yl]oxy}propan-1-amine;
N-(3-{[3-(1-Naphthylmethyl)-1H-indazol-5-yl]oxy}propyl)butane-1-amine;
N-(3-{[3-(1-Naphthylmethyl)-1H-indazol-5-yl]oxy}propyl)cyclopropane;
N-(3-{[3-(1-Naphthylmethyl)-1H-indazol-5-yl]oxy}propyl)Cyclopentanone;
N-Isopropyl-3-{[3-(1-naphthylmethyl)-1H-indazol-5-yl]oxy}propan-1-amine;
3-(1-Naphthylmethyl)-5-(3-pyrrolidin-1-yl-propoxy)-1H-indazol;
3-(1-Naphthylmethyl)-5-(3-piperidine-1-yl-propoxy)-1H-indazol;
5-(3-Morpholine-4-ylpropionic)-3-(1-naphthylmethyl)-1H-indazol;
(3-{[3-(1-Naphthylmethyl)-1H-indazol-5-yl]oxy}propyl)amine;
N,N-Dimethyl-2-{[3-(1-naphthylmethyl)-1H-indazol-5-yl]oxy}ethanamine;
N-(2-{[3-(1-Naphthylmethyl)-1H-indazol-yl]oxy}ethyl)propane-2-amine;
N-Ethyl-N-methyl-2-{[3-(1-naphthylmethyl)-1H-indazol-5-yl]oxy}ethanamine;
(2-{[3-(1-Naphthylmethyl)-1H-indazol-5-yl]oxy}ethyl)amine;
N-Methyl-2-{[3-(1-naphthylmethyl)-1H-indazol-5-yl]oxy}ethanamine;
N-Ethyl-2-{[3-(1-naphthylmethyl)-1H-indazol-5-yl]oxy}ethanamine;
N,N-Diethyl-2-{[3-(1-naphthylmethyl)-1H-indazol-5-yl]oxy}ethanamine;
N-(2-{[3-(1-Naphthylmethyl)-1H-indazol-5-yl]oxy}ethyl) - butane-1-amine;
N-(2-{[3-(1-Naphthylmethyl)-1H-indazol-5-yl]oxy}ethyl)Cyclopentanone;
N-(2-{[3-(1-Naphthylmethyl)-1H-indazol-5-yl]oxy}ethyl)cyclopropane;
3-(1-Naphthylmethyl)-5-(2-pyrrolidin-1-yl-ethoxy)-1H-indazol;
3-(1-Naphthylmethyl)-5-(2-piperidine-1-yl-ethoxy)-1H-indazol;
5-(2-Morpholine-4-ylethoxy)-3-(1-naphthylmethyl)-1H-indazol;
N-Methyl-2-{[1-methyl-3-(1-naphthylmethyl)-1H-indazol-5-yl]oxy}ethanamine;
N,N-Dimethyl-2-{[1-methyl-3-(1-naphthylmethyl)-1H-indazol-5-yl]oxy}ethanamine;
N-Ethyl-N-methyl-2-{[1-methyl-3-(1-naphthylmethyl)-1H-indazol-5-yl]oxy}ethanamine;
N,N-Diethyl-2-{[1-methyl-3-(1-naphthylmethyl)-1H-indazol-5-yl]oxy}ethanamine;
N-Ethyl-2-{[1-methyl-3-(1-naphthylmethyl)-1H-indazol-5-yl]oxy}ethanamine;
N-(2-{[1-Methyl-3-(1-naphthylmethyl)-1H-indazol-5-yl]oxy}ethyl)propane-2-amine;
1-Methyl-3-(1-naphthylmethyl)-5-(2-pyrrolidin-1-yl-ethoxy)-1H-indazol;
(2-{[1-Benzyl-3-(1-naphthylmethyl)-1H-indazol-5-yl]oxy}ethyl)methylamine;
(2-{[1-Benzyl-3-(1-naphthylmethyl)-1H-indazol-5-yl]oxy}ethyl)dimethylamine;br/> (2-{[1-Benzyl-3-(1-naphthylmethyl)-1H-indazol-5-yl]oxy}ethyl) - ethylamine;
(2-{[1-(3-Chlorobenzyl)-3-(1-naphthylmethyl)-1H-indazol-5-yl]oxy}ethyl)-dimethylamine;
(2-{[1-(3-Chlorobenzyl)-3-(1-naphthylmethyl)-1H-indazol-5-yl] oxy}ethyl) - ethylamine;
3-(1-Naphthylmethyl)-5-(4-piperidine-1-yl-butoxy)-1H-indazol;
N-Methyl-4-{[3-(1-naphthylmethyl)-1H-indazol-5-yl]oxy}butane-1-amine;
N-Ethyl-4-{[3-(1-naphthylmethyl)-1H-indazol-5-yl]oxy}butane-1-amine;
N,N-Dimethyl-4-{[3-(1-naphthylmethyl)-1H-indazol-5-yl]oxy}butane-1-amine;
N-Methyl-4-{[3-(1-naphthylmethyl)-1H-indazol-5-yl]oxy}-N-propylate-1-amine;
N,N-Diethyl-4-{[3-(1-naphthylmethyl)-1H-indazol-5-yl]oxy}butane-1-amine;
3-(1-Naphthylmethyl)-5-(4-pyrrolidin-1-yl-butoxy)-1H-indazol;
(4-{[3-(1-Naphthylmethyl)-1H-indazol-5-yl]oxy}butyl)amine;
(2-{[1-(3-Chlorobenzyl)-3-(1-naphthylmethyl)-1H-indazol-7-yl]oxy}ethyl)amine;
(2-{[1-(3-Chlorobenzyl)-3-(1-naphthylmethyl)-1H-indazol-7-yl]oxy}ethyl)methylamine;
(2-{[1-(3-Chlorobenzyl)-3-(1-naphthylmethyl)-1H-indazol-7-yl]oxy}ethyl) - ethylamine;
1-(3-Chlorobenzyl)-3-(1-naphthylmethyl)-7-(2-piperidine-1-yl-ethoxy)-1H-indazol;
1-(3-Chlorobenzyl)-3-(1-naphthylmethyl)-7-(2-pyrrolidin-1-yl-ethoxy)-1H-indazol;
(2-{[3-(1-Naphthylmethyl)-1H-indazol-7-yl]oxy}ethyl)amine;
N-Methyl-2-{[3-(1-naphthylmethyl)-1H-indazol-7-yl]oxy}ethanamine;
N,N-Dimethyl-2-{[3-(1-naphthylmethyl)-1H-indazol-7-yl]oxy}ethanamine;
N-Ethyl-2-{[3-(1-naphthylmethyl)-1H-indazol-7-yl]the XI}ethanamine;
3-(1-Naphthylmethyl)-7-(2-piperidine-1-yl-ethoxy)-1H-indazol;
3-(1-Naphthylmethyl)-7-(2-pyrrolidin-1-yl-ethoxy)-1H-indazol;
(2-{[1-(3-Chlorobenzyl)-3-(phenylsulfonyl)-1H-indazol-7-yl]oxy}ethyl)methylamine;
(2-{[1-(3-Chlorobenzyl)-3-(phenylsulfonyl)-1H-indazol-7-yl]oxy}ethyl) - ethylamine;
1-(3-Chlorobenzyl)-3-(phenylsulfonyl)-7-(2-pyrrolidin-1 ylethoxy)-1H-indazol;
N-Methyl-2-{[3-(phenylsulfonyl)-1H-indazol-7-yl]oxy}ethanamine;
N-Ethyl-2-{[3-(phenylsulfonyl)-1H-indazol-7-yl]oxy}ethanamine;
N-(2-{[3-(Phenylsulfonyl)-1H-indazol-7-yl]oxy}ethyl) - butane-1-amine;
3-(Phenylsulfonyl)-7-(2-pyrrolidin-1-yl-ethoxy)-1H-indazol;
3-(Phenylsulfonyl)-7-(2-piperidine-1-yl-ethoxy)-1H-indazol;
(2-{[1-Methyl-3-(1-naphthylmethyl)-1H-indazol-7-yl]oxy}ethyl)amine;
N-Ethyl-2-{[1-methyl-3-(1-naphthylmethyl)-1H-indazol-7-yl]oxy}ethanamine;
N,N-Diethyl-2-{[1-methyl-3-(1-naphthylmethyl)-1H-indazol-7-yl]oxy}ethanamine;
1-Methyl-3-(1-naphthylmethyl)-7-(2-piperidine-1-yl-ethoxy)-1H-indazol;
1-Methyl-3-(1-naphthylmethyl)-7-(2-pyrrolidin-1-yl-ethoxy)-1H-indazol;
N-Methyl-2-{[1-methyl-3-(phenylsulfonyl)-1H-indazol-7-yl]oxy}ethanamine;
1-Methyl-3-(phenylsulfonyl)-7-(2-pyrrolidin-1-yl-ethoxy)-1H-indazol;
(2-{[1-(3-Chlorobenzyl)-5-fluoro-3-(1-naphthylmethyl)-1H-indazol-7-yl]oxy}ethyl)dimethylamine;
(2-{[5-fluoro-3-(1-naphthylmethyl)-1H-indazol-7-yl]oxy}ethyl)methylamine;
N-Ethyl-2-{[5-fluoro-3-(1-naphthylmethyl)-1H-indazol-7-yl]oxy}ethanamine;
(2-{[5-fluoro-3-(1-naphthas is sulfonyl)-1H-indazol-7-yl]oxy}ethyl)dimethylamine;
N,N-Diethyl-2-{[5-fluoro-3-(1-naphthylmethyl)-1H-indazol-7-yl]oxy}ethanamine;
5-fluoro-3-(1-naphthylmethyl)-7-(2-piperidine-1-yl-ethoxy)-1H-indazol;
5-fluoro-3-(1-naphthylmethyl)-7-(2-pyrrolidin-1-yl-ethoxy)-1H-indazol;
1-(3-Chlorobenzyl)-5-methoxy-3-(1-naphthylmethyl)-7-(2-piperidine-1-ylethoxy)-1H-indazol;
(2-{[5-Methoxy-3-(1-naphthylmethyl)-1H-indazol-7-yl]oxy}ethyl)methylamine;
(2-{[5-Methoxy-3-(1-naphthylmethyl)-1H-indazol-7-yl]oxy}ethyl)dimethylamine;
5-Methoxy-3-(1-naphthylmethyl)-7-(2-piperidine-1-yl-ethoxy)-1H-indazol;
5-Methoxy-3-(1-naphthylmethyl)-7-(2-pyrrolidin-1-yl-ethoxy)-1H-indazol;
(3-{[1-(3-Chlorobenzyl)-3-(1-naphthylmethyl)-1H-indazol-7-yl]oxy}propyl)-diethylamine;
1-(3-Chlorobenzyl)-3-(1-naphthylmethyl)-7-(3-pyrrolidin-1 ipropose)-1H-indazol;
N-Methyl-3-{[3-(1-naphthylmethyl)-1H-indazol-7-yl]oxy}propan-1-amine;
N,N-Diethyl-3-{[3-(1-naphthylmethyl)-1H-indazol-7-yl]oxy}propan-1-amine;
2-{[3-(Phenylsulfonyl)-1H-indazol-7-yl]oxy}ethanamine;
2-{[5-fluoro-3-(phenylsulfonyl)-1H-indazol-7-yl]oxy}ethanamine;
2-{[3-(1-Naphthylmethyl)-1H-indazol-4-yl]oxy}ethanamine;
N,N-Dimethyl-2-{[3-(1-naphthylmethyl)-1H-indazol-4-yl]oxy}ethanamine;
3-(1-Naphthylmethyl)-4-(2-piperidine-1-yl-ethoxy)-1H-indazol;
3-(1-Naphthylmethyl)-4-(2-pyrrolidin-1-yl-ethoxy)-1H-indazol;
2-{[3-(1-Naphthylmethyl)-1H-indazol-6-yl]oxy}ethanamine;
N-Methyl-2-{[3-(1-naphthylmethyl)-1H-indazol-6-yl]oxy}ethanamine;
N-[2-(Dimethylamino)ethyl]-3-(1-naphthylmethyl)-1H-indazol-5-carboxamide;
(3S)-N-{[3-(1-Naphthylmethyl)-1H-indazol-5-yl]methyl}pyrrolidin-3-amine;
N-{[3-(1-Naphthylmethyl)-1H-indazol-5-yl]methyl}ethane-1,2-diamine;
N-[3-(1-Naphthylmethyl)-1H-indazol-5-yl]ethane-1,2-diamine;
N1-[3-(l-Naphthylmethyl)-1H-indazol-5-yl]-beta-alaninate;
(2S)-3-Methyl-N1-[3-(1-naphthylmethyl)-1H-indazol-5-yl]butane-1,2-diamine;
N-[3-(1-Naphthylmethyl)-1H-indazol-7-yl]ethane-1,2-diamine;
N3N3-Dimethyl-N-[3-(1-naphthylmethyl)-1H-indazol-7-yl]-beta-alaninate;
N-[3-(1-Naphthylmethyl)-1H-indazol-7-yl]-3-piperidine-1-ylpropionic;
N-[3-(1-Naphthylmethyl)-1H-indazol-7-yl]-beta-alaninate;
N-[3-(1-Naphthylmethyl)-1H-indazol-6-yl]-beta-alaninate;
N3N3-diethyl-N-[3-(1-naphthylmethyl)-1H-indazol-7-yl]-beta-alaninate;
N-[3-(1-Naphthylmethyl)-1H-indazol-6-yl]-3-piperidine-1-ylpropionic;
N-[3-(1-Naphthylmethyl)-1H-indazol-6-yl]ethane-1,2-diamine;
N,N-Dimethyl-N-{2-[3-(phenylsulfonyl)-1H-indazol-7-yl]ethyl}amine;
N-{2-[3-(Phenylsulfonyl)-1H-indazol-7-yl]ethyl}cyclopropanation;
{2-[3-(Phenylsulfonyl)-1H-indazol-7-yl]ethyl}amine;
N-Methyl-N-{2-[3-(phenylsulfonyl)-1H-indazol-5-yl]ethyl}amine;
N,N-Dimethyl-N-{2-[3-(phenylsulfonyl)-1H-indazol-5-yl]ethyl}amine;
N,N-Dimethyl-N-{3-[3-(phenylsulfonyl)-1H-indazol-5-yl]propyl}amine;
N-{3-[3-(Phenylsulfonyl)-1H-indazol-5-yl]propyl}cyclopropanation;
{3-[3-(Phenylsulfonyl)-1H-indazol-5-yl]propyl}amine;
{4-[3-(Phenylsulfonyl)-1H-indazol-5-the l]butyl}amine;
N,N-Dimethyl-3-[3-(1-naphthylmethyl)-1H-indazol-5-yl]propan-1-amine;
N-Methyl-3-[3-(1-naphthylmethyl)-1H-indazol-5-yl]propan-1-amine;
N-Ethyl-3-[3-(1-naphthylmethyl)-1H-indazol-5-yl]propan-1-amine;
N-Isopropyl-3-[3-(1-Naphthylmethyl)-1H-indazol-5-yl]propan-1-amine;
N-Ethyl-N-methyl-3-[3-(1-naphthylmethyl)-1H-indazol-5-yl]propan-1-amine;
3-(1-Naphthylmethyl)-5-(3-pyrrolidin-1-yl-propyl)-1H-indazol;
{3-[3-(1-Naphthylmethyl)-1H-indazol-5-yl]propyl}amine;
{4-[3-(1-Naphthylmethyl)-1H-indazol-5-yl]butyl}amine;
N,N-Dimethyl-4-[3-(1-naphthylmethyl)-1H-indazol-5-yl]butane-1-amine;
N-Ethyl-4-[3-(1-naphthylmethyl)-1H-indazol-5-yl]butane-1-amine;
N-Isopropyl-4-[3-(1-naphthylmethyl)-1H-indazol-5-yl]butane-1-amine;
N-Ethyl-N-methyl-4-[3-(1-naphthylmethyl)-1H-indazol-5-yl]butane-1-amine;
3-(1-Naphthylmethyl)-5-(4-pyrrolidin-1-yl-butyl)-1H-indazol;
3-(1-Naphthylmethyl)-5-(piperazine-1-yl-methyl)-1H-indazol;
5-[(4-Methylpiperazin-1-yl)methyl]-3-(1-naphthylmethyl)-1H-indazol;
5-[(3-Methylpiperazin-1-yl)methyl]-3-(1-naphthylmethyl)-1H-indazol;
5-[(3,5-Dimethylpiperazine-1-yl)methyl]-3-(1-naphthylmethyl)-1H-indazol;
5-{[(3S)-3-Methylpiperazin-1-yl]methyl}-3-(1-naphthylmethyl)-1H-indazol;
5-{[(3R)-3-Methylpiperazin-1-yl]methyl}-3-(1-naphthylmethyl)-1H-indazol;
(3R)-1-{[3-(1-Naphthylmethyl)-1H-indazol-5-yl]methyl}pyrrolidin-3-amine;
the stereoisomers of these compounds; and pharmaceutically acceptable salts of these with the joining.

10. The compound, which is represented by N,N-Dimethyl-3-{[3-(1-naphthylmethyl)-1H-indazol-5-yl]oxy}propan-1-amine or a pharmaceutically acceptable salt of the compounds.

11. The connection of claim 10, which represents a N,N-Dimethyl-3-{[3-(1-naphthylmethyl)-1H-indazol-5-yl]oxy}propan-1-amine hydrochloride.

12. The connection of claim 10, which represents a N,N-Dimethyl-3-{[3-(1-naphthylmethyl)-1H-indazol-5-yl]oxy}propan-1-amine.

13. The compound according to claim 1, selected from the following compounds:
N-ethyl-N-methyl-2-(3-(phenylsulfonyl)-1H-indazol-5-yloxy)ethanamine;
[2-(3-benzazolyl-1H-indazol-5-yloxy)-ethyl]diethylamine;
N-(2-(3-(phenylsulfonyl)-1H-indazol-5-yloxy)ethyl) - butane-1-amine;
N-(2-(3-(phenylsulfonyl)-1H-indazol-5-yloxy)ethyl)cyclopropane;
4-(2-(3-(phenylsulfonyl)-1H-indazol-5-yloxy)ethyl)morpholine;
2-(3-(phenylsulfonyl)-1H-indazol-5-yloxy)ethanamine;
{2-[1-Benzyl-3-(naphthalen-1-sulfonyl)-1H-indazol-5-yloxy]-ethyl}-ethyl-methylamine;
N-(2-(1-benzyl-3-(naphthalen-1-yl-sulfonyl)-1H-indazol-5-yloxy)ethyl)propane-2-amine;
2-(1-benzyl-3-(naphthalen-1-yl-sulfonyl)-1H-indazol-5-yloxy)-N,N-diethylethanamine;
1-benzyl-3-(naphthalen-1-yl-sulfonyl)-5-(2-(pyrrolidin-1-yl)ethoxy)-1H-indazol;
2-(1-(3-Chlorobenzyl)-3-(naphthalen-1-yl-sulfonyl)-1H-indazol-5-yloxy)-N-ethyl-N-methylethanamine;
2-(1-(3-Chlorobenzyl)-3-(naphthalen-1-yl-sulfonyl)-1H-indazol-5-yloxy)-N,N-diethylethanamine;
N-(2(1-(3-Chlorobenzyl)-3-(naphthalen-1-yl-sulfonyl)-1H-indazol-5-yloxy)ethyl)propane-2-amine;
1-(3-Chlorobenzyl)-3-(naphthalen-1-yl-sulfonyl)-5-(2-(pyrrolidin-1-yl)ethoxy)-1H-indazol;
2-(1-(3-Chlorobenzyl)-3-(naphthalen-1-yl-sulfonyl)-1H-indazol-5-yloxy)-N-methylethanamine;
2-(1-(3-Chlorobenzyl)-3-(naphthalen-1-yl-sulfonyl)-1H-indazol-7-yloxy)-N,N-diethylethanamine;
N-(2-(1-(3-Chlorobenzyl)-3-(naphthalen-1-yl-sulfonyl)-1H-indazol-7-yloxy)ethyl) - butane-1-amine;
2-(1-(3-Chlorobenzyl)-3-(phenylsulfonyl)-1H-indazol-7-yloxy)-N,N-diethylethanamine;
N-(2-(1-(3-Chlorobenzyl)-3-(phenylsulfonyl)-1H-indazol-7-yloxy)ethyl) - butane-1-amine;
1-(3-Chlorobenzyl)-3-(phenylsulfonyl)-7-(2-(piperidine-1-yl)ethoxy)-1H-indazol;
2-(1-(3-Chlorobenzyl)-3-(phenylsulfonyl)-1H-indazol-7-yloxy)-N,N-diethylethanamine;
N,N-dimethyl-2-(1-methyl-3-(naphthalen-1-yl-sulfonyl)-1H-indazol-7-yloxy)ethanamine;
N-(2-(1-methyl-3-(naphthalen-1-yl-sulfonyl)-1H-indazol-7-yloxy)ethyl) - butane-1-amine;
N-ethyl-2-(1-methyl-3-(phenylsulfonyl)-1H-indazol-7-yloxy)ethanamine;
N,N-diethyl-2-(1-methyl-3-(phenylsulfonyl)-1H-indazol-7-yloxy)ethanamine;
1-methyl-3-(phenylsulfonyl)-7-(2-(piperidine-1-yl)ethoxy)-1H-indazol;
2-(1-(3-Chlorobenzyl)-5-fluoro-3-(naphthalen-1-yl-sulfonyl)-1H-indazol-7-yl-oxy)ethanamine;
2-(1-(3-Chlorobenzyl)-5-fluoro-3-(naphthalen-1-yl-sulfonyl)-1H-indazol-7-yloxy)-N-methylethanamine;
2-(1-(3-Chlorobenzyl)-5-fluoro-3-(naphthalen-1-yl-sulfonyl)-1H-indazol-7-yloxy)-N-tiletamine;
2-(1-(3-Chlorobenzyl)-5-fluoro-3-(naphthalen-1-yl-sulfonyl)-1H-indazol-7-yloxy)-N,N-diethylethanamine;
1-(3-Chlorobenzyl)-5-fluoro--(naphthalen-1-yl-sulfonyl)-7-(2-(piperidine-1-yl)ethoxy)-1H-indazol;
1-(3-Chlorobenzyl)-5-fluoro-3-(naphthalen-1-yl-sulfonyl)-7-(2-(pyrrolidin-1-yl)ethoxy)-1H-indazol;
2-(1-(3-Chlorobenzyl)-5-methoxy-3-(naphthalen-1-yl-sulfonyl)-1H-indazol-7-yl-oxy)-N-methylethanamine;
2-(1-(3-Chlorobenzyl)-5-methoxy-3-(naphthalen-1-yl-sulfonyl)-1H-indazol-7-yl-oxy)-N-tiletamine;
2-(1-(3-Chlorobenzyl)-5-methoxy-3-(naphthalen-1-yl-sulfonyl)-1H-indazol-7-yloxy)-N,N-dimethylethanamine;
1-(3-Chlorobenzyl)-5-methoxy-3-(naphthalen-1-yl-sulfonyl)-7-(2-(pyrrolidin-1-yl)ethoxy)-1H-indazol;
3-(1-(3-Chlorobenzyl)-3-(naphthalen-1-yl-sulfonyl)-1H-indazol-7-yloxy)-N-methylpropan-1-amine;
3-(1-(3-Chlorobenzyl)-3-(naphthalen-1-yl-sulfonyl)-1H-indazol-7-yloxy)-N-ethylpropane-1-amine;
3-(1-(3-Chlorobenzyl)-3-(naphthalen-1-yl-sulfonyl)-1H-indazol-7-yloxy)-N,N-DIMETHYLPROPANE-1-amine;
1-(3-Chlorobenzyl)-3-(naphthalen-1-yl-sulfonyl)-7-(3-(piperidine-1-yl)propoxy)-1H-indazol;
N-ethyl-3-(3-(naphthalen-1-yl-sulfonyl)-1H-indazol-7-yloxy)propan-1-amine;
N,N-dimethyl-3-(3-(naphthalen-1-yl-sulfonyl)-1H-indazol-7-yloxy)propan-1-amine;
3-(naphthalen-1-yl-sulfonyl)-7-(3-(piperidine-1-yl)propoxy)-1H-indazol;
N-methyl-2-(3-(naphthalen-1-yl-sulfonyl)-1H-indazol-4-yloxy)ethanamine;
N,N-dimethyl-2-(3-(naphthalen-1-yl-sulfonyl)-1H-indazol-6-yloxy)ethanamine;
3-(naphthalen-1-yl-sulfonyl)-6-(2-(piperidine-1-yl)ethoxy)-1H-indazol;
3-(naphthalen-1-yl-sulfonyl)-6-(2-(pyrrolidin-1-yl)ethoxy)-1H-indazol;
3-(naphthalen-1-yl-sulfonyl)-N-(2-(piperidine-1-yl)ethyl)-1H-in the azole-5-carboxamide;
N,N,N'-Trimethyl-N'-{[3-(1-naphthylmethyl)-1H-indazol-5-yl]methyl}ethane-1,2-diamine;
N1N1-dimethyl-N2-((3-(naphthalen-1-yl-sulfonyl)-1H-indazol-5-yl)methyl)ethane-1,2-diamine;
N1(3-(naphthalen-1-ylsulphonyl)-1H-indazol-5-yl)propane-1,2-diamine;
3-(dimethylamino)-N-(3-(naphthalen-1-yl-sulfonyl)-1H-indazol-6-yl)propanamide;
3-(diethylamino)-N-(3-(naphthalen-1-yl-sulfonyl)-1H-indazol-6-yl)propanamide;
N-methyl-2-(3-(phenylsulfonyl)-1H-indazol-7-yl)ethanamine; and N-isopropyl-3-(3-(phenylsulfonyl)-1H-indazol-5-yl)propan-1-amine;
or pharmaceutically acceptable salts of such compounds.

14. A method of treating disorders of the Central nervous system, which is associated with 5-HT6receptor, or which 5-HT6the receptor is affected, the patient who needs such treatment, including the introduction of the indicated patient a therapeutically effective amount of a compound according to any one of claims 1 to 13.

15. The method according to 14, characterized in that the breach is a cognitive disorder, developmental disorders or neurodegenerative disorder.

16. The method according to 14, characterized in that the breach is a cognitive disorder.

17. The method according to 14, characterized in that the breach selected from the group including an impaired ability to learn, attention deficit disorder, down syndrome the fragile X chromosome and autism.

18. The method according to 14, wherein the disease is a neurodegenerative consequences of a stroke or head injury.

19. Pharmaceutical composition for the binding of 5-HT6receptor containing a pharmaceutically acceptable carrier and an effective amount of a compound according to any one of claims 1 to 13.



 

Same patents:

FIELD: chemistry.

SUBSTANCE: invention relates to novel compounds of formula I or pharmaceutically acceptable salts thereof, which have receptor tyrosine kinase type I inhibiting properties and can be used in treating hyperproliferative disorders in mammals. In general formula

,

A is O or S; G is N; B is a 6-member aryl or 5-6-member heteroaryl ring containing a sulphur atom as a heteroatom; E is

, , , , , X is N or CH; D1, D2 and D3 independently denote N or CR19; D4 and D5 independently denote N or CR19 and D6 is O, S or NR20, where at least one of D4 and D5 is CR19; D7, D8, D9 and D10 independently denote N or CR19, where at least one of D7, D8, D9 and D10 is N; R1 is H or C1-C6 alkyl; each R2 independently denotes halogen, cyano, nitro etc, trifluoromethyl, difluoromethyl, fluoromethyl, fluoromethoxy, difluoromethoxy, trifluoromethoxy, azido, -SR18, -OR15, -C(O)R15, -C(O)OR15, -NR14C(O)OR18, -OC(O)R15, -NR14SO2R18, -SO2NR15R14, -NR14C(O)R15, -C(O)NR15R14, -NR15C(O)NR15R14, -NR13C(NCN)NR15R14, -NR15R14, C1-C12alkyl, C2-C12 alkenyl, alkynyl, saturated or partially unsaturated C3-C10cycloalkyl, C3-C10cycloalkyl-C1-C12alkyl, -S(O)p(C1-C6alkyl), -S(O)p(CR13R14)q-phenyl, phenyl, phenyl-C1-3-alkyl, 5-6-member heteroaryl, 5-6-member heteroaryl-C1-C3-alkyl, saturated or partially unsaturated 3-8-member heterocyclyl, 5-6-member heterocyclyl-C1-C3-alkyl, -O(CR13R14)q-phenyl, NR15(CR13R14)q-phenyl, O(CR13R14)q-(5-6-member heteroaryl), NR13(CR13R14)q-(5-6-member heteroaryl, -O(CR13R14)q-(3-8-member heterocyclyl) or -NR15(CR13R14)q-3-8-member heterocyclyl), each R3 denotes Z, where Z is selected from and , W is O or S; W2 is O or S;V is CR8R9, R8b is H or C1-C6alkyl; each of R6, R8, R8a and R9 independently denotes hydrogen, trifluoromethyl, C1-C12alkyl etc.

EFFECT: improved properties and high efficiency of using the compounds.

25 cl, 13 dwg, 1 tbl, 36 ex

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of formula (I) and pharmaceutically acceptable salts thereof. In formula (I) Y is C-R4 and Z is CH; or Y is C-R4 and Z is N; or Y is N and Z is CH; R1 is a 5- or 6-member ring of formula (II) or (III): R2 is H, C1-C7-alkyl; R3 is phenyl, pyrazolyl, isoxazolyl, pyridinyl, pyrimidinyl or pyrazinyl, which can possibly be substituted with one, two or three substitutes selected from a group consisting of: CN, CI, F, Br, CF3, CHF2, C1-C7-alkyl, -O-C1-C7-alkyl, -(CH2)m-Rc, -O-CH2F, -O-CHF2, -O-CF3, -S(O)2-Rd; R4 is H, C1-C7-alkyl; R5 is H, CI, F, Br, CN, CF3, CHF2, C1-C7-alkyl, -C3-C6-cycloalkyl, -(CH2)m-Re or -(CO)-NRiRj; R6 is C1-C7-alkyl; R7 is H, CI, F, CN or C1-C7-alkyl; Rc is -OH; Rd is C1-C7-alkyl; Re is -CH2F, -CHF2, -CF3, CN, C1-C7-alkoxy; Ri, Rj independently denote H or C1-C7-alkyl; m equals 1-4. The invention also relates to a medicinal agent having mGluR5a receptor antagonist properties, containing one or more of the disclosed compounds as an active component.

EFFECT: high efficiency of the medicinal agent.

24 cl, 208 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a compound of formula I or tautomer thereof or pharmaceutically acceptable salts thereof, where R2 is C1-3-alkyl or cyclopropyl; R9 is a halogen, C1-3-alkyl, -O-(C1-3-alkyl), -S-(C1-3alkyl) or CF3 and p equals 1-2. The disclosed compounds are Aurora protein kinase inhibitors. Said compounds can be used in a method of inhibiting Aurora protein kinase activity. The invention also discloses pharmaceutically acceptable compositions containing such compounds; and a method of treating proliferative disorders in a patient using said compounds.

EFFECT: more effective use of the compounds.

11 cl, 7 tbl, 20 ex

Iap inhibitors // 2425838

FIELD: chemistry.

SUBSTANCE: invention relates to novel compounds of formula

, which can inhibit binding of protein Smac with apoptosis protein inhibitor (IAP).

EFFECT: improved properties of the inhibitor.

4 cl, 198 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a compound of formula (II), consisting of a core and groups -R-L-X' attached to said core, nA(-R-L-X')n (II). A denotes an aromatic ring selected from [1,3,5]triazinane-2,4,6-trione ring or a benzene ring, possibly substituted with one or more C1-C3-alkyls; R denotes a benzene ring residue possibly substituted with C1-C3-alkyl, and R can be bonded to A through a group of formula , where Rb denotes C1-C3-alkyl; L denotes a linker group - CZ1Z2-CO-N(Rb)-*; where * denotes bonding of R to the said linker group, Z1 and Z2 denote hydrogen, or Z1 denotes hydrogen and Z2 denotes methyl, and Rb denotes H or C1-C3-alkyl; X' denotes a paramagnetic chelate consisting of chelator X and a paramagnetic metal ion M; where X denotes a residue of 1,4,7,10-tetraazacyclododecane-1,4,7-triacetic acid (DO3A), M denoets Gd3+; n equals 3. If A denotes a benzene ring, R can denote a cyclic group condensed with the core A, which corresponds to the following formula:

, where Qa denotes C(Rc)2, and Rc denotes CH2OCH3; L and X' assume values given above. The invention also discloses a composition, use of the composition, a compound of formula (I), a method of producing the compound of formula (I) (versions) and a method of producing the compound of formula (II).

EFFECT: obtaining compounds which function well as magnetic resonance (MR) contrast agents in strong magnetic fields.

8 cl, 9 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel pyrazole derivatives of general formula I

and pharmaceutically acceptable salts thereof, where n equals 1 or 2, m equals 0, 1 or 2, A contains in the ring a group selected from -CR1=, -CR2=, -CR3=, -CR4= and -CR5=, where 0 or 1 in these groups is replaced with N, R1, R2, R3, R4 and R5 are independently selected from a group comprising hydrogen, hydroxy, halogen, cyano, cyano(C1-C6)alkyl, C4-C6 heterocycloalkyl-C0-alkyl, where the said heterocycloalkyl contains 1-2 heteroatoms selected from nitrogen and oxygen atoms, C5heteroaryl-(C0-C4)alkyl, where the said heteroaryl contains 1-4 heteroatoms selected from nitrogen atoms, -XSO2R11, -XSO2NR11R12, -XSO2NR11C(O)R12, -XC(NR11)NR11OR12, -XCR11=NOR12, -XC(O)R11, -XC(O)OR11, -XNR11R12, -XC(O)NR11R12, -XOC(O)NR11R12, -XNR11C(O)NR11R12, -XNR11XOR12; -XN(XOR12)2, -XNR11XC(O)OR12 -XNR11XNR11C(O)R12 -XNR11XNR11R12, -XNR11C(O)R12, where each X is independently selected from a group comprising a chemical bond and C1-C4alkylene, each R11 is selected from a group comprising hydrogen and C1-C6alkyl, and R12 is selected from a group comprising hydrogen, C1-C6alkyl and phenyl, or R11 and R12 together with a nitrogen atom to which R11 and R12 are bonded form C6heterocycloalkyl. Said heteroaryl or heterocycloalkyl in R1, R2, R3, R4 or R5 optionally contains one substitute selected from a group comprising hydroxyl, cyano, C1-C6alkyl, hydroxyl(C1-C6)alkyl and carboxy, R6 and R7 independently denote hydrogen, R8 is selected from a group comprising C1-C6alkyl, halogen(C1-C3)alkyl, -CH2OR8a and -COOR8a or two R8 groups bonded to different carbon atoms, together form a (C1-C2)alkyl bridge, or two R8a groups bonded to one carbon atom form a (C3-C8)cycloalkyl group, where R8a is selected from a group comprising hydrogen and C1-C6alkyl, R9 is selected from a group comprising phenyl and C6heteroaryl, where the said heteroaryl contains 1-2 heteroatoms selected from nitrogen atoms, and C9heteroaryl, where the said heteroaryl contains 1-2 heteroatoms selected from nitrogen and oxygen atoms, where the said phenyl or heteroaryl in R9 is optionally substituted with 1-2 substitutes independently selected from a group comprising halogen, cyano, hydroxy, C1-C3alkyl, halogen(C1-C3)alkyl, hydroxy(C1-C3)alkyl, -C(O)R13, -C(O)NR13R14, where each of R13 and R14 is independently selected from a group comprising hydrogen and C1-C6alkyl, R10 denotes hydrogen, Y and Z are independently selected from a group comprising CR20 and N, where R20 denotes hydrogen, provided that compounds of formula I do not include compounds of formula II, which are described in claim 1, and provided that compounds of formula I do not include compounds which are: 1-(4-fluorophenyl)-4-((3-phenyl-1H-pyrazol-4-yl)methyl)piperazine, 1- ((3-(4-fluorophenyl)-1H-pyrazol-4-yl)methyl)-4-(4-(trifluoromethyl)-(pyridin-2- yl)piperazine, 1-((3-(4-fluorophenyl)-1H-pyrazol-4-yl)methyl)-4-(5-(trifluoromethyl)-(pyridin-2-yl)piperazine and 1-((3-(4-fluorophenyl)-1H-pyrazol-4-yl)methyl)-4-(5-fluoropyridin-2-yl)piperazine. The invention also relates to specific compounds obtained.

EFFECT: novel pyrazole derivatives which can be used in treating diseases or disorders which are mediated by disrupted activation of the said compound are obtained.

8 cl, 1 tbl, 4 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to drugs and concerns a combination for tumour cell growth inhibition containing a cytotoxic compound selected from camptothecin compounds; metabolic antagonists; periwinkle alkaloids; taxanes; platinum compounds; topoisomerase 2 inhibitors; and a combination of two or more said types, or a signal transfer inhibitor selected from antibodies a target of which is EGFR receptor; tyrosine kinase EGFR inhibitors; from antibodies a target of which is a VEGF/VEGF receptor system; PDGFR inhibitors; Raf inhibitors and PKB transfer inhibitors in an effective amount and a compound of formula (IV).

, where R1, R2, R11, T, U and g have the values specified in formula.

EFFECT: what is offered is a pharmaceutical composition, a method for tumour cell growth inhibition, a method of treating a malignant growth in a patient and application of the combination for preparing a drug; the new effective combinations for tumour cell growth inhibition are presented.

77 cl, 20 dwg, 7 tbl, 257 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to a new maleate salt of 4-((4-fluorine-2-methyl-1H-indole-5-yl)oxy)-6-methoxy-7-(3-(pyrrolidine-1-yl)propoxy)quinazoline in a crystalline form A or B which exhibit the improved use properties, particularly shows higher stability. The invention also concerns versions of methods of producing the maleate salt of 4-((4-fluorine-2-methyl-1H-indole-5-yl)oxy)-6-methoxy-7-(3-(pyrrolidine-1-yl)propoxy)quinazoline in the crystalline form A or B, to a pharmaceutical composition containing them and to an application for preparing a drug used for producing an anticancer effect.

EFFECT: preparation of the compounds to be used for producing an antiangiogenic action and/or reducing a vascular permeability.

14 cl, 3 ex, 5 tbl, 10 dwg

FIELD: chemistry.

SUBSTANCE: described are novel compounds of general formula

:, where X denotes halogen or (C1-C3)alkyl possibly substituted with a halogen; Y denotes hydrogen; R denotes hydrogen, halogen, cyano, (C1-C6)alkyl or (C2-C6)alkenyl possibly substituted with a halogen, (C2-C6)alkynyl possibly substituted with a halogen or hydroxy, (C1 -C6)alkoxy or (C2-C6)alkenyloxy, possibly substituted with a halogen, (C1-C6)alkoxycarbonyl, (C1-C6)alkoxyamino(C1-C3)alkyl, phenyl, phenoxy, pyridyloxy or pyrimidyloxy, possibly substituted; n is an integer from 1 to 5; a plant disease control agent and a plant disease control method.

EFFECT: obtaining compounds with a wider suppressing spectrum at low doses of chemical processing, thus facilitating use as a plant disease control agent for agricultural and horticultural use, as well as reduced harmful effect on the environment.

4 cl, 6 tbl, 10 ex

FIELD: chemistry.

SUBSTANCE: present invention relates to a method of producing (E)-4-(6,7-dimethoxy-2-methyl-3-quinolyl)-3-buten-2-one derivatives of formula I, where Ia: R1 and R2 - CH3; Ib: R1 - CH3, R2 - C6H5; Ic: R1 - CH3, R2 - o-NO2C6H4; Id: R1 - t-Bu, R2 - C6H5; Ie: R1 - t-Bu, R2 - p-OCH3C6H4; If: R1 - p-BrC6H4, R2 - Ph; Ig: R1 -CH3, R2 - thiophene; Ih: R1 - t-Bu, R2 - CH2CH2Ph; Ii: R1 - t-Bu, R2 - CH2CH2Cl; Ij: R1 - p-BrC6H4, characterised by that ortho-aminoacylbenzylfuran derivatives of formula II are boiled in benzene in the presence of phosphorus oxychloride with a reflux condenser for 1.5-3.5 hours depending on substitutes R1 and R2.

EFFECT: obtaining (E)-4-(6,7-dimethoxy-2-methyl-3-quinolyl)-3-buten-2-one derivatives, pitavastatin analogues, and introduction of the required substitute into the desired compound with simultaneous formation of a quinoline nucleus.

2 tbl, 6 ex

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of formula

and pharmaceutically acceptable salts thereof, where substitutes R1-R4 are as defined in claim 1. Said compounds have 11β-hydroxysteroid dehydrogenase 1 (11β-HSD1) enzyme inhibiting activity.

EFFECT: compounds can be used in form of a pharmaceutical composition.

15 cl, 1 tbl, 94 ex

FIELD: medicine.

SUBSTANCE: invention refers to new compounds with pharmacological activity to sigma-receptor, and more specifically to pyrazole derivatives of formula (I) in which radicals and symbols have the values defined in cl. 1 of the patent claim; to a method for preparing such compounds; to a pharmaceutical composition containing them and to their application for manufacturing a medicinal agent for treatment and prevention of a sigma-receptor mediated disease or a condition, particularly for treatment of psychotic illness, such as depression, anxiety or schizophrenia, and neuropathic or inflammatory pain, including allodynia and/or hyperalgesia.

EFFECT: improved clinical effectiveness.

11 cl, 2 dwg, 1 tbl, 112 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to novel compounds, which possess qualities to estrogen modulators, of general formula (1) or its pharmaceutically acceptable salt, where R1 represents hydrogen atom or (C1-C6)alkyl, -SO2NR7R8, phenyl (C1-C3)alkyl or (C1-C3)alkyl, substituted with 5-8-member heterocyclic radical, containing nitrogen atom; R2 and R3 each independently represents hydrogen atom or hydroxyl, halogen atom or (C1-C6)alkoxy; X represents O, S, SO, SO2 or NR4; R4 represents hydrogen atom or (C1-C6)alkyl, phenyl, phenyl(C1-C3)alkyl, (C1-C3)alkyl, substituted with 5-8-member saturated heterocyclic radical, containing one nitrogen atom, or group -COR7, -CO2R7 or -SO2NR7R8, where phenyl is not substituted or is substituted with at least one substituent, selected from group which includes hydroxyl, halogen atom or phenyl(C1-C3)alkoxy; Y represents direct bond, -(CR10R11)n- or -R10C=CR11-; R7 and R8 each independently represents hydrogen atom or (C1-C6)alkyl group; R10 and R11 each independently represent hydrogen atom or cyano, or group CONR7R8; n equals 1 or 2; A represents (C3-C12)cycloalkyl or phenyl, where phenyl is not substituted or is substituted with at least one substituent, selected from group which includes hydroxyl, halogen atom, (C1-C3)alkyl, (C1-C3)alkoxy; when X represents NR4, Y and R2 together with containing them indazole cycle can also form 1H-pyrano[4,3,2-cd)indazole; on condition that: 1) when X represents O, S or NR4, R1 represents hydrogen atom or (C1-C6)alkyl, and Y stands for direct bond, then A is not optionally substituted phenyl; 2) when X represents O, R1O represents 6-OH or 6-OCH3, Y represents direct bond and A represents cyclopeptyl, then (R2, R3) or (R3, R2) are different from (H, CI) in position 4, 5; 3) when X stands for O, R1O represents 6-OH, R2 and R3 represent H, and Y represents CH=CH, then A is not phenyl or methoxyphenyl; 4) when X represents SO2, A represents phenyl and R1O represents 5-or 6-OCH3, then (R2, R3) or (R3, R2) are different from (H, OCH3) in position 6- or 5-, compound not being one of the following: 3-phenyl-5-(phenylmethoxy)-1H-indazole; n-hydroxy-3-phenylmethyl-7-(n-propyl)-benz[4,5]isoxazole; 3-(4-chlorphenylmethyl)-6-hydroxy-7-(n-propyl)-benz[4,5]isoxazole; 6-hydroxy-3-(2-phenylethyl)-7(n-propyl)-benz[4,5]isoxazole; 3-cyclopropyl-6-hydroxy-3-phenylmethyl-7-(n-propyl)-benz[4,5|isoxazole; 3-cyclohexylmethyl-6-hydroxy-3-phenylmethyl-7-propyl-benz[4,5]isoxazole. Invention also relates to pharmaceutical composition, application and method of prevention and treatment of disease, where modulation of estrogen receptors is required.

EFFECT: obtaining novel compounds, which possess qualities of estrogen receptors modulators.

18 cl, 7 dwg, 8 tbl, 97 ex

FIELD: chemistry.

SUBSTANCE: invention refers to compounds of the formula (I) and pharmaceutically acceptable salts, where R1-R7 mean the same as provided in the invention description and claim. Compounds of the formula (I) are specific inhibitors of 11b-HSD1. They can be applied in treatment and/or prevention of diseases caused by dysfunctions related to 11b-HSD1 enzyme, particularly in treatment and/or prevention of metabolic diseases, obesity, dyslipidemia, hypertension and/or diabetes, especially diabetes type "П". Additionally subject matter includes pharmaceutical composition for treatment and/or prevention of the said diseases.

EFFECT: improved efficiency of derivatives.

21 cl, 1 tbl, 146 ex

FIELD: medicine.

SUBSTANCE: there are described new compounds of general formula

where Xa represents 2 to 4 condensed cycloalkyl, aryl, heterocyclic rings containing 1 to 2 heteroatoms, chosen of N and O, and heteroaryl rings containing 1 to 4 heteroatoms, chosen of N, O or S where said rings can be additionally substituted. (Radical values R1-R4, R1, Y and n are specified in the patent claim), specific representatives of said compounds and a pharmaceutical composition containing them.

EFFECT: new compounds are effective in stimulation of endogenous development or release of growth hormone and can be used in treating obesity, osteoporosis and for increasing muscle bulk and muscle strength.

17 cl, 339 ex, 10 tbl

FIELD: chemistry.

SUBSTANCE: invention refers to new 3-amino-1-arylpropylindoles of formula I: or to its pharmaceutically acceptable salts, where: p is equal to 1 or 2; Ar means: indolyl, 2,3-dihydroindolyl, indazolyl, benzimidazolyl, benzofuranyl, and each can be substituted; R1 means: phenyl, naphthyl, thienyl, pyridinyl, pyrimidinyl, pyridazinyl, pyrazinyl, thiazolyl, isoxazolyl, pyrazolyl, quinolinyl, aryl-C1-6alkyl where each can be substituted; C3-6cycloalkyl; branched C1-6alkyl; R2 and R3 each independently stands for: H, C1-6alkyl; OH-C1-6alkyl; benzyl; or R2 and R3 together with nitrogen atom whereto attached can form optionally substituted tetra-heptamerous ring, optionally with additional heteroatom chosen from N, O; Ra means H, C1-6alkyl; Rb means H, C1-6alkyl; OH; Rc and Rd each independently means H, C1-6alkyl; Or one of R2 and R3 together with one of Ra and Rb and atoms whereto attached can form penta- or hexamerous ring, optionally with additional heteroatom chosen from O, N; or one of R2 and R3 together with one of Rc and Rd together with atoms whereto attached, can form tetra-hexamerous ring, optinally with additional heteroatom chosen from O, N; Rc means H, C1-6alkyl; provided when p =1, Ra, Rb, Rc and Rd mean H, Ar means indole-1-yl and R1 means C6H5, then R2 and R3 do not mean CH3 and do not form hexamerous ring, and when Ar means indole-3-yl, p =1, Ra, Rb, Rc and Rd means H and R1 means C6H5-, 3-OCH3C6H5- then R2 and R3 do not mean simultaneously H, and when p =1, Ra, Rb, Rc and Rd mean H, Ar means indolyl and R1 means thienyl, pyridinyl, quinolinyl, then one of R2 and R3 means H, and another means C1-6alkyl where possible substitutes are presented in cl.1 of.

EFFECT: compounds express activity of double inhibition serotonin reuptake, possibility to use thereof in making a pharmaceutical composition and a medical product.

32 cl, 7 tbl, 16 ex

FIELD: chemistry.

SUBSTANCE: invention relates to formula compounds, as well as their pharmaceutically acceptable salts, a pharmaceutical composition based on them, with inhibitory activity towards phosphorylation of protein Tau, and to methods of producing said compounds. In formula (I), R5 is aryl, aryl(C1-C6)alkyl; R6 is halogen; R3 is (C1-C6)alkyl, possibly substituted with substitutes selected from halogen, OH, NH2, azetidine; or monocyclic aryl or heteroaryl, such as thiophene or pyridine, possibly substituted with substitutes selected from NO2, CN, (C1-C6)alkoxy, (C1-C6)alkyl; or CONR1R2, SO2Ra, C(=NH)R1b, COOR1c; R1, R2 independently represent a hydrogen atom, possibly substituted with one halogen atom, (C1-C6)alkyl, moncyclic aryl or monocyclic 5- or 6-member heteroaryl containing 1 or 2 heteroatoms, such as S, O, N, possibly substituted with one or more substitutes selected from halogen, (C1-C6)alkyl, (C1-C6)alkoxyl, trifluoromethyl, N(CH3)2; or R1 and R2 can form a 5- or 6-member ring which optionally contains a heteroatom such as N; R1a is aryl, possibly substituted with (C1-C6)alkoxy; R1b is (C1-C6)alkyl, possibly substituted aryl or 6-member heteroaryl, containing 1 or 2 N atoms, where the substitute is (C1-C6)alkoxyl; R1c is (C1-C6)alkyl, (C2-C6)alkenyl; and their pharmaceutically acceptable salts.

EFFECT: aminoindazole derivatives as kinase inhibitor.

8 cl, 44 ex

FIELD: medicine.

SUBSTANCE: invention is related to new derivatives of benzoindazole of formula I , where radicals A1, A2, A3, R1, R2, R3, R4 and n have values mentioned in formula of invention, and their pharmaceutically acceptable salts, and also to application of these compounds for production of medicinal agent intended for modulation of α2-subsort of GABA receptor, and pharmaceutical composition that contains it.

EFFECT: application of compounds for preparation of medicinal agent intended for treatment of depression, disorder in the form of anxiety, psychic disorder, disturbed ability to learning and cognition, sleep disturbance, disorder in the form of cramps or fits or pain.

16 cl, 5 tbl, 40 ex

FIELD: chemistry.

SUBSTANCE: invention relates to new substituted 2-thiocarbamoyl-3-phenyl-3,3a,4,5,6,7-hexahydro-2N-indazoles with general formula I

, where R1=CH3, R2=H, CH3, R1+R2=(CH2)m, m=2-5; X=CkH2k+1 k=1-4, Hal, NO2, CkF2k+1 n=1-5; R3=CH3, Alk, Ar, and method of producing them, the first of which involves condensation of 2-arylidenecyclohexanones II with thiosemicarbazides III in aliphatic alcohol in the presence of acid as catalyst while heating (mainly 3,3a-cis-2-thiocarbamoyl-3-phenyl-3,3a,4,5,6,7-hexahydro-2N-indazoles of formula I are obtained using this method); in the second method, through condensation of 2-arylidenecyclohexanones II with hydrazine hydrate while boiling in aliphatic alcohol, intermediate N-unsubstituted hexahydroindazoles IV are obtained, which are acylated with alkyl- or arylisothiocyanates in an inert solvent in the presence of a base catalyst at room temperature (mainly 3,3a-trans-2-thiocarbamoyl-3-phenyl-3,3a,4,5,6,7-hexahydro-2N-indazoles of formula I are obtained using this method).

EFFECT: invention relates to a fungicide composition which contains substituted 2-thiocarbamoyl-3-phenyl-3,3a,4,5,6,7-hexahydro-2N-indazoles with general formula I, for example, 7-methyl- or 7,7-dimethyl-3-(4-chlorobenzylidene)-3,3a,4,5,6,7-hexahydro-2N-indazoles, which exhibits fungitoxicity higher than standard triadimefon.

4 cl, 5 tbl, 5 ex

FIELD: chemistry.

SUBSTANCE: present invention relates to phenyl substituted pyrrolidones of formula: , where R1 and R5 represent substitutes, which are independently chosen from a group which contains H, CN, halogen, C1-C4alkyl and OR8, where R8 represents C1-C4alkyl, R2 and R4 represent substitutes, which are chosen from a group which contains H, halogen, CN and C1-C4alkyl, R3 represents H, R6 represents a condensed phenyl heterocyclic ring system, chosen from , where R16 represents a substitute, chosen from a group which contains H, C(O)NR18R19 and S(O)2R20, where R18 and R19 represent H or C1-C6alkyl; R20 represents C1-C6alkyl or phenyl; and R17 represents a substitute, which is chosen from a group which contains H, NH2, (CH2)mOH, C(O)NR21R22, SO2R23 and NHSO2R23; where R21 and R22 represent substitutes, which are independently chosen from a group which contains H and substituted or unsubstituted C1-C6alkyl, or, together with a nitrogen atom to which they are bonded, optionally form a ring; R23 represents C1-C6alkyl; and m equals 1; or R6 represents a group, where R9 and R11 represent substitutes, which are independently chosen from a group which contains H, halogen, CN, C(O)NR12R12, NR12R12 and OR12, where each R12 represents H or C1-C4alkyl, and under the condition that, at least one of substitutes R9 and R11 is not hydrogen; R10 represents CN, NR13R14, SO2NHR13, NHSO2R13, O(CH2)nSO2R15, SO2R15, SO2(CH2)nNR13R14 or C(O)NR13R14, where R13 and R14 represent H or C1-C4alkyl; R15 represents C1-C4alkyl, n equals 1-2, and R7 represents halogen, C1-C4alkyl, C2-C4alkenyl or C2-C4alkynyl.

EFFECT: design of compounds and a pharmaceutical composition for inhibiting HIV growth.

19 cl, 12 ex, 1 tbl

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to medicine. Described is preparative form for transcutaneous introduction, which makes possible stable introduction of medication against dementia for a long period of time. Preparative form for transcutaneous introduction of medication against dementia, which is used as plaster on skin, contains, at least, one adhesive layer, intermediate membrane and layer, which is reservoir of medication, successively, from the side, which is stuck on skin, where layer, which is reservoir of medication, contains, at least, one medication against dementia, aminated polymer, polyatomic alcohol and one or several esters of carboxylic acids.

EFFECT: intermediate membrane makes possible controlled penetration of medication against dementia towards skin, adhesive layer makes it possible to stick preparative form for transcutaneous introduction on skin and is permeable for medication against dementia.

9 cl, 4 dwg, 1 tbl, 6 ex

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