New compounds

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to a compound of formula or to its pharmaceutically acceptable salts wherein -A-(R1)a means a group; -B-(R2)b means a group specified in the patent claim 1, R3 means hydrogen; X means CH2 or O; and Y means CH2. Also, the invention refers to a pharmaceutical composition exhibiting FGFR inhibitor activity on the basis of the declared compound.

EFFECT: there are produced new compounds and based pharmaceutical composition which can find application in medicine for preparing a cancer drug.

8 cl, 1 tbl, 180 ex

 

The text descriptions are given in facsimile form.

1. The compound of formula (I):

or its pharmaceutically acceptable salt
where-A-(R1)ameansgroup;
-B-(R2)bmeans;;;
;;;
;;;
;;;
;;;
;;;
;;;;
;;;
;;;
;;;
;;;
;;;
;;;
;;;
;;;
;;;
;;;
;;;
;;;
;;;
;;;
;;;
;;;
;;;
;;or
group;
R3means hydrogen;
X is CH2or About; and
Y represents CH2.

2. The compound of formula (I) or its pharmaceutically acceptable salt according to claim 1
where-A-(R )ameansgroup;
-B-(R2)bmeans;;;;;;
;;;
;;;
;;;
;;
or
group;
R3means hydrogen;
X is CH2or About; and
Y represents CH2.

3. The compound of formula (I) according to claim 1, where the compound is selected from
N-[5-[2-(3,5-acid)ethyl]-2H-pyrazole-3-yl]benzamide,
N-[5-[2-(3,5-acid)ethyl]-2H-pyrazole-3-yl]-4-methoxy-benzamide,
N-[5-[2-(3,5-acid)ethyl]-2H-pyrazole-3-yl]-4-morpholine-4-yl-benzamide,
N-[5-[2-(3,5-acid)ethyl]-2H-pyrazole-3-yl]-4-(4-methylpiperazin-1-yl)benzamide,
N-[5-[(3,5-acid)methoxy]-2H-pyrazole-3-yl]-4-(4-methylpiperazin-1-yl)benzamide,
N-[5-[(3,5-acid)methoxy]-2H-pyrazole-3-yl]-5-(4-methylpiperazin-1-yl)pyrazin-2-carboxamide,
N-[5-[2-(3,5-acid)ethyl]-1H-pyrazole-3-yl]-4-(2-ethoxyethoxy)benzamide,
N-[5-[2-(3,5-acid)ethyl]-1H-pyrazole-3-yl]-4-(1-piperidyl)benzamide,
N-[5-[2-(3,5-acid)ethyl]-1H-pyrazole-3-yl]-4-piperazine-1-yl-benzamide,
N-[5-[2-(3,5-acid)ethyl]-1H-pyrazole-3-yl]-4-(dimethylaminomethyl)benzamide,
N-[5-[2-(3,5-acid)ethyl]-1H-pyrazole-3-yl]-4-[(3,3-dimethyl-1-piperidyl)methyl]benzamide,
N-[5-[2-(3,5-acid)ethyl]-1H-pyrazole-3-yl]-4-(2-morpholine-4-retil)benzamide,
N-[5-[2-(3,5-acid)ethyl]-1H-pyrazole-3-yl]-4-[(methyl-(oxolan-2-ylmethyl)amino)methyl]benzamide,
N-[5-[2-(3,5-acid)ethyl]-1H-pyrazole-3-yl]-4-(4-piperidyl)benzamide,
N-[5-[2-(3,5-acid)ethyl]-1H-pyrazole-3-yl]-4-dimethylamino-benzamide,
N-[5-[2-(3,5-acid)ethyl]-1H-pyrazole-3-yl]-5-piperazine-1-yl-thiophene-2-carboxamide,
N-[5-[(3,5-acid)methoxy]-2H-pyrazole-3-yl]-5-(4-methylpiperazin-1-yl)pyridine-2-carboxamide,
N-[5-[(3,5-acid)methoxy]-2H-pyrazole-3-yl]-4-(2-diethylaminoethylamine)benzamide,
N-[5-[(3,5-acid)methoxy]-2H-pyrazole-3-yl]-4-methoxy-benzamide,
N-[5-[(3,5-acid)methoxy]-1H-pyrazole-3-yl]-2-(4-methylpiperazin-1-yl)pyrimidine-5-carboxamide,
4-(1,4-diazepan-1-yl)-N-[5-[(3,5-acid)methoxy]-1H-pyrazole-3-yl]benzamide,
N-[5-[2-(2,5-acid)ethyl]-2H-pyrazole-3-yl]-4-(4-methylpiperazin-1-yl)benzamide,
N-[5-[2-(3,5-acid)ethyl]-2H-pyrazole-3-yl]-4-(3,5-dimethylpiperazine-1-yl)benzamide,
N-[5-[2-(3,5-acid)ethyl]-2H-pyrazole-3-yl]-2-(4-methylpiperazin-1-yl)pyrimidine-5-carboxamide,
N-[5[2-(3,5-acid)ethyl]-1H-pyrazole-3-yl]-4-(4-propan-2-reparation-1-yl)benzamide,
4-(4-cyclopropylmethyl-1-yl)-N-[5-[2-(3,5-acid)ethyl]-1H-pyrazole-3-yl]benzamide,
4-(4-cyclobutylmethyl-1-yl)-N-[5-[2-(3,5-acid)ethyl]-1H-pyrazole-3-yl]benzamide,
N-[5-[2-(3-methoxyphenyl)ethyl]-1H-pyrazole-3-yl]-4-(4-methylsulfonylmethane-1-yl)benzamide,
N-[5-[2-(3,5-acid)ethyl]-1H-pyrazole-3-yl]-4-(1-methyl-4-piperidyl)benzamide,
4-(3,4,6,7,8,8A-hexahydro-1H-pyrrolo[2,1-C]pyrazin-2-yl)-N-[5-[2-(3,5-acid)ethyl]-2H-pyrazole-3-yl]benzamide,
4-(1,3,4,6,7,8,9,9a-octahedrite[2,1-C]pyrazin-2-yl)-N-[5-[2-(3,5-acid)ethyl]-2H-pyrazole-3-yl]benzamide,
N-[5-[2-(3,5-acid)ethyl]-1H-pyrazole-3-yl]-4-(3,4-dimethylpiperazine-1-yl)benzamide,
N-[5-[2-(3,5-acid)ethyl]-1H-pyrazole-3-yl]-4-(3,4,5-trimethylpyrazine-1-yl)benzamide,
N-[5-[(3,5-acid)methoxy]-2H-pyrazole-3-yl]-5-(3,4-dimethylpiperazine-1-yl)thiophene-2-carboxamide,
4-(1,3,4,6,7,8,9,9a-octahedrite[2,1-C]pyrazin-2-yl)-N-[5-[(3,5-acid)methoxy]-2H-pyrazole-3-yl]benzamide,
4-(1-cyclopropylidene-4-yl)-N-[5-[2-(3,5-acid)ethyl]-2H-pyrazole-3-yl]benzamide,
N-[5-[(3,5-acid)methoxy]-2H-pyrazole-3-yl]-4-[(3R,5S) - for 3,5-dimethylpiperazine-1-yl]benzamide,
N-[5-[(3,5-acid)methoxy]-2H-pyrazole-3-yl]-4-(3,4-dimethylpiperazine-1-yl)benzamide,
N-[5-[(3,5-acid)methoxy]-2H-pyrazole-3-yl]-4-(1-methylpiperidin-4-yl)benzamide,
4-(3,4,6,7,8,8A-hexahydro-1H-pyrrolo[2,1-C]pyrazin-2-yl)-N-[5-[(3,5-dimethoxy the Nile)methoxy]-2H-pyrazole-3-yl]benzamide,
5-(1,3,4,6,7,8,9,9a-octahedrite[2,1-C]pyrazin-2-yl)-N-[5-[2-(3,5-acid)ethyl]-2H-pyrazole-3-yl]pyrazin-2-carboxamide,
N-[5-[2-(3,5-acid)ethyl]-2H-pyrazole-3-yl]-5-(4-methylpiperazin-1-yl)thiophene-2-carboxamide,
N-[5-[(3,5-acid)methoxy]-2H-pyrazole-3-yl]-5-(4-methylpiperazin-1-yl)thiophene-2-carboxamide,
N-[5-[2-(3,5-acid)ethyl]-2H-pyrazole-3-yl]-5-(3,3-dimethylpiperidin-1-yl)pyrazin-2-carboxamide,
5-(4-cyclopropylmethyl-1-yl)-N-[5-[(3,5-acid)methoxy]-2H-pyrazole-3-yl]pyrazin-2-carboxamide,
N-[5-[(3,5-acid)methoxy]-2H-pyrazole-3-yl]-4-[(3R,5S)-3,4,5-trimethylpyrazine-1-yl]benzamide,
N-[5-[(3,5-acid)methoxy]-2H-pyrazole-3-yl]-4-(3,3-dimethylpiperidin-1-yl)benzamide,
N-[5-[2-(3,5-acid)ethyl]-2H-pyrazole-3-yl]-5-[(3R,5S) - for 3,5-dimethylpiperazine-1-yl]pyrazin-2-carboxamide,
5-(4-cyclopropylmethyl-1-yl)-N-[5-[2-(3,5-acid)ethyl]-2H-pyrazole-3-yl]pyrazin-2-carboxamide,
5-(3,4,6,7,8,8A-hexahydro-1H-pyrrolo[2,1-C]pyrazin-2-yl)-N-[5-[2-(3,5-acid)ethyl]-2H-pyrazole-3-yl]pyrazin-2-carboxamide,
5-(1,3,4,6,7,8,9,9a-octahedrite[2,1-C]pyrazin-2-yl)-N-[5-[(3,5-acid)methoxy]-2H-pyrazole-3-yl]pyrazin-2-carboxamide,
4-(4-cyclopropylmethyl-1-yl)-N-[5-[(3,5-acid)methoxy]-2H-pyrazole-3-yl]benzamide,
4-(4-cyclobutylmethyl-1-yl)-N-[5-[(3,5-acid)methoxy]-2H-pyrazole-3-yl]benzamide,
2-(1,3,4,6,7,8,9,9a-octahedrite[2,1-C]feast the Jn-2-yl)-N-[5-[(3,5-acid)methoxy]-2H-pyrazole-3-yl]pyrimidine-5-carboxamide,
5-(3,4,6,7,8,8A-hexahydro-1H-pyrrolo[2,1-C]pyrazin-2-yl)-N-[5-[2-(3,5-acid)ethyl]-2H-pyrazole-3-yl]thiophene-2-carboxamide,
5-(3,4,6,7,8,8A-hexahydro-1H-pyrrolo[2,1-C]pyrazin-2-yl)-N-[5-[(3,5-acid)methoxy]-2H-pyrazole-3-yl]thiophene-2-carboxamide,
5-(3,4,6,7,8,8A-hexahydro-1H-pyrrolo[2,1-C]pyrazin-2-yl)-N-[5-[(3,5-acid)methoxy]-2H-pyrazole-3-yl]pyrazin-2-carboxamide,
N-[5-[2-(3,5-acid)ethyl]-2H-pyrazole-3-yl]-5-(3,4-dimethylpiperazine-1-yl)pyrazin-2-carboxamide,
N-[5-[(3,5-acid)methoxy]-2H-pyrazole-3-yl]-5-(3,4-dimethylpiperazine-1-yl)pyrazin-2-carboxamide,
N-[5-[2-(3,5-acid)ethyl]-2H-pyrazole-3-yl]-5-[(3R,5S)-3,4,5-trimethylpyrazine-1-yl]pyrazin-2-carboxamide,
2-(4-cyclopropylmethyl-1-yl)-N-[5-[2-(3,5-acid)ethyl]-2H-pyrazole-3-yl]pyrimidine-5-carboxamide,
2-(1,3,4,6,7,8,9,9a-octahedrite[2,1-C]pyrazin-2-yl)-N-[5-[2-(3,5-acid)ethyl]-2H-pyrazole-3-yl]pyrimidine-5-carboxamide,
2-(3,4,6,7,8,8A-hexahydro-1H-pyrrolo[2,1-C]pyrazin-2-yl)-N-[5-[2-(3,5-acid)ethyl]-2H-pyrazole-3-yl]pyrimidine-5-carboxamide,
5-[(3R,5S)-4-(cyanomethyl)for 3,5-dimethylpiperazine-1-yl]-N-[5-[2-(3,5-acid)ethyl]-2H-pyrazole-3-yl]pyrazin-2-carboxamide,
N-[5-[(3,5-acid)methoxy]-2H-pyrazole-3-yl]-5-[(3R,5S)-3,4,5-trimethylpyrazine-1-yl]pyrazin-2-carboxamide,
5-[(3R,5S)-4-(cyanomethyl)for 3,5-dimethylpiperazine-1-yl]-N-[5-[(3,5-acid)methoxy]-2H-pyrazole-3-yl]pyrazin-2-carboxamide,
N-[5-[(3,5-acid)methoxy]-2H-pyrazole-3-yl]-2-(3,4-dimethylpiperazine-1-yl)pyrimidine-5-carboxamide,
2-(4-cyclopropylmethyl-1-yl)-N-[5-[(3,5-acid)methoxy]-2H-pyrazole-3-yl]pyrimidine-5-carboxamide,
2-(3,4,6,7,8,8A-hexahydro-1H-pyrrolo[2,1-C]pyrazin-2-yl)-N-[5-[(3,5-acid)methoxy]-2H-pyrazole-3-yl]pyrimidine-5-carboxamide,
N-[5-[2-(3,5-acid)ethyl]-2H-pyrazole-3-yl]-2-(3,4-dimethylpiperazine-1-yl)pyrimidine-5-carboxamide,
N-[5-[2-(3,5-acid)ethyl]-2H-pyrazole-3-yl]-2-[(3R,5S)-3,4,5-trimethylpyrazine-1-yl]pyrimidine-5-carboxamide,
N-[5-[2-(3,5-acid)ethyl]-2H-pyrazole-3-yl]-4-[4-(1-hydroxypropan-2-yl)piperazine-1-yl]benzamide,
N-(3-(3,5-dimethoxybenzyl)-1H-pyrazole-5-yl)-2-((3R,5S)-3,4,5-trimethylpyrazine-1-yl)pyrimidine-5-carboxamide,
N-[5-[2-(3,5-acid)ethyl]-2H-pyrazole-3-yl]-4-(3,3-dimethylpiperidin-1-yl)benzamide,
N-[5-[(3,5-acid)methoxy]-2H-pyrazole-3-yl]-5-(3,3-dimethylpiperidin-1-yl)thiophene-2-carboxamide,
N-[5-[(3,5-acid)methoxy]-2H-pyrazole-3-yl]-5-(4-ethylpiperazin-1-yl)thiophene-2-carboxamide,
N-[5-[2-(3,5-acid)ethyl]-2H-pyrazole-3-yl]-5-(4-methyl-1,4-diazepan-1-yl)thiophene-2-carboxamide,
N-[5-[2-(3,5-acid)ethyl]-2H-pyrazole-3-yl]-2-(4-ethyl-3-methylpiperazin-1-yl)pyrimidine-5-carboxamide,
N-[5-[2-(3,5-acid)ethyl]-2H-pyrazole-3-yl]-4-(1-prop-2-rilpivirine-4-yl)benzamide,
4-(1,4-diazepan-1-yl)-N-[5-[2-(3,5-acid)this is l]-2H-pyrazole-3-yl]benzamide,
N-[5-[2-(3,5-acid)ethyl]-2H-pyrazole-3-yl]-4-(1-prop-2-vinylpyridin-4-yl)benzamide,
N-[5-[(3,5-acid)methoxy]-2H-pyrazole-3-yl]-5-[(3S,5R) - for 3,5-dimethylpiperazine-1-yl]thiophene-2-carboxamide,
N-[5-[2-(3,5-acid)ethyl]-2H-pyrazole-3-yl]-4-[1-(2-methoxyethyl)piperidine-4-yl]benzamide,
N-[5-[2-(3,5-acid)ethyl]-2H-pyrazole-3-yl]-5-(1-methylpiperidin-4-yl)pyrazin-2-carboxamide,
N-[5-[2-(3,5-acid)ethyl]-2H-pyrazole-3-yl]-5-(1-methyl-3,6-dihydro-2H-pyridine-4-yl)pyrazin-2-carboxamide,
N-[5-[2-(3,5-acid)ethyl]-2H-pyrazole-3-yl]-4-[(3R,5S) - for 3,5-dimethylpiperazine-1-yl]benzamide,
N-[5-[2-(3,5-acid)ethyl]-2H-pyrazole-3-yl]-4-[(3R,5S)-3,4,5-trimethylpyrazine-1-yl]benzamide,
N-[5-[2-(3,5-acid)ethyl]-2H-pyrazole-3-yl]-4-(4-methyl-1,4-diazepan-1-yl)benzamide,
N-[5-[2-(3,5-acid)ethyl]-2H-pyrazole-3-yl]-5-(3-dimethylaminopropan-1-yl)pyrazin-2-carboxamide,
5-(3-diethylaminopropyl-1-yl)-N-[5-[2-(3,5-acid)ethyl]-2H-pyrazole-3-yl]pyrazin-2-carboxamide,
N-[5-[2-(3,5-acid)ethyl]-2H-pyrazole-3-yl]-4-(1-ethylpiperazin-4-yl)benzamide,
N-[5-[2-(3,5-acid)ethyl]-2H-pyrazole-3-yl]-5-(3-methylaminopropyl-1-yl)pyrazin-2-carboxamide,
N-[5-[2-(3,5-acid)ethyl]-2H-pyrazole-3-yl]-2-(1-methylpiperidin-4-yl)pyrimidine-5-carboxamide,
N-[5-[2-(3,5-acid)ethyl]-2H-pyrazole-3-yl]-5-(4-methyl-1,4-diazepan-1-yl)pyrazin-2-carboxamide,
N-[5-[2-(3,5-acid)is Tyl]-2H-pyrazole-3-yl]-4-(4-prop-2-enyl-1,4-diazepan-1-yl)benzamide,
4-(4-cyclopropyl-1,4-diazepan-1-yl)-N-[5-[2-(3,5-acid)ethyl]-2H-pyrazole-3-yl]benzamide,
N-[5-[2-(3,5-acid)ethyl]-2H-pyrazole-3-yl]-4-(4-propan-2-yl-1,4-diazepan-1-yl)benzamide,
N-[5-[2-(3,5-acid)ethyl]-2H-pyrazole-3-yl]-5-(4-propan-2-yl-1,4-diazepan-1-yl)pyrazin-2-carboxamide,
N-[5-[2-(3,5-acid)ethyl]-2H-pyrazole-3-yl]-5-(4-propan-2-yl-1,4-diazepan-1-yl)thiophene-2-carboxamide,
N-[5-[2-(3,5-acid)ethyl]-2H-pyrazole-3-yl]-5-(4-ethyl-1,4-diazepan-1-yl)pyrazin-2-carboxamide,
N-[5-[2-(3,5-acid)ethyl]-2H-pyrazole-3-yl]-4-(4-ethyl-1,4-diazepan-1-yl)benzamide,
N-[5-[2-(3,5-acid)ethyl]-2H-pyrazole-3-yl]-2-(4-ethyl-1,4-diazepan-1-yl)pyrimidine-5-carboxamide,
N-[5-[2-(3,5-acid)ethyl]-2H-pyrazole-3-yl]-5-(4-prop-2-enyl-1,4-diazepan-1-yl)pyrazin-2-carboxamide,
N-[5-[2-(3,5-acid)ethyl]-2H-pyrazole-3-yl]-2-(4-propan-2-yl-1,4-diazepan-1-yl)pyrimidine-5-carboxamide,
5-(4-cyclopropyl-1,4-diazepan-1-yl)-N-[5-[2-(3,5-acid)ethyl]-2H-pyrazole-3-yl]pyrazin-2-carboxamide,
N-[5-[2-(3,5-acid)ethyl]-2H-pyrazole-3-yl]-2-(4-prop-2-enyl-1,4-diazepan-1-yl)pyrimidine-5-carboxamide,
N-[5-[2-(3,5-acid)ethyl]-2H-pyrazole-3-yl]-2-(4-methyl-1,4-diazepan-1-yl)pyrimidine-5-carboxamide,
2-(4-cyclopropyl-1,4-diazepan-1-yl)-N-[5-[2-(3,5-acid)ethyl]-2H-pyrazole-3-yl]pyrimidine-5-carboxamide,
N-[5-[(3,5-acid)methoxy]-2H-pyrazole-3-yl]-4-(4-ethylpiperazin-1-yl)benzamide, N-[5-[2-(3,5-acid)ethyl]-2H-pyrazole-3-yl]-4-(4-ethylpiperazin-1-yl)benzamide,
and pharmaceutically acceptable salts of any one of the listed compounds.

4. The compound of formula (I) according to claim 1, where the compound is a N-[5-[2-(3,5-acid)ethyl]-2H-pyrazole-3-yl]-4-[(3R,5S) - for 3,5-dimethylpiperazine-1-yl)benzamide.

5. The compound of formula (I) according to claim 1, where the compound is a N-[5-[2-(3,5-acid)ethyl]-1H-pyrazole-3-yl]-4-(3,4-dimethylpiperazine-1-yl)benzamide.

6. The use of the compounds of formula (I) or pharmaceutically acceptable salt according to claim 1 in the manufacture of a medicinal product intended for receiving FGFR inhibitory effect.

7. The compound of formula (I) or its pharmaceutically acceptable salt according to claim 1 having activity as an inhibitor of FGFR.

8. Pharmaceutical composition having activity as an inhibitor of FGFR, comprising a compound of formula (I) or its pharmaceutically acceptable salt according to claim 1 together with a pharmaceutically acceptable adjuvant, diluent or carrier.



 

Same patents:

FIELD: medicine, pharmaceutics.

SUBSTANCE: pyrazolo[1,5-a]-pyrimidine compounds according to the invention are specified in a group consisting of: N-{2-fluor-5-[3-nitro-pyrazolo[1,5-a]pyrimidin-7-yl]-phenyl}-N-methylacetamide, N-{2-fluor-5-[3-cyano-pyrazolo[1,5-a]pyrimidin-7-yl]-phenyl}-N-methylacetamide, N-{2-chlor-5-[3-nitro-pyrazolo[1,5-a]pyrimidin-7-yl]-phenyl}-N-methylacetamide, N-{2-chlor-5-[3-cyano-pyrazolo[1,5-a]pyrimidin-7-yl]-phenyl}-N-methylacetamide, N-{2-fluor-5-[3-nitro-pyrazolo[1,5-a]pyrimidin-7-yl]-phenyl}-N-ethylmethanesulphonamide; {2-fluor-5-[3-cyano-pyrazolo[1,5-a]pyrimidin-7-yl]-phenyl}-N-methylmethanesulphonamide, N-{2-chlor-5-[3-nitro-pyrazolo[1,5-a]pyrimidin-7-yl]-phenyl}-N-methylmethanesulphonamide, N-{2-chlor-5-[3-cyano-pyrazolo[1,5-a]pyrimidin-7-yl]-phenyl}-N-methylmethanesulphonamide, N-{2-fluor-5-[3-cyano-2-methyl-pyrazolo[1,5-a]pyrimidin-7-yl]-phenyl}-N-methylacetamide, N-{2-chlor-5-[3-cyano-2-methyl-pyrazolo[1,5-a]pyrimidin-7-yl]-phenyl}-N-methylacetamide, N-{2-fluor-5-[3-cyano-2-methyl-pyrazolo[1,5-a]pyrimidin-7-yl]-phenyl}-N-methyl-methanesulphonamide, N-{2-chlor-5-[3-cyano-2-methyl-pyrazolo[1,5-a]pyrimidin-7-yl]-phenyl}-N-methyl-methanesulphonamide, N-{2-methyl-5-[3-(thiophene-2-carbonyl)-pyrazolo[1,5-a]pyrimidin-7-yl]-phenyl}-N-methylacetamide, N-{2-methoxy-5-[3-(thiophene-2-carbonyl)-pyrazolo[1,5-a]pyrimidin-7-yl]-phenyl}-N-methylacetamide, N-{2,4-difluor-5-[3-(thiophene_2-carbonyl)-pyrazolo[1,5-a]pyrimidin-7-yl]-phenyl}-N-methylacetamide and N-{5-fluor-2-methoxy-3-[3-(thiophene-2-carbonyl)-pyrazolo[1,5-a]pyrimidin-7-yl]-phenyl}-N-methylacetamide.

EFFECT: preparing pyrazolo[1,5-a]pyrimidine compounds, their pharmaceutically acceptable salts and hydrates showing an ability to inhibit GABAA receptors, and applicable for treating and preventing anxiety, epilepsy and sleeping disorders, including insomnia, as well as for inducing a sedative-hypnotic, analgesic and sleeping effects and myorelaxation.

14 cl, 6 tbl, 4 dwg, 22 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: there are described new compounds of general formula (I):

in the form of a separate stereoisomer or mixed stereoisomers or in the form of its pharmaceutically acceptable salt wherein R1 is indazolyl or substituted indazolyl; R6 is C6aryl or C6-12aryl substituted by halogen, hydroxy, cyano and C1-6alkoxy; or C6heterocyclyl containing 1-2 heteroatoms specified in nitrogen or oxygen; each X2 and X3 independently mean hydrogen, hydroxy or phosphate.

EFFECT: prepared compounds may be used for preparing a drug preparation for treating or preventing cancer, particularly acute myeloid leukemia.

6 cl, 6 tbl, 8 ex, 4 dwg

FIELD: chemistry.

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

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

16 cl, 479 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: present patent claim discloses sulphonyl-substituted compounds of formula QUIN which are used for the purpose of a method for producing a macrocyclic compound of formula (I)

EFFECT: compounds of formula (I) are effective active agents for treating Hepatitis C viral (HCV) infection.

8 cl, 1 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to 4-amino-3-arylamino-6-arylpyrazolol[3.4-d]-pyrimidine derivatives showing antiviral activity. In formula I: the groups A and B independently represent phenyl, naphthyl, pyridyl, quinolyl, pyrazinyl, pyrimidyl, pyrazolyl, triazinyl, imidazolyl, furanyl, thienyl, and in each of these groups one to three hydrogen atoms can be independently substituted by the radical R1; R1 can be NO2, CN, CONR22, COOR2, CHO, CONH2, halogen, saturated or unsaturated, linear or branched alkyl with a number of atoms in the chain 1 to 7, saturated or unsaturated, linear or branched alkanole with a number of atoms in the chain 1 to 8, OR2, SR2, NR22, SO2NR32, di- or trifluoromethyl, phenyl; R2 represents hydrogen, CF3, and linear or branched alkyl with a number of atoms in the chain 1 to 7; the radical R3 represents H, benzyl, or linear or branched alkyl with a number of atoms in the chain 1 to 7; the radicals R4 and R5 represent hydrogen.

EFFECT: developing the method for preparing the compound of formula (I) and applying the compounds of the present invention as a biological agent exhibiting antiviral activity, eg for treating picornavirus infections.

9 cl, 6 ex, 1 dwg

FIELD: chemistry.

SUBSTANCE: described are novel benzotriazole UV-absorbers, having absorption spectrum shifted towards the long-wave side with considerable absorption in the region up to 410-420 nm, having general formulae (a)-(k) (structural formula and values of radicals are given in the description), composition which is stabilised with respect to UV radiation and containing novel UV-absorbers, and use of the novel compounds as UV light stabilisers for organic materials.

EFFECT: obtaining novel benzotriazole UV-absorbers, having absorption spectrum shifted towards the long-wave side.

13 cl, 23 ex, 2 tbl

FIELD: chemistry.

SUBSTANCE: described is a novel compound - 6-(2'-amino-2'-carboxyethylthio)-2-methylthio-4-pivaloyloxy-methyl-1,2,4-triazolo[5,1-c] 1,2,4-triazin-7(4H)-one of formula having antiviral action and low toxicity.

EFFECT: compound can be used in medicine.

1 cl, 1 ex, 3 dwg

FIELD: chemistry.

SUBSTANCE: invention relates to organic chemistry and synthesis of heterocyclic compounds - 5,6-dihydro-7H-pyrrolo[1,2-d][1,4]benzodiazepin-6-one derivatives of formula 1a-e by boiling 2-amino-N-(2-furan-2-yl-phenyl)-acetamides in a mixture of glacial acetic acid and concentrated hydrochloric acid with subsequent treatment with sodium bicarbonate while boiling.

EFFECT: method is characterised by simple execution.

2 tbl, 5 ex

Polycyclic compound // 2451685

FIELD: medicine, pharmaceutics.

SUBSTANCE: described is a new polycyclic compound with general formula (I-1) and (1-3) or a pharmaceutically acceptable salt thereof where X1- -CR1 =CR2 - where R1 and R2 independently stand for hydrogen or C1-6 alkyl while Het stands for a radical of the following formulae: that may be substituted 1-3 times additionally described is a pharmaceutical composition containing such compound and intended for prevention or treatment of diseases caused by β-amyloid.

EFFECT: production of a pharmaceutical composition prevention or treatment of diseases caused by β-amyloid.

7 cl, 392 ex, 12 tbl

FIELD: medicine, pharmaceutics.

SUBSTANCE: this invention relates to compounds that may be applied for HIV infection treatment or prevention or for AIDS or AIDS-associated complex treatment. According to the invention, the compounds represent compounds with formula I, where A stands for A1 , A2 , A3 or A4 and R1, R2, R3, R4a, R4b, R5, R6, Ar, X1, X2, X4, X4 and X5 having values specified in the patent claim. Additionally, this invention relates to a pharmaceutical composition containing the said compounds.

EFFECT: production of compounds possessing inhibition activity with regard to HIV reverse transcriptase.

22 cl, 3 tbl, 29 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to to new compounds of formula (1) or their pharmaceutically acceptable salts, optionally in the form of (1S)-isomers showing the properties of polo-like kinase (serine-threonine kinase) PLK1 inhibitor. In the compounds of formula (1) , R1 represents a halogen atom; a lower alkyl group having 1-2 carbon atoms, which can be substituted by 3 fluorine atoms; or a cyclopropyl group; R2 represents a hydrogen atom; one of R3 and R4 represents a hydrogen atom while the other one of R3 and R4 represents: a) a lower alkyl group substituted by NRaRb wherein each Ra and Rb, which can be identical or different, represent a lower alkyl group, or each Ra and Rb, which can be different, represent a hydrogen atom, a lower alkyl group or a cycloalkyl group having 3-6 carbon atoms wherein a cycloalkyl group can be substituted by one ore more substitutes which can be identical or different and specified in a group 1): a lower alkyl; b) a 4-6-member aliphatic heterocyclic group specified in an azetidinyl group, a pyrrolidinyl group and a piperidinyl group; c) a lower alkyl group substituted by a 4-6-member aliphatic heterocyclic group specified in an azetidinyl group, a pyrrolidinyl group and a piperidinyl group; d) a 6-member aromatic heterocyclic group specified in a pyridyl group wherein each of an aliphatic heterocyclic group and an aromatic heterocyclic group can be substituted by substitutes specified in a group 1) described above; R5 represents a hydrogen atom, a cyano group, a halogen atom or a lower alkyl group.

EFFECT: compounds can find application in treating oncological diseases.

10 cl, 4 dwg, 8 tbl, 42 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: present invention refers to organic chemistry, namely new 1H-pyrrolo[3,4-b]quinoline-3,9(2H, 4H)-dione derivatives of general formula 1

wherein R1=Alk, Ar; R2=H, Alk, halogen; R3=H, Alk, halogen; R4=H, Alk, halogen; R5=H, Alk, halogen; R6=CH2Ar, R7=Ar, Also, the invention refers to a method for preparing them.

EFFECT: there are prepared new 1H-pyrrolo[3,4-b]quinoline-3,9(2H, 4H)-dione derivatives possessing anti-tuberculosis activity.

3 cl, 1 tbl, 9 ex

FIELD: chemistry.

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

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

16 cl, 479 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: present invention refers to new benzimidazole derivatives of general formula (I) or to its pharmacologically acceptable salts wherein R1 represents a C6-aryl group which can be substituted by 1-3 groups optionally specified in a group of substitutes (a), or a heterocyclic group which represents pyridyl, dihydrobenzofuranyl, 1,3-benzodioxolyl, tetrahydropyranyl, tetrahydrofuranyl which can be substituted by 1-3 groups optionally specified in a group of substitutes (a), R2 represents a C1-C6 alkyl group, R3 represents a C6-aryl group which can be substituted by 1-2 groups optionally specified in a group of substitutes (a), Q represents a group represented by formula =CH-, or a nitrogen atom and a group of substitutes (a) represents a group consisting of a halogen atom, a C1-C6 alkyl group, a C1-C6 halogenated alkyl group, a carboxyl group, a C2-C7 alkylcarbonyl group, a C2-C7 alkoxycarbonyl group, a C1-C6 alkoxy group, a C1-C6 halogenated alkoxy group, an amino group, a 4-morpholinyl group and a di-C1-C6 alkyl)amino group. Also, the invention refers to a pharmaceutical composition based on a compound of formula (I), to a PPARγ activator/modulator based on the compound of formula (I), to using the compound of formula (I), to a method of reducing blood glucose, to a method of activating PPARγ, a method of treating and/or preventing said pathological conditions.

EFFECT: there are produced new benzimidazole derivatives showing PPARγ modulatory activity.

41 cl, 2 dwg, 6 tbl, 76 ex

FIELD: chemistry.

SUBSTANCE: described are novel benzotriazole UV-absorbers, having absorption spectrum shifted towards the long-wave side with considerable absorption in the region up to 410-420 nm, having general formulae (a)-(k) (structural formula and values of radicals are given in the description), composition which is stabilised with respect to UV radiation and containing novel UV-absorbers, and use of the novel compounds as UV light stabilisers for organic materials.

EFFECT: obtaining novel benzotriazole UV-absorbers, having absorption spectrum shifted towards the long-wave side.

13 cl, 23 ex, 2 tbl

FIELD: chemistry.

SUBSTANCE: invention relates to novel azaindole derivatives, having JAK-2 and JAK-3 kinase inhibiting activity, or pharmaceutically acceptable salts thereof. In formula (I): R3 denotes H; X1 denotes N or CR4; R2 denotes H, COOH, COOR' or CONHR'; R4 denotes H, F, R, OH, OR', COR', COOH, COOR', CONH2 or CN; or R2 and R4, taken together, form a benzene ring optionally substituted with 1-2 R10; R' denotes C1-3-alkyl or C1-3-alkenyl, each optionally substituted 1-2 R5; each R5 is independently selected from CN, unsubstituted C1-2alkyl, or two groups R5 together with a carbon atom with which they are bonded form a cyclopropyl ring; each R10 is independently selected from halogen, OCH3 or OH; R1 denotes or , R is H or denotes C1-2alkyl, optionally substituted with 1-3 R11; R6 denotes C1-4alkyl, optionally substituted with 1-5 R12; values of radicals R7 -R9, ring A, R11 -R14. The invention also relates to a pharmaceutical composition containing said compounds and a method of treating or reducing severity of a pathological condition such as allergy, asthma, amyotrophic lateral sclerosis, multiocular sclerosis, graft rejection, rheumatoid arthritis, solid malignant tumour, haematologic malignant disease, leukaemia, lymphoma and myeloproliferative disorders.

EFFECT: high efficiency of using the compounds.

41 cl, 6 ex, 6 tbl

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of general formula , where R1 denotes OH, OPO3H2 or OCOR5; R2 denotes H, OH or OPO3H2; A denotes N or CR6; R3 denotes fluorine; R4 denotes H, C1-3alkyl or C3-6cycloalkyl; R5 denotes an alanine residue; R6 denotes H, C1-6alkoxy group or halogen; and n=0 or 1; and to pharmaceutically acceptable salts of compounds of formula I. The invention also relates to a pharmaceutical composition having antibacterial activity, and to use of compounds of formula I to obtain a medicinal agent for preventing or treating bacterial infections.

EFFECT: compounds of formula I, having antibacterial activity.

14 cl, 3 dwg, 2 tbl, 14 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a compound having chemical structure of formula II , all salts and stereoisomers thereof, where the value of radicals D, A2 and B are as described in paragraph 1 of the claim. The invention also relates to a composition having activity as a c-kit and c-fms modulator, a method of treating a subject suffering from a disease or condition mediated by c-kit and c-fms and a kit for modulating c-kit and c-fms.

EFFECT: novel compounds which can be useful in treating c-kit-mediated diseases or conditions and/or c-fms-mediated diseases or conditions are obtained and described.

21 cl, 44 ex

Polycyclic compound // 2451685

FIELD: medicine, pharmaceutics.

SUBSTANCE: described is a new polycyclic compound with general formula (I-1) and (1-3) or a pharmaceutically acceptable salt thereof where X1- -CR1 =CR2 - where R1 and R2 independently stand for hydrogen or C1-6 alkyl while Het stands for a radical of the following formulae: that may be substituted 1-3 times additionally described is a pharmaceutical composition containing such compound and intended for prevention or treatment of diseases caused by β-amyloid.

EFFECT: production of a pharmaceutical composition prevention or treatment of diseases caused by β-amyloid.

7 cl, 392 ex, 12 tbl

FIELD: chemistry.

SUBSTANCE: present invention relates to substituted imidazopyridine derivatives of general formula (I) or enantiomers, diastereomers and tautomers and pharmaceutically acceptable salts thereof, in which A denotes -NH-, -CH2-, -CH2-CH2- or a bond; X denotes phenyl, phenyl condensed with a saturated heterocyclic 5- or 6-member ring, where the heterocyclic ring can contain one or two heteroatoms selected from O and N, and where the heterocyclic ring can further be substituted with an oxo group, a 6-member saturated heterocyclyl containing O as a heteroatom, a 5-6-member heteroaryl containing 1 or 2 heteroatoms selected from N, O and S, and where each phenyl and heteroaryl is possibly substituted with 1 to 2 R14 and/or 1 substitute R4b and/or 1 substitute R5; R1 and R2 are independently selected from the following groups: C1-6-alkyl and C1-6-alkylene-C3-7-cycloalkyl, and where each alkyl is possibly substituted with a OH group, or R1 and R2 together with the nitrogen atom with which they are bonded form a 5-6-member ring which is possibly substituted with one substitute selected from C1-6-alkyl and O-C1-6-alkyl; R4b denotes C(O)NH2, C(O)OH, C(O)NH-C1-6-alkyl, C(O)N-(C1.6-alkyl)2, SO2-C1-6-alkyl, oxo group, and where the ring is at least partially saturated, NH2, NH-C1-6-alkyl, N-(C1-6-alkyl)2; R5 denotes a 6-member heteroaryl containing N as a heteroatom; R3 denotes -(CR8R9)n-T; R8 and R9 are independently selected from the following groups: H and C1-6-alkyl; n equals 1, 2, 3, 4, 5 or 6; T denotes or NR12R13; R10 denotes H, NH2, OH, C1-6-alkyl, possibly substituted with one OH, a halogen atom, NH(C1-6-alkyl) or N(C1-6-alkyl)2; q equals 1 or 2; Y denotes CH2, NR11 or O; R11 denotes H, or C1-6-alkyl; R12 and R13 are independently selected from the following groups: H, C1-6-alkyl, C1-6-alkynyl, (CH2)0-2-C3-7-cycloalkyl, and C1-6-alkylene-O- C1-6-alkyl, where C1-6-alkyl is possibly substituted with one halogen; R14 denotes a halogen atom, CN, C1-6-alkyl, possibly substituted with 1-3 substitutes selected from halogen atom, OH, O- C1-6-alkyl, O-C(O)C1-6-alkyl, O- C1-6-alkyl, possibly substituted with one substitute selected from OH, O- C1-6-alkyl, and O-C(O) C1-6-alkyl, or OH. The invention also relates to a pharmaceutical composition based on the compound of formula (I).

EFFECT: novel imidazopyridine derivatives are obtained, which can be used as melanocortin-4 receptor modulators.

17 cl, 8 tbl, 22 ex

New compounds // 2456273

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to compounds of formula: wherein B is specified in a group consisting of pyridine, pyridazine, pyrimidine and oxazole which can be optionally substituted by halogen, C1-7-alkyl or a C1-7-alkoxy group; L1 is specified in a group consisting of -NH-, -C(O)NH- and -NHC(O)-, A means C3-C12-cycloalkyl, C6-C12-aryl, a 4-7-member monocyclic heterocyclic group consisting of 1-3 heteroatoms optionally specified in O N and S, or a bicyclic heterocyclyl specified in a group consisting of benzimidazolyl, benzoxazolyl, benzothiazolyl, wherein cycloalkyl, aryl, mono- or bicyclic heterocyclyl can be optionally substituted by one or more substitutes optionally specified in a group consisting of a cyano group, halogen, an oxo group, C1-7-alkyl, C1-7-halogenalkyl, a C1-7-alkoxy group, C1-7-halogenalkoxy group, an amino group, a di-C1-7-alkylamino group, a C1-7-alkylthio group and C3-8-cycloalkyl, 1-2- means a bivalent residue specified in a group consisting of: - a bivalent alkyl group consisting of 1 to 4 carbon atoms, a bivalent alkenyl group consisting of 2 to 3 carbon atoms, - -C(O)-, - -C(O)-[R4]c-R5- wherein c is equal to 0, and R5 is specified in a group consisting of a bivalent C1-C4-alkyl group optionally substituted by another C1-4-alkyl, a C4-C8-cycloalkyl group, a phenyl group and a 5- or 6-member heterocyclyl group consisting of N heteroatoms, - -C(O)-NH-, - -(CH2)1-3-C(O)-NH-(CH2)1-3-, - -C(O)-NH-R4- wherein R4 is specified in a group consisting of a bivalent C1-C7-alkyl group optionally substituted by another C1-4-alkyl, a cyclohexyl group and a cyclopentyl group, and E is specified in a group consisting of: - COOH, - a ester group of carboxylic acid, or to its pharmaceutically acceptable salts. What is also described is a pharmaceutical composition exhibiting DGAT1 modulatory activity, on the basis of the presented compounds, and also a method of treating pathological conditions or disorders associated with DGAT1 activity.

EFFECT: there are prepared and described new compounds applicable for treating or preventing the pathological conditions or disorders associated with DGAT1 activity.

22 cl, 8 ex

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