3-pyridine carboxamide and 2-pyrazine carboxamide derivatives as hdl-cholesterol raising agents

FIELD: chemistry.

SUBSTANCE: invention relates to a compound of formula I:

, where A denotes CH or N; R1 is selected from a group consisting of: cycloalkyl which is unsubstituted or substituted with hydroxy, lower hydroxyalkyl or lower alkoxy, 1-hydroxy-2-indanyl, lower hydroxyalkyl, lower hydroxy haloalkyl, lower hydroxy alkoxyalkyl, CH2-CR9R10-cycloalkyl and -CR11R12- COOR13; R9 denotes hydrogen or lower alkyl; R10 denotes hydrogen, hydroxy or lower alkoxy; R11 and R12 independently denote hydrogen or lower alkyl; R13 denotes lower alkyl; R2 denotes hydrogen; or R1 and R2 together with the nitrogen atom with which they are bonded form a morpholinyl ring; R15 is selected from a group consisting of lower alkoxyalkyl, cycloalkyl and furanyl, substituted with halogen; R17 is selected from a group consisting of hydrogen, lower alkyl and lower haloalkyl; R4 and R8 independently denote hydrogen or halogen; R5 and R7 are independently selected from a group consisting of hydrogen, lower alkyl, lower alkoxy, halogen, lower haloalkyl, lower haloalkoxy and cyano; R6 is selected from a group consisting of hydrogen, lower alkoxy, halogen, lower haloalkyl, lower haloalkoxy and cyano; and pharmaceutically acceptable salts thereof. The invention also relates to use of said compounds to produce medicinal agents for treating and/or preventing diseases which can be cured by HDL-cholesterol raising agents and to a pharmaceutical composition based on said compounds.

EFFECT: novel compounds which can be useful in treating diseases which can be treated with HDL-cholesterol raising agents are obtained and described.

36 cl, 164 ex

 

The text descriptions are given in facsimile form.

1. The use of compounds of General formula:

where a represents CH or N;
R1selected from the group consisting of: cycloalkyl, which is unsubstituted or substituted by hydroxy, lower hydroxyalkyl or lower alkoxy, 1-hydroxy-2-indanyl, lower hydroxyalkyl, lower hydroxyalkenals, lower hydroxyalkoxy, -CH2-CR9R10-cycloalkyl and-CR11R12-COOR13;
R9represents hydrogen or lower alkyl;
R10represents hydrogen, hydroxy or lower alkoxy;
R11and R12independently from each other represent hydrogen or lower alkyl;
R13represents lower alkyl;
R2represents hydrogen; or
R1and R2together with the nitrogen atom to which they are attached, form morpholinyl ring;
G represents a group selected from the group consisting of-X-R3, -C≡C-R15and-CH2-CH2-R16;
X represents O or NR14;
R14selected from the group consisting of hydrogen, lower alkyl and lower hydroxyalkyl;
R3selected from the group consisting of lower alkyl, cycloalkyl, lower cycloalkenyl, lower hydroxyalkyl, lower alkoxyalkyl, lower halogenoalkane, lower carbamoylethyl, issaga of alkylcarboxylic, lower phenylalkyl, lower geterotsiklicheskikh where heterocyclyl group is unsubstituted or substituted by oxo, lower heteroallyl, where the heteroaryl group is unsubstituted or mono - or tizamidine lower alkyl, and phenyl, which is unsubstituted or mono - or Disaese halogen; or
R3and R14together with the nitrogen atom to which they are attached, form a 4-, 5-, 6 - or 7-membered heterocyclic ring, optionally containing another heteroatom selected from nitrogen, oxygen or sulphur, with the specified heterocyclic ring is unsubstituted or substituted by one or two groups independently selected from hydroxy, lower alkoxy and halogen;
R15selected from the group consisting of lower alkoxyalkyl, cycloalkyl and furanyl, substituted with halogen;
R16selected from the group consisting of cycloalkyl, which is unsubstituted or substituted by hydroxy or lower alkoxy, heteroaryl selected from pyridyl or imidazolyl, which is unsubstituted or substituted by lower alkyl or halogen, and lower alkylaminocarbonyl;
R17selected from the group consisting of hydrogen, lower alkyl and lower halogenoalkane;
R4and R8independently from each other represent hydrogen or halogen;
R5and R7independent is from each other selected from the group consisting of hydrogen, lower alkyl, lower alkoxy, halogen, lower halogenoalkane, lower halogenoalkane and cyano;
R6selected from the group consisting of hydrogen, lower alkoxy, halogen, lower halogenoalkane, lower halogenoalkane and cyano;
and their pharmaceutically acceptable salts,
for the manufacture of medicines for the treatment and/or prophylaxis of diseases which can be cured by agents that increase HDL-cholesterol.

2. The use according to claim 1, where the compounds of formula I have the formula:

where a represents CH or N;
R1selected from the group consisting of cycloalkyl, which is unsubstituted or substituted by hydroxy, lower hydroxyalkyl or lower alkoxy, 1-hydroxy-2-indanyl, lower hydroxyalkyl, lower hydroxyalkenals, lower hydroxyalkoxy, -CH2-CR9R10-cycloalkyl and-CR11R12-COOR13;
R9represents hydrogen or lower alkyl;
R10represents hydrogen, hydroxy or lower alkoxy;
R11and R12independently from each other represent hydrogen or lower alkyl;
R13represents lower alkyl;
R2represents hydrogen;
or R1and R2together with the nitrogen atom to which they are attached, clicks the form morpholinyl ring;
X represents O or NR14;
R14selected from the group consisting of hydrogen, lower alkyl and lower hydroxyalkyl;
R3selected from the group consisting of lower alkyl, cycloalkyl, lower cycloalkenyl, lower hydroxyalkyl, lower alkoxyalkyl, lower halogenoalkane, lower carbamoylethyl, lower alkylcarboxylic, lower phenylalkyl, lower geterotsiklicheskikh where heterocyclyl group is unsubstituted or substituted by oxo, lower heteroallyl, where the heteroaryl group is unsubstituted or mono - or tizamidine lower alkyl, and phenyl, which is unsubstituted or mono - or Disaese halogen;
or R3and R14together with the nitrogen atom to which they are attached, form a 4-, 5-, 6 - or 7-membered heterocyclic ring, optionally containing another heteroatom selected from nitrogen, oxygen or sulfur, with the specified heterocyclic ring is unsubstituted or substituted by one or two groups independently selected from hydroxy, lower alkoxy and halogen;
R4and R8independently from each other represent hydrogen or halogen;
R5and R7independently from each other selected from the group consisting of hydrogen, lower alkyl, lower alkoxy, halogen, lower halogenoalkane, Nisse what about halogenoalkane and cyano;
R6selected from the group consisting of hydrogen, lower alkoxy, halogen, lower halogenoalkane, lower halogenoalkane and cyano;
R17selected from the group consisting of hydrogen, lower alkyl and lower halogenoalkane;
and their pharmaceutically acceptable salts,
for the manufacture of medicines for the treatment and/or prophylaxis of diseases which can be cured by agents that increase HDL-cholesterol.

3. The use according to claim 1, where the compounds of formula I have the formula:
,
where A, R1-R8, R15and R17are as defined in claim 1, and their pharmaceutically acceptable salts,
for the manufacture of medicines for the treatment and/or prophylaxis of diseases which can be cured by agents that increase HDL-cholesterol.

4. The use according to claim 1, where the compounds of formula I have the formula:
,
where A, R1-R8, R16and R17are as defined in claim 1, and their pharmaceutically acceptable salts,
for the manufacture of medicines for the treatment and/or prophylaxis of diseases which can be cured by agents that increase HDL-cholesterol.

5. The use of compounds of the formula I according to claim 1, where a represents CH.

6. The use of compounds of the formula I according to claim 1, DG is And represents N.

7. The use according to claim 1, where the compounds of formula I have the formula:

where R1selected from the group consisting of cycloalkyl, which is unsubstituted or substituted by hydroxy or lower alkoxy, lower hydroxyalkyl, lower hydroxyalkenals, -CH2-CR9R10-cycloalkyl and-CR11R12-COOR13;
R9represents hydrogen or lower alkyl;
R10represents hydrogen, hydroxy or lower alkoxy;
R11and R12independently from each other represent hydrogen or lower alkyl;
R13represents lower alkyl;
R2represents hydrogen;
X represents O or NR14;
R14represents hydrogen or lower alkyl;
R3selected from the group consisting of lower alkyl, cycloalkyl, lower cycloalkenyl, lower alkoxyalkyl, lower halogenoalkane, lower carbamoylethyl, lower phenylalkyl, lower geterotsiklicheskikh, lower heteroallyl, where the heteroaryl group is unsubstituted or mono - or tizamidine halogen, and phenyl, which is unsubstituted or mono - or Disaese halogen; or
R3and R14together with the nitrogen atom to which they are attached, form a 5-, 6 - or 7-membered heterocyclic ring;
R4and R8/sup> independently from each other represent hydrogen or halogen;
R5and R7independently from each other selected from the group consisting of hydrogen, halogen, lower halogenoalkane, lower halogenoalkane and cyano;
R6selected from the group consisting of hydrogen, halogen, lower halogenoalkane, lower halogenoalkane and cyano;
and their pharmaceutically acceptable salts,
for the manufacture of medicinal products for the treatment and/or prophylaxis of diseases which can be cured by agents that increase HDL-cholesterol.

8. The use of compounds of the formula I according to claim 1, where X represents O.

9. The use of compounds of the formula I according to claim 1, where R1is cycloalkyl, substituted hydroxy.

10. The use of compounds of the formula I according to claim 1, where R1represents a
-CH2CR9R10-cycloalkyl, and where R9represents hydrogen, and R10represents hydroxy.

11. The use of compounds of the formula I according to claim 1, where R3selected from the group consisting of lower cycloalkenyl, lower alkoxyalkyl and lower halogenoalkane.

12. The use of compounds of the formula I according to claim 1, where R6represents halogen or lower halogenated, and R4, R5, R7and R8represent hydrogen.

13. The use of compounds of formula I by A1, where
R1is cycloalkyl, which is substituted by hydroxy, or-CH2-CR9R10-cycloalkyl;
R9represents hydrogen or lower alkyl;
R10represents hydrogen, hydroxy or lower alkoxy;
R2represents hydrogen;
X represents O;
R3selected from the group consisting of lower cycloalkenyl, lower alkoxyalkyl and lower halogenoalkane;
R4, R5, R7and R8represent hydrogen;
R6is a halogen;
and their pharmaceutically acceptable salts.

14. The use of compounds of the formula I according to claim 7, selected from the group consisting of the following compounds:
5-(4-chlorophenyl)-6-cyclopropylmethoxy-N-((1R,2R)-2-hydroxycyclohexyl)nicotinamide,
5-(4-chlorophenyl)-N-((1R,2R)-2-hydroxycyclohexyl)-6-(2-methoxyethoxy)nicotinamide,
N-((R)-2-cyclopropyl-2-hydroxypropyl)-6-cyclopropylmethoxy-5-(4-forfinal)nicotinamide,
5-(4-chlorophenyl)-N-((1R,2R)-2-hydroxycyclohexyl)-6-(2,2,2-triptoreline)nicotinamide,
6 cyclopropylmethoxy-5-(4-forfinal)-N-((1R,2R)-2-hydroxycyclohexyl)nicotinamide
and their pharmaceutically acceptable salts.

15. The use of compounds of the formula I according to claim 1, selected from the group consisting of the following compounds:
5-(4-chlorophenyl)-6-cyclopropylmethoxy-N-((1R,2R)-2-hydroxycyclohexyl)nicotinamide,
5-(4-harfe who yl)-N-((1R,2R)-2-hydroxycyclohexyl)-6-(2-methoxyethoxy)nicotinamide,
6 cyclopropylmethoxy-5-(4-forfinal)-N-((1R,2R)-2-hydroxycyclohexyl)nicotinamide,
5-(4-chlorophenyl)-N-((1R,2R)-2-hydroxycyclohexyl)-6-(2,2,2-triptoreline)nicotinamide,
N-((R)-2-cyclopropyl-2-hydroxypropyl)-6-cyclopropylmethoxy-5-(4-forfinal)nicotinamide,
6 butoxy-5-(4-chlorophenyl)-N-((1R,2R)-2-hydroxycyclohexyl)nicotinamide,
5-(4-chlorophenyl)-N-(2-cyclopropyl-2-hydroxypropyl)-6-cyclopropylacetylene,
6 cyclopentyloxy-5-(2-fluoro-5-triptoreline)-N-((1R,2R)-2-hydroxycyclohexyl)nicotinamide,
((1R,2R)-2-hydroxycyclohexyl)amide 6-(2-chlorophenyl)-5-pyrrolidin-1-Alperin-2-carboxylic acid,
((1R,2R)-2-hydroxycyclohexyl)amide 6-(2-chlorophenyl)-5-cyclopentenopyridine-2-carboxylic acid,
5-(4-chlorophenyl)-6-cyclopentyloxy-N-((1R,2R)-2-hydroxycyclohexyl)nicotinamide,
5-(2-chloro-5-triptoreline)-N-(2-cyclopropyl-2-hydroxypropyl)-6-cyclopropylacetylene,
(1-hydroxyine-2-yl)amide 6-(4-chlorophenyl)-5-piperidine-1-Alperin-2-carboxylic acid,
(2-cyclopropyl-2-hydroxypropyl)amide 6-(3,4-dichlorophenyl)-5-pyrrolidin-1-Alperin-2-carboxylic acid,
5-(4-chlorophenyl)-N-((R)-1-hydroxymethylene)-6-(2-methoxyethoxy)nicotinamide,
6 cyclopropylmethoxy-5-(4-forfinal)-N-((TRANS)-2-hydroxycyclohexyl)nicotinamide,
6 cyclopropylmethoxy-5-(3,4-dichlorophenyl)-N-((TRANS)-2-hydroxycyclohexyl)nicotinamide,
((R)-1-hydroxymethyl-3-methylbutyl)AMI is 6-(4-chlorophenyl)-5-cyclopropylmethoxy-2-carboxylic acid,
(2-cyclopropyl-2-hydroxypropyl)amide 6-(4-forfinal)-5-(3-methoxypropane)pyrazin-2-carboxylic acid,
(2-cyclopropyl-2-hydroxypropyl)amide 5-cyclopropylmethoxy-6-(4-forfinal)pyrazin-2-carboxylic acid,
6-((R)-sec-butoxy)-5-(4-chlorophenyl)-N-((1R,2R)-2-hydroxycyclohexyl)nicotinamide,
5-(4-chlorophenyl)-N-((1R,2R)-2-hydroxycyclohexyl)-6-[(2-methoxyethyl)methylamino]nicotinamide,
5-(4-chlorophenyl)-N-((1R,2R)-2-hydroxycyclohexyl)-6-(2-methoxy-1-methylethoxy)nicotinamide,
5-(4-chlorophenyl)-N-((1R,2R)-2-hydroxycyclohexyl)-6-(1-methoxymethylethoxy)nicotinamide,
(2-cyclopropyl-2-hydroxypropyl)amide 6-(4-forfinal)-5-((R)-2-methoxypropane)pyrazin-2-carboxylic acid,
((R)-2-cyclopropyl-2-hydroxypropyl)amide 6-(4-chlorophenyl)-5-[(R)-1-(tetrahydrofuran-2-yl)methoxy]pyrazin-2-carboxylic acid,
5-(4-chlorophenyl)-N-((1R,2R)-2-hydroxycyclohexyl)-6-((S)-2-methoxypropane)nicotinamide,
6-Deut-butoxy-5-(4-chlorophenyl)-N-((1R,2R)-2-hydroxycyclohexyl)nicotinamide,
((R)-2-cyclopropyl-2-hydroxypropyl)amide 6-(4-chlorophenyl)-5-(3-methylbutylamine)pyrazin-2-carboxylic acid,
((R)-2-cyclopropyl-2-hydroxypropyl)amide 6-(4-chlorophenyl)-5-(cyclopropylamino)pyrazin-2-carboxylic acid,
5-(4-chlorophenyl)-N-(2-cyclopropyl-2-hydroxypropyl)-6-(2,2,2-triptoreline)nicotinamide,
((R)-2-cyclopropyl-2-hydroxypropyl)amide 5,6-bis-(4-chlorophenyl)pyrazin-2-carboxylic acid,
5-(4-chlorophenyl)-6-(a cycle is propylethylenediamine)-N-((1R,2R)-2-hydroxycyclohexyl)nicotinamide,
6-(cyclopropanemethylamine)-5-(4-forfinal)-N-((1R,2R)-2-hydroxycyclohexyl)nicotinamide,
N-(2-cyclopropyl-2-hydroxypropyl)-6-(cyclopropanemethylamine)-5-(4-forfinal)nicotinamide,
N-((S)-2-cyclopropyl-2-hydroxypropyl)-6-cyclopropylmethoxy-5-(4-triptoreline)nicotinamide,
((R)-2-cyclopropyl-2-hydroxypropyl)amide 5-butoxy-6-(4-chlorophenyl)pyrazin-2-carboxylic acid,
5-(4-chlorophenyl)-N-((1R,2R)-2-hydroxycyclohexyl)-6-(methylpropylamine)nicotinamide,
5-(4-chlorophenyl)-N-(2-cyclopropyl-2-hydroxypropyl)-6-(methylpropylamine)nicotinamide,
((R)-2-cyclopropyl-2-hydroxypropyl)amide 5-cyclopropylmethoxy-6-(4-triptoreline)pyrazin-2-carboxylic acid,
N-((S)-2-cyclopropyl-2-hydroxypropyl)-6-(2-methoxyethoxy)-5-(4-triptoreline)nicotinamide,
5-(4-forfinal)-N-((1R,2R)-2-hydroxycyclohexyl)-6-(methylpropylamine)nicotinamide,
N-((S)-2-cyclopropyl-2-hydroxypropyl)-6-cyclopropylmethoxy-5-(4-trifloromethyl)nicotinamide,
5-(4-chlorophenyl)-N-((S)-2-cyclopropyl-2-hydroxypropyl)-6-(pyridine-4-ylethoxy)nicotinamide,
((S)-2-cyclopropyl-2-hydroxypropyl)amide 6-(4-forfinal)-5-(2,2,2-triptoreline)pyrazin-2-carboxylic acid,
((1R,2R)-2-hydroxycyclohexyl)amide 6-(4-forfinal)-5-(2,2,2-triptoreline)pyrazin-2-carboxylic acid,
((1R,2R)-2-hydroxycyclohexyl)amide 6-(4-forfinal)-5-(2-methoxyethoxy)pyrazin-2-carboxylic acid,
((1R,2R)-2-hidroxizina exil)amide 5-cyclopropylmethoxy-6-(4-forfinal)pyrazin-2-carboxylic acid,
5-(4-chlorophenyl)-N-((R)-2-cyclopropyl-2-hydroxypropyl)-6-cyclopropylacetylene,
5-(4-chlorophenyl)-N-((S)-2-cyclopropyl-2-hydroxypropyl)-6-cyclopropylacetylene,
5-(4-chlorophenyl)-N-((R)-2-cyclopropyl-2-hydroxypropyl)-6-(3-methylisoxazol-5-ylethoxy)nicotinamide,
((1R,2R)-2-hydroxycyclohexyl)amide 5-cyclopropylmethoxy-6-(4-trifloromethyl)pyrazin-2-karbonovoi acid,
((1R,2R)-2-hydroxycyclohexyl)amide 5-(cyclopropanemethylamine)-6-(4-trifloromethyl)pyrazin-2-carboxylic acid,
((R)-2-cyclopropyl-2-hydroxypropyl)amide 5-cyclopropylmethoxy-6-(4-trifloromethyl)pyrazin-2-carboxylic acid,
5-(4-chlorophenyl)-6-cyclopropylmethoxy-N-((1R,2R)-2-hydroxycyclohexyl)-2-nicotine amide,
N-((R)-2-cyclopropyl-2-hydroxypropyl)-5-(4-forfinal)-6-(pyridine-2-ylethoxy)nicotinamide,
((R)-2-cyclopropyl-2-hydroxypropyl)amide 6-(4-chlorophenyl)-5-thiomorpholine-4-Alperin-2-carboxylic acid,
6 cyclopropylmethoxy-N-(3,3,3-Cryptor-2-hydroxy-2-methylpropyl)-5-(4-triptoreline)nicotinamide,
5-(4-chlorophenyl)-N-((1R,2R)-2-hydroxycyclohexyl)-6-(pyridine-2-ylethoxy)nicotinamide,
5-(4-cyanophenyl)-6-cyclopropylmethoxy-N-((1R,2R)-2-hydroxycyclohexyl)nicotinamide,
6 cyclopropylmethoxy-5-(4-forfinal)-N-((R)-3,3,3-Cryptor-2-hydroxy-2-methylpropyl " PP,
5-(4-chloro-3-were)-N-((R)-1-hydroxymethyl-3-methylbutyl)-6-pyrrolidin-1-lincocine the ID,
N-((R)-1-hydroxymethyl-3-methylbutyl)-5-(3-methoxyphenyl)-6-pyrrolidin-1-iniatiated,
N-((R)-1-hydroxymethyl-3-methylbutyl)-6-pyrrolidin-1-yl-5-(4-trifloromethyl)nicotinamide,
5-(4-chlorophenyl)-N-((1R,2R)-2-hydroxycyclohexyl)-6-(2-pyridin-2-retil)nicotinamide,
5-(4-chlorophenyl)-6-[2-(5-herperidin-2-yl)ethyl]-N-((1R,2R)-2-hydroxycyclohexyl)nicotinamide,
6-(4-butylcarbamoyl)-5-(4-chlorophenyl)-N-((1R,2R)-2-hydroxycyclohexyl)nicotinamide,
5-[4-(2-butylcarbamoyl)phenyl]-6-cyclopropylmethoxy-N-((1R,2R)-2-hydroxycyclohexyl)nicotinamide,
5-(2-forfinal)-N-((R)-1-hydroxymethyl-3-methylbutyl)-6-pyrrolidin-1-iniatiated,
5-(4-forfinal)-N-((R)-1-hydroxymethyl-3-methylbutyl)-6-pyrrolidin-1-iniatiated,
5-(3-chlorophenyl)-N-((R)-1-hydroxymethyl-3-methylbutyl)-6-pyrrolidin-1-iniatiated,
5-(4-chlorophenyl)-N-((R)-1-hydroxymethyl-3-methylbutyl)-6-pyrrolidin-1-iniatiated,
5-(3,4-dichlorophenyl)-N-((R)-1-hydroxymethyl-3-methylbutyl)-6-pyrrolidin-1-iniatiated,
((S)-1-hydroxymethyl-3-methylbutyl)amide 3'-(3-chlorophenyl)-3,4,5,6-tetrahydro-2H-[1,2']bipyridinyl-5'-carboxylic acid,
R3selected from the group consisting of lower cycloalkenyl, lower alkoxyalkyl and lower halogenoalkane;
R4, R5, R7and R8represent hydrogen;
R6is a halogen;
and their pharmaceutically acceptable salts.

16. The use of compounds is ormula I according to claim 1 for the treatment and/or prevention of cardiovascular disorders.

17. The use of compounds of the formula I according to claim 1 for the treatment and/or prevention of dyslipidemia.

18. Pharmaceutical compositions for the treatment and/or prophylaxis of diseases which can be treated with agents that increase HDL-cholesterol, comprising one or more compounds of the formula:

where a represents CH or N;
R1selected from the group consisting of: cycloalkyl, which is unsubstituted or substituted by hydroxy, lower hydroxyalkyl or lower alkoxy, 1-hydroxy-2-indanyl, lower hydroxyalkyl, lower hydroxyalkenals, lower hydroxyalkoxy, -CH2-CR9R10-cycloalkyl and-CR11R12-COOR13;
R9represents hydrogen or lower alkyl;
R10represents hydrogen, hydroxy or lower alkoxy;
R11and R12independently from each other represent hydrogen or lower alkyl;
R13represents lower alkyl;
R2represents hydrogen; or
R1and R2together with the nitrogen atom to which they are attached, form morpholinyl ring;
G represents a group selected from the group consisting of-X-R3, -C≡C-R15and-CH2-CH2-R16;
X represents O or NR14;
R14selected from the group sotoyama is hydrogen, lower alkyl and lower hydroxyalkyl;
R3selected from the group consisting of lower alkyl, cycloalkyl, lower cycloalkenyl, lower hydroxyalkyl, lower alkoxyalkyl, lower halogenoalkane, lower carbamoylethyl, lower alkylcarboxylic, lower phenylalkyl, lower geterotsiklicheskikh where heterocyclyl group is unsubstituted or substituted by oxo, lower heteroallyl, where the heteroaryl group is nezamescennych or mono - or tizamidine lower alkyl, and phenyl, which is unsubstituted or mono - or Disaese halogen;
or R3and R14together with the nitrogen atom to which they are attached, form a 4-,
5-, 6 - or 7-membered heterocyclic ring, optionally containing another heteroatom selected from nitrogen, oxygen or sulphur, with the specified heterocyclic ring is unsubstituted or substituted by one or two groups independently selected from hydroxy, lower alkoxy and halogen;
R15selected from the group consisting of lower alkoxyalkyl, cycloalkyl and furanyl, substituted with halogen;
R16selected from the group consisting of cycloalkyl, which is unsubstituted or substituted by hydroxy or lower alkoxy, heteroaryl selected from pyridyl or imidazolyl, which is unsubstituted or samewe is lower alkyl or halogen, and lower alkylaminocarbonyl;
R17selected from the group consisting of hydrogen, lower alkyl and lower halogenoalkane;
R4and R8independently from each other represent hydrogen or halogen;
R5and R7independently from each other selected from the group consisting of hydrogen, lower alkyl, lower alkoxy, halogen, lower halogenoalkane, lower halogenoalkane and cyano;
R6selected from the group consisting of hydrogen, lower alkoxy, halogen, lower halogenoalkane, lower halogenoalkane and cyano;
and their pharmaceutically acceptable salts.

19. Pharmaceutical compositions for the treatment and/or prophylaxis of diseases which can be treated with agents that increase HDL-cholesterol by p, where the compounds of formula I have the formula:

where a represents CH or N;
R1selected from the group consisting of cycloalkyl, which is unsubstituted or substituted by hydroxy, lower hydroxyalkyl or lower alkoxy, 1-hydroxy-2-indanyl, lower hydroxyalkyl, lower hydroxyalkenals, lower hydroxyalkoxy, -CH2-CR9R10-cycloalkyl and-CR11R12-COOR13;
R9represents hydrogen or lower alkyl;
R10represents hydrogen, hydroxy or lower alkoxy;
R1 and R12independently from each other represent hydrogen or lower alkyl;
R13represents lower alkyl;
R2represents hydrogen;
or R1and R2together with the nitrogen atom to which they are attached, form morpholinyl ring;
X represents O or NR14;
R14selected from the group consisting of hydrogen, lower alkyl and lower hydroxyalkyl;
R3selected from the group consisting of lower alkyl, cycloalkyl, lower cycloalkenyl, lower hydroxyalkyl, lower alkoxyalkyl, lower halogenoalkane, lower carbamoylethyl, lower alkylcarboxylic, lower phenylalkyl, lower geterotsiklicheskikh where heterocyclyl group is unsubstituted or substituted by oxo, lower heteroallyl, where the heteroaryl group is unsubstituted or mono - or tizamidine lower alkyl, and phenyl, which is unsubstituted or mono - or Disaese halogen; or
R3and R14together with the nitrogen atom to which they are attached, form a 4-, 5-, 6 - or 7-membered heterocyclic ring, optionally containing another heteroatom selected from nitrogen, oxygen or sulfur, with the specified heterocyclic ring is unsubstituted or substituted by one or two groups independently selected from hydroxy, who schego alkoxy and halogen;
R4and R8independently from each other represent hydrogen or halogen;
R5and R7independently from each other selected from the group consisting of hydrogen, lower alkyl, lower alkoxy, halogen, lower halogenoalkane, lower halogenoalkane and cyano;
R6selected from the group consisting of hydrogen, lower alkoxy, halogen, lower halogenoalkane, lower halogenoalkane and cyano;
R17selected from the group consisting of hydrogen, lower alkyl and lower halogenoalkane;
and their pharmaceutically acceptable salts.

20. Pharmaceutical compositions for the treatment and/or prophylaxis of diseases which can be treated with agents that increase HDL-cholesterol by p, where the compounds of formula I have the formula:

where A, R1-R8, R15and R17are as defined in p, and their pharmaceutically acceptable salts.

21. Pharmaceutical compositions for the treatment and/or prophylaxis of diseases which can be treated with agents that increase HDL-cholesterol by p, where the compounds of formula I have the formula:

where A, R1-R8, R16and R17are as defined in p, and their pharmaceutically acceptable salts.

22. Pharmaceutical compositions for p containing connection is of formula I, where a represents CH.

23. Pharmaceutical compositions for p containing the compounds of formula I, where a represents N.

24. Pharmaceutical compositions for the treatment and/or prophylaxis of diseases which can be treated with agents that increase HDL-cholesterol by p comprising one or more compounds of formula I having the formula:

where R1selected from the group consisting of cycloalkyl, which is unsubstituted or substituted by hydroxy or lower alkoxy, lower hydroxyalkyl, lower hydroxyalkenals, -CH2-CR9R10-cycloalkyl and-CR11R12-COOR13;
R9represents hydrogen or lower alkyl;
R10represents hydrogen, hydroxy or lower alkoxy;
R11and R12independently from each other represent hydrogen or lower alkyl;
R13represents lower alkyl;
R2represents hydrogen;
X represents O or NR14;
R14represents hydrogen or lower alkyl;
R3selected from the group consisting of lower alkyl, cycloalkyl, lower cycloalkenyl, lower alkoxyalkyl, lower halogenoalkane, lower carbamoylethyl, lower phenylalkyl, lower geterotsiklicheskikh, lower heteroallyl, where het is rohilla group is unsubstituted or mono - or tizamidine lower alkyl, and phenyl, which is unsubstituted or mono - or Disaese halogen;
or R3and R14together with the nitrogen atom to which they are attached, form a 5-, 6 - or 7-membered heterocyclic ring;
R4and R8independently from each other represent hydrogen or halogen;
R5and R7independently from each other selected from the group consisting of hydrogen, halogen, lower halogenoalkane, lower halogenoalkane and cyano;
R6selected from the group consisting of hydrogen, halogen, lower halogenoalkane, lower halogenoalkane and cyano;
or their pharmaceutically acceptable salts,
and a pharmaceutically acceptable carrier and/or adjuvant.

25. Pharmaceutical compositions for p containing the compounds of formula I, where X represents O.

26. Pharmaceutical compositions for p containing the compounds of formula I, where R1is cycloalkyl, substituted hydroxy.

27. Pharmaceutical compositions for p containing the compounds of formula I, where R1represents-CH2-CR9R10-cycloalkyl, and where R9represents hydrogen and R10represents hydroxy.

28. Pharmaceutical compositions for p containing the compounds of formula I, where R3selected from the group consisting of lower cycloalkenyl, lower alkoxyalkyl and neither is our halogenoalkane.

29. Pharmaceutical compositions for p containing the compounds of formula I, where R6represents halogen or lower halogenated, and R4, R5, R7and R8represent hydrogen.

30. Pharmaceutical compositions for p containing the compounds of formula I,
where R1is cycloalkyl, which is substituted by hydroxy, or-CH2-CR9R10-cycloalkyl;
R9represents hydrogen or lower alkyl;
R10represents hydrogen, hydroxy or lower alkoxy;
R2represents hydrogen;
X represents O;
R3selected from the group consisting of lower cycloalkenyl, lower alkoxyalkyl and lower halogenoalkane;
R4, R5, R7and R8represent hydrogen;
R6is a halogen;
or their pharmaceutically acceptable salts.

31. The pharmaceutical composition of paragraph 24, containing compounds selected from the group consisting of the following compounds:
5-(4-chlorophenyl)-6-cyclopropylmethoxy-N-((1R,2R)-2-hydroxycyclohexyl)nicotinamide,
5-(4-chlorophenyl)-N-((1R,2R)-2-hydroxycyclohexyl)-6-(2-methoxyethoxy)nicotinamide,
N-((R)-2-cyclopropyl-2-hydroxypropyl)-6-cyclopropylmethoxy-5-(4-forfinal)nicotinamide,
5-(4-chlorophenyl)-N-((1R,2R)-2-hydroxycyclohexyl)-6-(2,2,2-triptoreline)nicotinamide,
6-cycle is propylketone-5-(4-forfinal)-N-((1R,2R)-2-hydroxycyclohexyl)nicotinamide
and their pharmaceutically acceptable salts.

32. Pharmaceutical compositions for p containing compounds selected from the group consisting of the following compounds:
5-(4-chlorophenyl)-6-cyclopropylmethoxy-N-((1R,2R)-2-hydroxycyclohexyl)nicotinamide,
5-(4-chlorophenyl)-N-((1R,2R)-2-hydroxycyclohexyl)-6-(2-methoxyethoxy)nicotinamide,
6 cyclopropylmethoxy-5-(4-forfinal)-N-((1R,2R)-2-hydroxycyclohexyl)nicotinamide,
5-(4-chlorophenyl)-N-((1R,2R)-2-hydroxycyclohexyl)-6-(2,2,2-triptoreline)nicotinamide,
N-((R)-2-cyclopropyl-2-hydroxypropyl)-6-cyclopropylmethoxy-5-(4-forfinal)nicotinamide,
6 butoxy-5-(4-chlorophenyl)-N-((1R,2R)-2-hydroxycyclohexyl)nicotinamide,
5-(4-chlorophenyl)-N-(2-cyclopropyl-2-hydroxypropyl)-6-cyclopropylacetylene,
6 cyclopentyloxy-5-(2-fluoro-5-triptoreline)-N-((1R,2R)-2-hydroxycyclohexyl)nicotinamide,
((1R,2R)-2-hydroxycyclohexyl)amide 6-(2-chlorophenyl)-5-pyrrolidin-1-Alperin-2-carboxylic acid,
((1R,2R)-2-hydroxycyclohexyl)amide 6-(2-chlorophenyl)-5-cyclopentenopyridine-2-carboxylic acid,
5-(4-chlorophenyl)-6-cyclopentyloxy-N-((1R,2R)-2-hydroxycyclohexyl)nicotinamide,
5-(2-chloro-5-triptoreline)-N-(2-cyclopropyl-2-hydroxypropyl)-6-cyclopropylacetylene,
(1-hydroxyine-2-yl)amide 6-(4-chlorophenyl)-5-piperidine-1-Alperin-2-carboxylic acid,
(2-cyclopropyl-2-hydroxypropyl)amide 6-(3,4-dichlorophenyl)-5-Pyrrhus is lidin-1-Alperin-2-carboxylic acid,
5-(4-chlorophenyl)-N-((R)-1-hydroxymethylene)-6-(2-methoxyethoxy)nicotinamide,
6 cyclopropylmethoxy-5-(4-forfinal)-N-((TRANS)-2-hydroxycyclohexyl)nicotinamide,
6 cyclopropylmethoxy-5-(3,4-dichlorophenyl)-N-((TRANS)-2-hydroxycyclohexyl)nicotinamide,
((R)-1-hydroxymethyl-3-methylbutyl)amide 6-(4-chlorophenyl)-5-cyclopropylmethoxy-2-carboxylic acid,
(2-cyclopropyl-2-hydroxypropyl)amide 6-(4-forfinal)-5-(3-methoxypropane)pyrazin-2-carboxylic acid,
(2-cyclopropyl-2-hydroxypropyl)amide 5-cyclopropylmethoxy-6-(4-forfinal)pyrazin-2-carboxylic acid,
6-((R)-sec-butoxy)-5-(4-chlorophenyl)-N-((1R,2R)-2-hydroxycyclohexyl)nicotinamide,
5-(4-chlorophenyl)-N-((1R,2R)-2-hydroxycyclohexyl)-6-[(2-methoxyethyl)methylamino]nicotinamide,
5-(4-chlorophenyl)-N-((1R,2R)-2-hydroxycyclohexyl)-6-(2-methoxy-1-methylethoxy)nicotinamide,
5-(4-chlorophenyl)-N-((1R,2R)-2-hydroxycyclohexyl)-6-(1-methoxymethylethoxy)nicotinamide,
(2-cyclopropyl-2-hydroxypropyl)amide 6-(4-forfinal)-5-((R)-2-methoxypropane)pyrazin-2-carboxylic acid,
((R)-2-cyclopropyl-2-hydroxypropyl)amide 6-(4-chlorophenyl)-5-[(R)-1-(tetrahydrofuran-2-yl)methoxy]pyrazin-2-carboxylic acid,
5-(4-chlorophenyl)-N-((1R,2R)-2-hydroxycyclohexyl)-6-((S)-2-methoxypropane)nicotinamide,
6-Deut-butoxy-5-(4-chlorophenyl)-N-((1R,2R)-2-hydroxycyclohexyl)nicotinamide,
((R)-2-cyclopropyl-2-hydroxypropyl)amide 6-(4-chlorophenyl)-5-(3-methyl is ethylamino)pyrazin-2-carboxylic acid,
((R)-2-cyclopropyl-2-hydroxypropyl)amide 6-(4-chlorophenyl)-5-(cyclopropylamino)pyrazin-2-carboxylic acid,
5-(4-chlorophenyl)-N-(2-cyclopropyl-2-hydroxypropyl)-6-(2,2,2-triptoreline)nicotinamide,
((R)-2-cyclopropyl-2-hydroxypropyl)amide 5,6-bis-(4-chlorophenyl)pyrazin-2-carboxylic acid,
5-(4-chlorophenyl)-6-(cyclopropanemethylamine)-N-((1R,2R)-2-hydroxycyclohexyl)nicotinamide,
6-(cyclopropanemethylamine)-5-(4-forfinal)-N-((1R,2R)-2-hydroxycyclohexyl)nicotinamide,
N-(2-cyclopropyl-2-hydroxypropyl)-6-(cyclopropanemethylamine)-5-(4-forfinal)nicotinamide,
N-((S)-2-cyclopropyl-2-hydroxypropyl)-6-cyclopropylmethoxy-5-(4-triptoreline)nicotinamide,
((R)-2-cyclopropyl-2-hydroxypropyl)amide 5-butoxy-6-(4-chlorophenyl)pyrazin-2-carboxylic acid,
5-(4-chlorophenyl)-N-((1R,2R)-2-hydroxycyclohexyl)-6-(methylpropylamine)nicotinamide,
5-(4-chlorophenyl)-N-(2-cyclopropyl-2-hydroxypropyl)-6-(methylpropylamine)nicotinamide,
((R)-2-cyclopropyl-2-hydroxypropyl)amide 5-cyclopropylmethoxy-6-(4-triptoreline)pyrazin-2-carboxylic acid,
N-((S)-2-cyclopropyl-2-hydroxypropyl)-6-(2-methoxyethoxy)-5-(4-triptoreline)nicotinamide,
5-(4-forfinal)-N-((1R,2R)-2-hydroxycyclohexyl)-6-(methylpropylamine)nicotinamide,
N-((S)-2-cyclopropyl-2-hydroxypropyl)-6-cyclopropylmethoxy-5-(4-trifloromethyl)nicotinamide,
5-(4-chlorophenyl)-N-((S)-2-cyclopropyl-2-Ki is oxypropyl)-6-(pyridine-4-ylethoxy)nicotinamide,
((S)-2-cyclopropyl-2-hydroxypropyl)amide 6-(4-forfinal)-5-(2,2,2-triptoreline)pyrazin-2-carboxylic acid,
((1R,2R)-2-hydroxycyclohexyl)amide 6-(4-forfinal)-5-(2,2,2-triptoreline)pyrazin-2-carboxylic acid,
((1R,2R)-2-hydroxycyclohexyl)amide 6-(4-forfinal)-5-(2-methoxyethoxy)pyrazin-2-carboxylic acid,
((1R,2R)-2-hydroxycyclohexyl)amide 5-cyclopropylmethoxy-6-(4-forfinal)pyrazin-2-carboxylic acid,
5-(4-chlorophenyl)-N-((R)-2-cyclopropyl-2-hydroxypropyl)-6-cyclopropylacetylene,
5-(4-chlorophenyl)-N-((S)-2-cyclopropyl-2-hydroxypropyl)-6-cyclopropylacetylene,
5-(4-chlorophenyl)-N-((R)-2-cyclopropyl-2-hydroxypropyl)-6-(3-methylisoxazol-5-ylethoxy)nicotinamide,
((1R,2R)-2-hydroxycyclohexyl)amide 5-cyclopropylmethoxy-6-(4-trifloromethyl)pyrazin-2-carboxylic acid,
((1R,2R)-2-hydroxycyclohexyl)amide 5-(cyclopropanemethylamine)-6-(4-trifloromethyl)pyrazin-2-carboxylic acid,
((R)-2-cyclopropyl-2-hydroxypropyl)amide 5-cyclopropylmethoxy-6-(4-trifloromethyl)pyrazin-2-carboxylic acid,
5-(4-chlorophenyl)-6-cyclopropylmethoxy-N-((1R,2R)-2-hydroxycyclohexyl)-2-nicotine amide,
N-((R)-2-cyclopropyl-2-hydroxypropyl)-5-(4-forfinal)-6-(pyridine-2-ylethoxy)nicotinamide,
((R)-2-cyclopropyl-2-hydroxypropyl)amide 6-(4-chlorophenyl)-5-thiomorpholine-4-Alperin-2-carboxylic acid,
6 cyclopropylmethoxy-N-(3,3,3-trip the PR-2-hydroxy-2-methylpropyl)-5-(4-triptoreline)nicotinamide,
5-(4-chlorophenyl)-N-((1R,2R)-2-hydroxycyclohexyl)-6-(pyridine-2-ylethoxy)nicotinamide,
5-(4-cyanophenyl)-6-cyclopropylmethoxy-N-((1R,2R)-2-hydroxycyclohexyl)nicotinamide,
6 cyclopropylmethoxy-5-(4-forfinal)-N-((R)-3,3,3-Cryptor-2-hydroxy-2-methylpropyl " PP,
5-(4-chloro-3-were)-N-((R)-1-hydroxymethyl-3-methylbutyl)-6-pyrrolidin-1-iniatiated,
N-((R)-1-hydroxymethyl-3-methylbutyl)-5-(3-methoxyphenyl)-6-pyrrolidin-1-iniatiated,
N-((R)-1-hydroxymethyl-3-methylbutyl)-6-pyrrolidin-1-yl-5-(4-trifloromethyl)nicotinamide,
5-(4-chlorophenyl)-N-((1R,2R)-2-hydroxycyclohexyl)-6-(2-pyridin-2-retil)nicotinamide,
5-(4-chlorophenyl)-6-[2-(5-herperidin-2-yl)ethyl]-N-((1R,2R)-2-hydroxycyclohexyl)nicotinamide,
6-(4-butylcarbamoyl)-5-(4-chlorophenyl)-N-((1R,2R)-2-hydroxycyclohexyl)nicotinamide,
5-[4-(2-butylcarbamoyl)phenyl]-6-cyclopropylmethoxy-N-((1R,2R)-2-hydroxycyclohexyl)nicotinamide,
5-(2-forfinal)-N-((R)-1-hydroxymethyl-3-methylbutyl)-6-pyrrolidin-1-iniatiated,
5-(4-forfinal)-N-((R)-1-hydroxymethyl-3-methylbutyl)-6-pyrrolidin-1-iniatiated,
5-(3-chlorophenyl)-N-((R)-hydroxymethyl-3-methylbutyl)-6-pyrrolidin-1-iniatiated,
5-(4-chlorophenyl)-N-((R)-1-hydroxymethyl-3-methylbutyl)-6-pyrrolidin-1-iniatiated,
5-(3,4-dichlorophenyl)-N-((R)-1-hydroxymethyl-3-methylbutyl)-6-pyrrolidin-1-iniatiated,
((S)-1-hydroxymethyl-3-methylbutyl)amide 3'-(3-chlorophenyl)-3,4,5,6-tetrahydro-2H-[,2']bipyridinyl-5'-carboxylic acid
and their pharmaceutically acceptable salts.

33. Pharmaceutical compositions for p for the treatment and/or prevention of cardiovascular disorders.

34. Pharmaceutical compositions for p for the treatment and/or prevention of dyslipidemia.

35. The compounds of formula I, selected from the group consisting of the following compounds:
6 cyclohexyloxy-5-(2-fluoro-5-triptoreline)-N-((1R,2R)-2-hydroxycyclohexyl)nicotinamide,
6 butoxy-N-(2-cyclopropyl-2-hydroxypropyl)-5-(2-fluoro-5-triptoreline)nicotinamide,
5-(4-chlorophenyl)-6-cyclohexyloxy-N-((1R,2R)-2-hydroxycyclohexyl)nicotinamide,
6 cyclopentyloxy-5-(2-fluoro-5-triptoreline)-N-((1R,2R)-2-hydroxycyclohexyl)nicotinamide,
6 cyclopentyloxy-N-(2-cyclopropyl-2-hydroxypropyl)-5-(2-fluoro-5-triptoreline)nicotinamide,
((1R,2R)-2-hydroxycyclohexyl)amide 6-(2-chlorophenyl)-5-pyrrolidin-1-Alperin-2-carboxylic acid,
((1R,2R)-2-hydroxycyclohexyl)amide 6-(2-chlorophenyl)-5-cyclopentenopyridine-2-carboxylic acid,
5-(4-chlorophenyl)-6-cyclopentyloxy-N-((1R,2R)-2-hydroxycyclohexyl)nicotinamide,
5-(2-chloro-5-triptoreline)-N-(2-cyclopropyl-2-hydroxypropyl)-6-cyclopropylacetylene,
5-(4-chlorophenyl)-N-((1R,2R)-2-hydroxycyclohexyl)-6-phenoxyimine,
(1-hydroxyine-2-yl)amide 6-(4-chlorophenyl)-5-piperidine-1-Alperin-2-carboxylic acid,
(2-cyclopropyl-2-hydroxypropyl)amide 6-(34-dichlorophenyl)-5-pyrrolidin-1-Alperin-2-carboxylic acid,
[5-(4-chlorophenyl)-6-(2-methoxyethoxy)pyridine-3-yl]morpholine-4-ylmethanone,
5-(4-chlorophenyl)-N-((R)-1-hydroxymethyl-3-methylbutyl)-6-(2-propionyloxy)nicotinamide,
5-(4-chlorophenyl)-N-((R)-1-hydroxymethylene)-6-(2-methoxyethoxy)nicotinamide,
5-(4-chlorophenyl)-N-((S)-1-hydroxymethyl-2,2-dimethylpropyl)-6-(2-methoxyethoxy)nicotinamide,
6 cyclopropylmethoxy-5-(3,4-dichlorophenyl)-N-((TRANS)-2-hydroxycyclohexyl)nicotinamide,
((R)-1-hydroxymethyl-3-methylbutyl)amide 6-(4-chlorophenyl)-5-cyclopropylmethoxy-2-carboxylic acid,
5-(4-chlorophenyl)-N-(2-hydroxy-3-methoxypropyl)-6-(2-methoxyethoxy)nicotinamide,
((1R,2R)-2-hydroxycyclohexyl)amide 5-(2-chlorophenoxy)-6-(4-chlorophenyl)pyrazin-2-carboxylic acid,
(2-cyclopropyl-2-hydroxypropyl)amide 6-(4-forfinal)-5-(3-methoxypropane)pyrazin-2-carboxylic acid,
6-((R)-sec-butoxy)-5-(4-chlorophenyl)-N-((1R,2R)-2-hydroxycyclohexyl)nicotinamide,
5-(4-chlorophenyl)-N-((1R,2R)-2-hydroxycyclohexyl)-6-isopropoxyaniline,
5-(4-chlorophenyl)-N-((1R,2R)-2-hydroxycyclohexyl)-6-(2-methoxy-1-methylethoxy)nicotinamide,
5-(4-chlorophenyl)-N-((1R,2R)-2-hydroxycyclohexyl)-6-(1-methoxymethylethoxy)nicotinamide,
(2-cyclopropyl-2-hydroxypropyl)amide 6-(4-forfinal)-5-((R)-2-methoxypropane)pyrazin-2-carboxylic acid,
5-(4-chlorophenyl)-N-((1R,2R)-2-hydroxycyclohexyl)-6-((S)-2-methoxypropane)nicotinamide,
6-Deut-butoxy-5-(4-chlorophenyl)-N-((1R,2R)-2-hydroc illogical)nicotinamide,
(2-cyclopropyl-2-hydroxypropyl)amide 5-cyclopropylmethoxy-6-(4-triptoreline)pyrazin-2-carboxylic acid,
((R)-2-cyclopropyl-2-hydroxypropyl)amide 6-(4-chlorophenyl)-5-(3-methylbutylamine)pyrazin-2-carboxylic acid,
((R)-2-cyclopropyl-2-hydroxypropyl)amide 6-(4-chlorophenyl)-5-cyclopropylamino-2-carboxylic acid,
((R)-2-cyclopropyl-2-hydroxypropyl)amide 6-(4-chlorophenyl)-5-(3-methoxyisatin-1-yl)pyrazin-2-carboxylic acid,
5-(4-chlorophenyl)-N-((1R,2R)-2-hydroxycyclohexyl)-6-[3-(2-oxopyrrolidin-1-yl)propoxy]nicotinamide,
5-(4-forfinal)-N-((1R,2R)-2-hydroxycyclohexyl)-6-(3-methoxypropane)nicotinamide,
((S)-2-cyclopropyl-2-hydroxypropyl)amide 6-(4-chlorophenyl)-5-[(5)-1-(tetrahydrofuran-2-yl)methoxy]pyrazin-2-carboxylic acid,
N-(2-cyclopropyl-2-hydroxypropyl)-6-(cyclopropanemethylamine)-5-(4-forfinal)nicotinamide,
5-(4-chlorophenyl)-N-(2-cyclopropyl-2-hydroxypropyl)-6-(methylpropylamine)nicotinamide,
((R)-2-cyclopropyl-2-hydroxypropyl)amide 5-cyclopropylmethoxy-6-(4-triptoreline)pyrazin-2-carboxylic acid,
N-((S)-2-cyclopropyl-2-hydroxypropyl)-6-(2-methoxyethoxy)-5-(4-triptoreline)nicotinamide,
5-(4-chlorophenyl)-N-(2-cyclopropyl-2-hydroxypropyl)-6-[(2-methoxyethyl)methylamino]nicotinamide,
(2-cyclopropyl-2-hydroxypropyl)amide 3'-(4-chlorophenyl)-3,4,5,6-tetrahydro-2H-[1,2']bipyridinyl-5'-carboxylic acid,
N-((S)-2-cyclopropyl-2-g is droxidopa)-6-cyclopropylmethoxy-5-(4-trifloromethyl)nicotinamide,
5-(4-chlorophenyl)-N-((S)-2-cyclopropyl-2-hydroxypropyl-6-(2-methyl-2H-[1,2,4]triazole-3-ylethoxy)nicotinamide,
5-(4-chlorophenyl)-N-((S)-2-cyclopropyl-2-hydroxypropyl)-6-(pyridine-4-ylethoxy)nicotinamide,
((S)-2-cyclopropyl-2-hydroxypropyl)amide 6-(4-forfinal)-5-(2,2,2-triptoreline)pyrazin-2-carboxylic acid,
((1R,2R)-2-hydroxycyclohexyl)amide 5-cyclopropylmethoxy-6-(4-forfinal)pyrazin-2-carboxylic acid,
5-(4-cyanophenyl)-N-((R)-2-cyclopropyl-2-hydroxypropyl)-6-cyclopropylacetylene,
5-(4-chlorophenyl)-N-((S)-2-cyclopropyl-2-hydroxypropyl)-6-cyclopropylacetylene,
6 cyclopropylmethoxy-5-(4-forfinal)-N-(1-hydroxymethylglutaryl)nicotinamide,
((R)-2-cyclopropyl-2-hydroxypropyl)amide 5-[bis-(2-hydroxyethyl)amino]-6-(4-chlorophenyl)pyrazin-2-carboxylic acid,
((R)-2-cyclopropyl-2-hydroxypropyl)amide 5-(5-bromofuran-2-ylethynyl)-6-(4-chlorophenyl)pyrazin-2-carboxylic acid,
5-(4-chlorophenyl)-N-((1R,2R)-2-hydroxycyclohexyl)-6-(3-methoxypropyl-1-inyl)nicotinamide,
5-(4-chlorophenyl)-6-cyclopropylamino-N-((1R,2R)-2-hydroxycyclohexyl)nicotinamide,
5-(4-chlorophenyl)-6-cyclopropylmethoxy-N-((1R,2R)-2-hydroxycyclohexyl)-2-nicotine amide,
((R)-2-cyclopropyl-2-hydroxypropyl)amide 5-(2-pyridin-3-retil)-6-(4-trifloromethyl)pyrazin-2-carboxylic acid,
5-(4-chlorophenyl)-N-((1R,2R)-2-hydroxycyclohexyl)-2-methyl-6-(2,2,2-triptoreline)nicotinamide,
((R)-2-Cyclops the sawdust-2-hydroxypropyl)amide 6-(4-chlorophenyl)-5-thiomorpholine-4-Alperin-2-carboxylic acid,
((R)-2-cyclopropyl-2-hydroxypropyl)amide 6-(4-chlorophenyl)-5-(4,4-deformability-1-yl)pyrazin-2-carboxylic acid,
((R)-2-cyclopropyl-2-hydroxypropyl)amide 6-(4-chlorophenyl)-5-(2-cyclopropylethyl)pyrazin-2-carboxylic acid,
((R)-2-cyclopropyl-2-hydroxypropyl)amide 5-(2-pyridin-2-retil)-6-(4-trifloromethyl)pyrazin-2-carboxylic acid,
((R)-2-cyclopropyl-2-hydroxypropyl)amide 6-(4-forfinal)-5-piperidine-1-Alperin-2-carboxylic acid,
5-(4-chlorophenyl)-N-((1R,2R)-2-hydroxycyclohexyl)-6-[2-(1-hydroxycyclopent)ethyl]nicotinamide,
6 cyclopropylmethoxy-5-(4-forfinal)-N-((R)-3,3,3-Cryptor-2-hydroxy-2-methylpropyl " PP,
5-(4-chlorophenyl)-6-cyclopropylmethoxy-N-((1R,2R)-2-hydroxycyclohexyl)-2-triftoratsetofenona,
N-((S)-1-hydroxymethyl-3-methylbutyl)-5-(3-methoxyphenyl)-6-pyrrolidin-1-iniatiated,
N-((S)-1-hydroxymethyl-3-methylbutyl)-5-(4-methoxyphenyl)-6-pyrrolidin-1-iniatiated,
5-(4-chloro-3-were)-N-((R)-1-hydroxymethyl-3-methylbutyl)-6-pyrrolidin-1-iniatiated,
N-((R)-1-hydroxymethyl-3-methylbutyl)-5-(3-methoxyphenyl)-6-pyrrolidin-1-iniatiated,
N-((R)-1-hydroxymethyl-3-methylbutyl)-5-(4-methoxyphenyl)-6-pyrrolidin-1-iniatiated,
N-((R)-1-hydroxymethyl-3-methylbutyl)-6-pyrrolidin-1-yl-5-(4-triptoreline)nicotinamide,
N-((R)-1-hydroxymethyl-3-methylbutyl)-6-pyrrolidin-1-yl-5-(4-trifloromethyl)nicotinamide,
5-(4-cyanophenyl)-N-((R)-1-hydro is simetal-3-methylbutyl)-6-pyrrolidin-1-iniatiated,
N-((1R,2R)-2-hydroxycyclohexyl)-6-[2-(3-methyl-3H-imidazol-4-yl)ethyl]-5-(4-triptoreline)nicotinamide,
methyl ester of (R)-2-{[6-(4-forfinal)-5-pyrrolidin-1-Alperin-2-carbonyl]amino}-3-methylbutanoic acid,
6-(4-butylcarbamoyl)-5-(4-chlorophenyl)-N-((1R,2R)-2-hydroxycyclohexyl)nicotinamide,
5-[4-(2-butylcarbamoyl)phenyl]-6-cyclopropylmethoxy-N-((1R,2R)-2-hydroxycyclohexyl)nicotinamide,
5-(2,4-dichlorophenyl)-N-(2-hydroxyethyl)-6-propoxyimino,
6 cyclopentyloxy-5-(2,4-dichlorophenyl)-N-(2-hydroxyethyl)nicotinamide,
5-(4-chlorophenyl)-N-((S)-1-hydroxymethyl-3-methylbutyl)-6-pyrrolidin-1-iniatiated,
5-(3,4-dichlorophenyl)-N-((S)-1-hydroxymethyl-3-methylbutyl)-6-pyrrolidin-1-iniatiated,
5-(4-chloro-3-were)-N-((S)-1-hydroxymethyl-3-methylbutyl)-6-pyrrolidin-1-iniatiated,
5-(2-forfinal)-N-((R)-1-hydroxymethyl-3-methylbutyl)-6-pyrrolidin-1-iniatiated,
5-(4-forfinal)-N-((R)-1-hydroxymethyl-3-methylbutyl)-6-pyrrolidin-1-iniatiated,
5-(3-chlorophenyl)-N-((R)-1-hydroxymethyl-3-methylbutyl)-6-pyrrolidin-1-iniatiated,
5-(4-chlorophenyl)-N-((R)-1-hydroxymethyl-3-methylbutyl)-6-pyrrolidin-1-iniatiated,
5-(3,4-dichlorophenyl)-N-((R)-1-hydroxymethyl-3-methylbutyl)-6-pyrrolidin-1-iniatiated,
((S)-1-hydroxymethyl-3-methylbutyl)amide 3'-(3-chlorophenyl)-3,4,5,6-tetrahydro-2H-[1,2']bipyridinyl-5'-carboxylic acid
and their pharmaceutically acceptable salts.

36. Soy is inane formula I, having the formula:

where a represents CH or N;
R1selected from the group consisting of: cycloalkyl, which is unsubstituted or substituted by hydroxy, lower hydroxyalkyl or lower alkoxy, 1-hydroxy-2-indanyl, lower hydroxyalkyl, lower hydroxyalkenals, lower hydroxyalkoxy, -CH2-CR9R10-cycloalkyl and-CR11R12-COOR13;
R9represents hydrogen or lower alkyl;
R10represents hydrogen, hydroxy or lower alkoxy;
R11and R12independently from each other represent hydrogen or lower alkyl;
R13represents lower alkyl;
R2represents hydrogen; or
R1and R2together with the nitrogen atom to which they are attached, form morpholinyl ring;
R15selected from the group consisting of lower alkoxyalkyl, cycloalkyl and furanyl, substituted with halogen;
R17selected from the group consisting of hydrogen, lower alkyl and lower halogenoalkane;
R4and R8independently from each other represent hydrogen or halogen;
R5and R7independently from each other selected from the group consisting of hydrogen, lower alkyl, lower alkoxy, halogen, lower halogenoalkane, lower halogenoalkane and qi is but;
R6selected from the group consisting of hydrogen, lower alkoxy, halogen, lower halogenoalkane, lower halogenoalkane and cyano;
and their pharmaceutically acceptable salts.



 

Same patents:

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of formula where R1 denotes C1-C6alkyl; W denotes pyrazolyl, triazolyl or imidazolyl; R14 denotes phenyl or a 6-member heteroaromatic ring containing 1-3 nitrogen ring atoms, which is may be substituted with at least one substitute selected from F, Cl, CN and CF3; R3 denotes phenyl, substituted with a trifluoromethyl substitute; R4 denotes hydrogen or C1-C6alkyl; X denotes -C1-C6alkylene-Y-, and Y denotes a single bond, and the alkylene group is a straight or branched C1-C6alkylene, possibly substituted with OH, CO2R66 or C1-C3alkoxy; R5 denotes phenyl or pyridinyl, substituted with -S(O)vR21; or R5 denotes an unsubstituted C3-C6cycloalkyl ring; or R5 can also denote H; R21 denotes hydrogen, C1-C6alkyl or C3-C8cycloalkyl; v equals 1 or 2; and R66 denotes hydrogen or C1-C6alkyl; or pharmaceutically acceptable salts thereof. The invention also relates to a method of producing said compounds, intermediate compounds and a pharmaceutical composition for treating or reducing the risk of disease or condition, in which inhibiting neutrophil elastase activity based on compounds of formula (I) is useful.

EFFECT: obtaining novel compounds which can be used in medicine to treat or reduce the risk of disease or condition in which inhibiting neutrophil elastase activity is useful.

19 cl, 16 ex

FIELD: chemistry.

SUBSTANCE: present invention refers to the compound 5-[3-[(2S)-1-(difluoromethoxy)-propane-2-yl]-oxy-5-[(5-methylpyrazin-2-yl)-carbamoyl]]phenoxy]-N,N-dimethyl-pyrazine-2-carboxamide. The invention also refers to a pharmaceutical composition, and also to application of the compound under cl.1.

EFFECT: making the new biologically active compounds showing GLK (glucokinase) activator activity.

5 cl, 6 ex, 2 tbl, 2 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: described is 2-alkyl-cycloalk(en)yl-carboxamides of formula

, in which X, s, R1 , L, R2 and A assume values given in the formula of invention, a method of producing said compounds, an agent and use of said compounds against unwanted microorganisms.

EFFECT: higher activity compared to existing compounds, low toxicity and high toleration by plants.

6 cl, 8 tbl, 6 ex

FIELD: chemistry.

SUBSTANCE: present invention relates to hot or sweet flavourants in form of a synthetic amide compound or edible salt thereof in amount ranging from approximately 0.001 parts per million to approximately 100 parts per million. The amide compound has formula

where A is a phenyl or a 5- or 6-member heteroaryl ring selected from a group comprising pyridine, pyrazine, pyrazole, thiazole, furan, thiophene, benzofuran and benzothiophene; m equals 1, 2 or 3, each R1 is independently selected from hydroxyl, fluorine, chlorine, SEt, SCH3, methyl, ethyl, isopropyl, vinyl, trifluoromethyl, methoxy, ethoxy and isopropoxy, or alternatively two R1 are bonded to form a saturated C1-C3 alkylenedioxy ring on the phenyl; and R2 is a C3-C10 branched alkyl. The amide compound also has formula

in which substitutes A, B, R50, R60, R70, R80, n and m assume values given in the formula of invention. The amide compound is also a specific chemical compound.

EFFECT: obtaining hot and sweet taste modifiers and boosters for food and medicinal products.

39 cl, 7 tbl, 180 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to compound of formula 2: and to its pharmaceutically acceptable salts and their mixtures, where values of R, M, Q, Z, W, D radicals are described in i.1 of the invention formula. Invention also relates to pharmaceutical compositions, which possess inhibiting activity with respect to Btk, based on formula 2 compounds.

EFFECT: obtained are novel compounds and based on them pharmaceutical compositions which can be applied in medicine for treatment of patients with diseases associated with inhibiting Btk activity and/or B-cell activity.

55 cl, 19 ex

FIELD: chemistry, pharmacology.

SUBSTANCE: invention relates to novel compounds -acidified arylcycloalkylamins of formula I in any of their stereoisomeric forms or in form of their mixture in any ratio, or their pharmaceutically acceptable salts, where in formula I : R1 represents aryl, not obligatory substituted with one or two similar or different substitutes, selected from group that includes C1-C6-alkyl and halogen; R2 represents aryl or heteroaryl, which represents residue of 5-6-member aromatic monocyclic heterocycle, containing 1-2 nitrogen atoms as heteroatom and/or 1 sulfur atom or oxygen atom, or residue of 9-10-member aromatic bicyclic heterocycle, containing 1-2 nitrogen atoms as heteroatom, each of which is unsubstituted or contains 1-3 similar or different substitutes, selected from group, consisting of halogens, NH2, unsubstituted C1-C10-alkyl, C1-C10 -alcoxy, C1-C10-alkylamino and di(C1-C10-alkyl)amino, and at least monosubstituted C1-C10-alkyl, etc., n represents 1, 2, 3 or 4. Invention relates to pharmaceutical composition, stimulating expression of endothelial NO synthase, based on said compounds, as well as application of compounds of formula I for production of medication for stimulating expression of endothelial NO-synthase and for treatment of such cardiovascular diseases as atherosclerosis, thrombosis, coronary artery disease, hypertension and impaired cardiac function.

EFFECT: invention ensures enhancing composition and treatment method efficiency.

9 cl, 2 tbl, 41 ex

FIELD: medicine, pharmacy.

SUBSTANCE: invention relates to new acid-additive nitrate salts of compounds taken among salbutamol, cetirizine, loratidine, terfenadine, emedastine, ketotifen, nedocromil, ambroxol, dextrometorphan, dextrorphan, isoniazide, erythromycin and pyrazinamide. Indicated salts can be used for treatment of pathology of respiratory system and elicit an anti-allergic, anti-asthmatic effect and can be used in ophthalmology also. Indicated salts have less adverse effect on cardiovascular and/or gastroenteric systems as compared with their non-salt analogues. Also, invention proposes pharmaceutical compositions for preparing medicinal agents for treatment of pathology of respiratory system and comprising above indicated salts or nitrate salts of metronidazol or aciclovir.

EFFECT: improved and valuable properties of compounds.

6 cl, 5 tbl, 19 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to a new compound of formula A

the radicals R1, R2, R3, R4, R5, R25, R26, U, T, W, V, Y are those as specified in clause 1 of the patent claim. Also, the invention refers to a method for preparing the compound of formula A, the drug based on this compound applied for treating disorders or diseases which are at least partially mediated by vanilloid receptor VR1 /NRPV1, as well as use of this compound for preparing the drug.

EFFECT: there are prepared and described new compounds which can be effective in treating diseases which are at least partially mediated by vanilloid receptor VR1 /NRPV1.

43 cl, 367 ex, 4 tbl

FIELD: medicine, pharmaceutics.

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

wherein: A means a ring selected from phenyl group or heteroaryl group, Q means oxygen atom or a link -CH2-, X, Y and Z mean carbon atoms; R1 and R2, identical or different are selected from the following atoms and groups: hydrogen, halogen, -CF3, (C1-C6)alkyl, Alk, (C1-C6)alkoxy, (C1-C6)alkyl-O-(C1-C6)alkyl, -(CH2)m-SO2-(C1-C6)alkyl with m equal to 0, 1 or 2, benzyl, pyrazolyl, -CH2-triazolyl and -L-R12 wherein L represents a link or a bridge -CH2- and/or -CO- and/or -SO2-, and R12 means (C3-C8)cycloalkyl or group of formula ,

wherein: n=0 or 1, R13 means one-three groups, identical or different, selected from hydrogen atom and hydroxyl, (C1-C4)alkyl, oxo and phenyl, R14 means hydrogen atom or is selected from groups - NR18R19, -NR18-COOR19, -NR18-Alk-R20 and -R21, wherein R18, R19, R20, R21 and Alk have the values as specified below, R14' means -CO-(C1-C6)alkyl, R15 is selected from groups -Alk, -R20, -Alk-R20, -Alk-R21, -CO-Alk, -CO-R20, -CO-R21, -Alk-CO-NR18R19, (C3-C8)cycloalkyl and -CO-(C3-C8)cycloalkyl, wherein R18, R19, R20, R21 and Alk has the values as specified below, R16 means hydrogen atom or group Alk, wherein Alk has the values as specified below, R17 means group -Alk, -Alk-R20 or -Alk-R21, wherein Alk, R20 and R21 have the values as specified below, -CO-(C1-C6)alkyl, -CO-(C3-C8)cycloalkyl, R18 and R19, identical or different, mean hydrogen atom or (C1-C6)alkyl, R20 means phenyl or heteroaryl group (such as pyridinyl, pyrazolyl, pyrimidinyl or benzimidazolyl), which is optionally substituted by one (C1-C6)alkyl, R21 means heterocycloalkyl group optionally substituted by one or more halogen atoms or (C1-C6)alkyl, hydroxyl or (C1-C4)alkoxy groups, and Alk means (C1-C6)alkyl which is linear or branched and which is optionally substituted by one or two groups, identical or different, selected from hydroxyl, phenyl, (C1-C4)alkoxy and -NR18R19, wherein R18 and R19 have the values as specified above, R3 means linear (C1-C10)alkyl which is optionally substituted by one-three groups, identical or different, selected from halogen atoms and (C1-C4)alkoxy groups, R4 means hydrogen atom, R5 and R6 independently mean hydrogen atom or (C1-C5)alkyl, R7 and R8 independently mean hydrogen atom or (C1-C5)alkyl, R9 and R10 independently mean hydrogen atom, or R9 and R10 together form linear (C2-C3)alkylene chain, thereby forming 6-merous ring with nitrogen atom whereto attached with said alkylene chain optionally substituted by one-three groups selected from (C1-C4)alkyl, oxo, R11 means hydrogen atom or (C1-C8)alkyl which is optionally substituted by one-three groups selected from halogen atoms, hydroxyl, (C1-C6)alkoxy, -NR18R19, - or pyridinyl, wherein R18 and R19 have the values as specified above; wherein 'heterocyclic group' means saturated 5- or 6-member ring containing one or two heteroatoms selected from oxygen, nitrogen and sulphur atoms; 'heteroaryl group' means aromatic cyclic group containing 5-11 ring atoms selected from carbon, nitrogen and sulphur atoms with heteroaryl groups to be monocyclic or bicyclic, in this case at least one of two cyclic fragments are aromatic; in the form of a free base or an additive acid salt or base. Also, the invention refers to methods for preparing such compounds and to a based drug showing rennin inhibitory activity.

EFFECT: compounds can find application in medicine for preparing the drug for treating and preventing hypertension, cardiac damages, myocardial infraction, cardiac failure, cardiac and vascular hypertrophy, left ventricular dysfunction, restenosis, glaucoma, renal conditions, diabetic complications.

26 cl, 3 tbl, 18 ex

FIELD: chemistry.

SUBSTANCE: present invention refers to new compounds of formula I-9 where q is represented by 1; R11 is represented by C3-8-alkyl; C3-8-cycloalkyl or C3-8-cycloalkyl-C1-3-alkyl; A is represented by phenyl substituted by one or more substituting groups independently chosen from R12; and R12 is represented by -(CH2)-NR13R14; R13 is represented by C1-6-alkylcarbanil; and R14 is represented by hydrogen; and to the pharmaceutically acceptable salts of such compounds and to the pharmaceutical compositions based on such compounds. It has been revealed that the compounds of formula I-9 are histamine NZ-receptor antagonists and thus that they can be used in treatment of diseases connected with expression of such receptors.

EFFECT: compounds of formula I-9 can be used in treatment of diseases connected with expression of histamine NZ-receptors.

6 cl, 216 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: present invention is related to compounds of general formula (I) where: R1 and R2 either identical or the same represent: hydrogen atom or halogen atom, CN or NO2, with R1 and R2 being other than hydrogen atom simultaneously; m means: 1 or 2, n means: 0, 1 or 2; R3 represents: phenyl radical either substituted or unsubstituted by one or more radical selected halogen atom, hydroxyl group or C1-C6 alkyl group; C2-C6 alkyl group either substituted or unsubstituted by one or more radicals selected from halogen atom or hydroxyl group; cycloalkyl group; pyridine; thiophene; pyrrole either substituted or unsubstituted by C1-C6 alkyl group; thiazole or furan; or to therapeutically acceptable salts or solvates.

EFFECT: invention refers to methods for preparing the compounds of formula I, to based pharmaceutical compositions showing antithrombotic activity, as well as to the use of these compounds for preparing a antiaggregant.

11 cl, 36 ex

FIELD: chemistry.

SUBSTANCE: invention relates to compounds selected from a group comprising piperazine compounds of formula I: , where X is -CH2- or a bond; n equals 1; R1 is alkyl; cycloakyl; hydroxyethyl; benzo[1,3]dioxolyl; phenyl, which can be mono-substituted with a halide, alkyl, alkoxy, -CF3 or alkylcarbonyl; or phenyl which is di- or tri-substituted with substitutes independently selected from alkyl and halide; pyridyl which can be mono-substituted with a halide, alkyl or -CF3; furanyl which can be mono-substituted with methyl, hydroxymethyl or bromine, or furanyl which is disubstituted with an alkyl; thienyl which can be mono-substituted with methyl or chromium; pyrimidinyl; isoquinolinyl; benzhydryl; imidazolyl optionally mono-substituted with an alkyl; or thiazolyl; or X is -C(=O)- and R1 is hydrogen; R2 is indolyl, imidazolyl optionally mono-substituted with alkyl; phenyl which can be mono-substituted with a halide, alkyl, hydroxy or cyano, or phenyl which is disubstituted with a halide; pyridyl; benzothienyl; thiazolyl or thienyl; R3 is indolyl, pyridyl which can be mono-substituted with alkoxy, alkoxyalkoxy, NR31R32, morpholine, piperadine, oxopiperidinyl, oxopyrrolidinyl, pyridyl or phenyl; or phenyl which is mono-substituted with phenyl, pyridyl, alkyl, alkoxy, dialkylamino, morpholine, N-benzyl-N-alkylamino, (dialkylamino)alkoxy, phenylalkoxy or tetrahydroisoquinolinyl; or R3 denotes the group: , where Z is phenyl or pyridyl; R31 is 2-C1-C5alkoxyethyl, phenyl, pyridyl, phenylalkyl, hydroxyalkylcarbonyl, alkylcarbonyl, cycloalkylcarbonyl or phenylcarbonyl; R32 is hydrogen or methyl; R35 is alkyl, alkylcarbonyl, phenyl, pyridyl or pyrimidinyl; and R4 is phenyl-CH=CH-, where the phenyl can be mono-, di- or tri-substituted with substitutes independently selected from halide, alkyl, alkoxy and -CF3; or phenyl-CH2-CH2, where the phenyl is disubstituted with -CF3; and to optically pure enantiomers thereof, mixtures of enantiomers, such as, for example, racemates, optically pure diastereomers, mixtures of diastereomers, diastereomeric racemates, mixtures of diastereomeric racemates and mesoforms, such as salts of such compounds. The invention also relates to a pharmaceutical composition, as well as to use of compounds in any of claims 1-4.

EFFECT: obtaining novel biologically active compounds with antimalarial activity.

8 cl, 138 ex, 1 tbl

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to compound of formula 2: and to its pharmaceutically acceptable salts and their mixtures, where values of R, M, Q, Z, W, D radicals are described in i.1 of the invention formula. Invention also relates to pharmaceutical compositions, which possess inhibiting activity with respect to Btk, based on formula 2 compounds.

EFFECT: obtained are novel compounds and based on them pharmaceutical compositions which can be applied in medicine for treatment of patients with diseases associated with inhibiting Btk activity and/or B-cell activity.

55 cl, 19 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a new improved method of producing onium tetrafluoroborates through reaction of an onium halide with trialkyloxonium tetrafluoroborate, trialkylsulphonium tetrafluoroborate or triphenylcarbonium tetrafluoroborate, characterised by that the halide has formula (1) [XR4]+ Hal-, where X denotes N, P, Hal denotes Cl, Br or I and R in each case independently denotes a linear alkyl having 1-8 C atoms, or the halide has formula (2) [(R1R2N)-C(=SR7)(NR3R4)]+ Hal- (2), where Hal denotes Br or I R1-R7 each independently denotes a linear alkyl having 1-8 C atoms, or the halide has formula (3) [C(NR1R2)(NR3R4)(NR5R6)]+ Hal- (3), where Hal denotes CI, Br or I and R1-R6 each independently denotes a linear alkyl having 1-8 C atoms, or the halide has formula (4) [HetN]+ Hal- , where Hal denotes CI, Br or I and HetN+ denotes a heterocyclic cation selected from a group comprising imidazolium pyrrolidinium pyridinium where each of substitutes R1' - R4' independently denotes hydrogen, CN, linear or branched alkyl having 1-8 C atoms, dialkylamine containing alkyl groups having 1-4 C atoms but which is not attached to he heteroatom of the heterocyclic ring.

EFFECT: method enables to obtain products with low content of halides with high purity and high output.

5 cl, 12 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to novel amide derivatives of general formula [1] in any of versions (A) or (B), or its pharmaceutically acceptable salt, which possess properties of tyrosinkinase BCR-ABL inhibitor. Amide derivative of general formula [1] represents compound: , where according to Version (A) R1 represents any of the following groups (1)-(3): (1) -) -CH2-R11 [R11 represents saturated 4-6 member nitrogen-containing heterocyclic group, optionally containing additional nitrogen atom; saturated 5-6-member nitrogen-containing heterocyclic group, optionally containing additional nitrogen atom, which is substituted by group selected from group, consisting of oxo, -CH2-R111 (R111 represents saturated 5-member nitrogen-containing heterocyclic group), saturated 5-member nitrogen-containing heterocyclic group, aminomethyl, monoalkylaminomethyl, dialkylaminomethyl and (5-methyl-2-oxo-1,3-Dioxol-4-yl)methyl, and in addition, can be substituted by 1 or 2 similar or different substituents, selected from group, consisting of (C1-C4)alkyl, (C1-C4 alkoxycarbonyl, halogen, halogen(C1-C4)alkyl, hydroxy(C1-C4)alkyl, amino, carbamoyl], (2) -O-R12 [R12 represents saturated 4-6-member nitrogen-containing heterocyclic group]; and (3) - CH=R13 [R13 represents saturated 4-6-member nitrogen-containing heterocyclic group, which can contain additional nitrogen atom, and which can be substituted by 1-3 similar or different substituents, selected from group, consisting of oxo, (C1-C4)alkyl]; R2 represents (C1-C4)alkyl, halogen, halogen(C1-C4)alkyl, hydroxy(C1-C4)alkyl, (C1-C4)alkoxy and carbamoyl; R3 represents hydrogen, halogen; Het1 represents any of groups with the following chemical formulae [4] and [6]: [4] [6] [19] [10] Het2 represents pyridyl or pyrimidinyl. According to Version (B) R1 represents -CH2-R14 [R14 represents saturated 4-6-member nitrogen-containing heterocyclic group, optionally containing additional nitrogen atom; saturated 5-6-member nitrogen-containing heterocyclic group, which can be substituted by 1-3 similar groups, selected from (C1-C4)alkyl] R2 represents (C1-C4)alkyl, halogen, halogen(C1-C4)alkyl, hydroxy(C1-C4)alkyl, (C1-C4)alkoxy, (C1-C4)alkoxy (C1-C4)alkyl, (C1-C4)alkoxycarbonyl, (C1-C4)acyl, amino, mono(C1-C4)alkylamino, di(C1-C4)alkylamino, nitro, carbamoyl, mono(C1-C4)alkylcarbamoyl, di(C1-C4)alkylcarbamoyl or cyano; R3 represents hydrogen or halogen; Het1 represents any of groups with the following chemical formulas [9] and [10], Het2 represents pyridyl.

EFFECT: invention can be applied for treatment of chronic myeloleukosis, acute lymphoblastic leukosis and acute myeloblastic leukosis.

6 cl, 89 ex, 3 tbl

FIELD: medicine, pharmaceutics.

SUBSTANCE: claimed invention relates to derivatives of (R)-2-arylpropionamides of general formula I, in which Ar is phenyl group, substituted in 3(meta) position by group R1, selected from: linear or branched C1-C8-alkanoyl, C3-C6- cycloalkanoyl, heteroarylcarbonyl, C1-C6-alkylaminocarbonyl, arylaminocarbonyl, C1-C6-alkylamino, C1-C6-acylamino, arylamino, benzoylamino, aryloxy, heteroaryl, C1-C6-alkoxycarbonyl, C6-aryloxycarbonyl, C1-C8-alkansulfonyl, arylsulfonyl, or 3,4-dihydro-1H-quinolyl-2-on; R is selected from: -H, OH; - heteroaryl group is selected from: pyridine, pyrimidine, pyrrole, thiophene, furan, indole, thiazole, oxazole; - α or β carboxyl residue can consist of straight or branched C1-C6-alkyl, C3-C6-cycloalkyl, optionally substituted with other carboxyl (COOH) group; - residue with formula SO2Rd, in which Rd is C1-C6-alkyl, C3-C6-cycloalkyl, C2-C6-alkenyl or pyridyl, on condition that compounds of formula I are not the following compounds: (R)-2-(3-phenoxyphenyl)-propanoyl-phenylglycine; (R)-2-( phenoxyphenyl)-propanoyl-glycine; (R)-2-[(3'-acetyl)phenyl]-R-4''-pyrimidyl)propionamide. Invention also relates to method of obtaining formulaI compound and application of formula I compound for preparation of medications for treatment of diseases including C5a induced hemotaxis of human PMNs.

EFFECT: obtained are novel derivatives of (R)-2-arylpropionamide, possessing useful biological properties.

9 cl, 3 dwg, 2 tbl, 34 ex

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of formula: ,

where R1 is selected from a group consisting of cycloalkyl which is unsubstituted or substituted with hydroxy or lower alkoxy, lower hydroxylalkyl, lower hydroxyhalogenalkyl, -CH2-CR9R10-cycloalkyl; R9 is hydrogen or lower alkyl; R10 is hydrogen, hydroxy or lower alkoxy; R2 is hydrogen; X is O or NR14; R14 is hydrogen or lower alkyl; R3 is selected from a group consisting of lower alkyl, cycloalkyl, lower cycloalkylalkyl, lower alkoxyalkyl, lower halogenalkyl, lower carbamoylalkyl, lower phenylalkyl, lower heterocyclylalkyl, where the heterocyclyl is a saturated 4- or 5-member ring containing one or two oxygen atoms, lower heteroarylalkyl, where the heteroaryl group is unsubstituted or mono- or disubstituted with a halogen, and phenyl which is unsubstituted or mono- or disubstituted with a halogen; or R3 and R14 together with a nitrogen atom to which they are bonded form an N-heterocyclic ring selected from pyrrolidinyl, piperidinyl or azepanyl; R4 and R8 independently denote hydrogen or halogen; R5 and R7 are independently selected from a group consisting of hydrogen, halogen, lower halogenalkyl, lower halogen, alkoxy and cyano; R6 is selected from a group consisting of hydrogen, halogen, lower halogenalkyl, lower halogen alkoxy and cyano; and pharmaceutically acceptable salts thereof, as well as to a pharmaceutical composition based on said compounds, which has CB1 modulating activity.

EFFECT: novel compounds which can be used to treat and prevent diseases associated with modulation of CB1 receptors, such as obesity, are obtained and described.

23 cl, 153 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to polymorphic forms of (2S)-(4E)-N-methyl-5-[3-(5-isopropoxypyridin)yl]-4-penten-2- amine of "п"-hydroxybenzoate, to pharmaceutic composition, containing said polymorph(s), as well as to their application for treatment of CNS disorders.

EFFECT: obtained and described are novel polymorphic forms of (2S)-(4E)-N-methyl-5-[3-(5-isopropoxypyridin)yl]-4-penten-2-amine of "п"-hydroxybenzoate, which can be applied to patients, subjected or possessing diseases and disorders, such as central nervous system diseases, for treatment and/or prevention such disorders

13 cl, 4 ex, 2 tbl

Up!