Bridge six-member cyclic compounds

FIELD: chemistry.

SUBSTANCE: invention relates to organic chemistry and specifically to compounds of formula or a pharmaceutically acceptable salt of such a compound, where - X is a carbon atom and R1a and R2a together form a bond; or - X is a carbon atom, R1a and R2a together form a bond, and R1 and R2 together form a moiety , where the asterisk shows the bonding site of R2; or - X is a carbon atom, R1a is hydrogen or (C1-4)alkoxy, and R2a is hydrogen; and R1 and R2, unless indicated otherwise, independently denote hydrogen; (C1-5)alkyl; aryl, where aryl denotes naphthyl or phenyl, where said aryl is unsubstituted or independently mono- or disubstituted, where the substitutes are independently selected from a group consisting of (C1-4)alkyl, (C1-4) alkoxy and halogen; or heteroaryl, selected from pyridyl, thienyl, oxazolyl or thiazolyl, where said heteroaryl is unsubstituted; under the condition that if R2 is aryl or heteroaryl, R1 cannot be aryl or heteroaryl, where the aryl and heteroaryl are independently unsubstituted or substituted as defined above; R3 is hydrogen or -CO-R31; R31 is (C1-5)alkyl, (C1-3)fluoroalkyl or (C3-6)cycloalkyl; n equals 1, 2, 3 or 4; B is a -(CH2)m- group, where m equals an integer from 1 to 3; A is-(CH2)P-, where p equals 2 or 3; R4 is (C1-5)alkyl; W is , where R5 is hydrogen or (C1-5)alkyl; R8, R9 and R10 is independently hydrogen, halogen, (C1-5)alkyl, hydroxy, -(C1-5)alkoxy, -O-CO-(C1-5)alkyl, (C1-3)fluoroalkyl, (C1-3)fluoroalkoxy, -CO-(C1-5)alkoxy, (C1-2)alkoxy-(C1-4)alkoxy or -NH-CO-(C1-5)alkyl. The invention also relates to a pharmaceutical composition based on a compound of formula (I).

EFFECT: novel compounds which are useful as calcium channel blockers are obtained.

11 cl, 2 tbl, 166 ex

 

The text descriptions are given in facsimile form.

1. The compound of formula (I):

where X represents a carbon atom, and R1aand R2atogether form a bond; or
X represents a carbon atom, R1aand R2atogether form a bond, and R1and R2together form the fragment
,
where the asterisk shows the connection point R2; or
X represents a carbon atom, R1arepresents hydrogen or (C1-4)alkoxy, and R2arepresents hydrogen; and
R1and R2unless otherwise noted, independently represent hydrogen; (C1-5 )alkyl; aryl, where aryl means a naphthyl or phenyl, where the specified aryl is unsubstituted or independently mono - or disubstituted where the substituents are independently selected from the group consisting of (C1-4)alkyl, (C1-4) alkoxy and halogen; or heteroaryl selected from pyridyl, teinila, oxazolyl and thiazolyl where specified heteroaryl is unsubstituted; provided that when R2represents aryl or heteroaryl, R1may not represent aryl or heteroaryl, where aryl and heteroaryl independently are unsubstituted or substituted as defined above;
R3represents hydrogen or-CO-R31;
R31is a (C1-5)alkyl, (C1-3)foralkyl or (C3-6)cycloalkyl;
n is an integer 1, 2, 3 or 4;
Represents a group -(CH2)m-where m is an integer from 1 to 3;
And represents -(CH2)p-where p is an integer 2 or 3;
R4is a (C1-5)alkyl;
W represents a

where R5represents hydrogen or (C1-5)alkyl;
R8, R9and R10independently represent hydrogen, halogen, (C1-5)alkyl, hydroxy, (C1-5)alkoxy, -O-CO-(C1-5)alkyl, (C1-3)foralkyl, (C1-3)feralcode, -CO-(C1-5)alkoxy, (the 1-2)alkoxy-(C1-4)alkoxy, or-NH-CO-(C1-5)alkyl;
or pharmaceutically acceptable salt of such compounds.

2. The compound of formula (I) according to claim 1, where the configuration of the bridge cyclohexane or cyclohexanol group is such that R3About the Deputy and the bridge And the cyclohexane or cyclohexanol groups are in CIS-position; or a pharmaceutically acceptable salt of such compounds.

3. The compound of formula (I) according to claim 2, where X represents a carbon atom; R1aand R2atogether form a bond; R1represents phenyl, which is unsubstituted, mono - or disubstituted where the substituents are independently selected from the group consisting of (C1-4)alkyl, (C1-4)alkoxy and halogen; or R1represents an unsubstituted heteroaryl selected from pyridyl, teinila, oxazolyl and thiazolyl; and R2represents hydrogen or (C1-5)alkyl; or a pharmaceutically acceptable salt of such compounds.

4. The compound of formula (I) according to any one of claims 1 to 3, where R3represents a-CO-R31; and R31is a (C1-5)alkyl, (C1-3)foralkyl or (C3-6)cycloalkyl; or a pharmaceutically acceptable salt of such compounds.

5. The compounds of formula (I) according to claim 4, where n is an integer 2; or a pharmaceutically acceptable salt of such compounds.

6. The compound of formula (I) according to claim 5, where W is a

where R5represents hydrogen or (C1-5)alkyl;
R8, R9and R10independently represent hydrogen, halogen, (C1-5)alkyl, (C1-5)alkoxy, (C1-3)foralkyl or (C1-3)feralcode;
or pharmaceutically acceptable salt of such compounds.

7. The compound of formula (I) according to claim 6, where W is a
;
where R8and R10independently represent a (C1-5)alkoxy, and R5and R9represent hydrogen;
or pharmaceutically acceptable salt of such compounds.

8. The compound of formula (I) according to claim 1, selected from the following compounds:
(1R*,2R*,4R*)-2-(2-{[3-(1H-benzoimidazol-2-yl)propyl]methylamino}ethyl)-5-Panevezio[2.2.2]Oct-5-EN-2-ol;
(1R*,2R*,4R*)-2-(2-{[3-(1H-benzoimidazol-2-yl)propyl]methylamino}ethyl)-5-naphthalen-2-albicilla[2.2.2]Oct-5-EN-2-ol;
(1S,2S,4S)-2-(2-{[3-(1H-benzoimidazol-2-yl)propyl]methylamino}ethyl)-5-Panevezio[2.2.2]Oct-5-EN-2-ol;
(1R,2R,4R)-2-(2-{[3-(1H-benzoimidazol-2-yl)propyl]methylamino}ethyl)-5-Panevezio[2.2.2]Oct-5-EN-2-ol;
(1R*,2R*,4R*)-2-(2-{[2-(1H-benzoimidazol-2-yl)ethyl]methylamino}ethyl)-5-Panevezio[2.2.2]Oct-5-EN-2-ol;
(1R*,2R*,4R*)-2-{2-[(1H-benzoimidazol-2-ylmethyl)methylamino]ethyl}-5-Panevezio[2.2.2]Oct-5-EN-2-ol;
(1R*,2R*,4R*)-2-(2-{[3-(1H-benzoimidazol-2-yl)propyl]meth is a melamine}ethyl)-6-methyl-5-propylbenzyl[2.2.2]Oct-5-EN-2-ol;
(1R*,2R*,4R*)-2-(2-{[3-(1H-benzoimidazol-2-yl)propyl]methylamino}ethyl)-5-methyl-6-Panevezio[2.2.2]Oct-5-EN-2-ol;
(1R*,2S*,4R*)-2-(2-{[3-(1H-benzoimidazol-2-yl)propyl]methylamino}ethyl)-5-methyl-6-Panevezio[2.2.2]Oct-5-EN-2-ol;
(1R*,3R*,4R*)-1,2,3,4,9,10-hexahydro-3-hydroxy-3-{N-methyl-N-(3-benzoimidazol-2-ylpropyl)aminoethyl}-1,4-ethnogenetic;
methyl ester of 2-(3-{[2-((1R*,2R*,4R*)-2-hydroxy-5-Panevezio[2.2.2]Oct-5-EN-2-yl)ethyl]methylamino}propyl)-1H-benzoimidazol-4-carboxylic acid;
(1R*,2R*,4R*)-2-(2-{[3-(1H-benzoimidazol-2-yl)propyl]methylamino}ethyl)-5-(3-methoxyphenyl)bicyclo[2.2.2]Oct-5-EN-2-ol;
methyl ester of 2-(3-{[2-((1R*,2R*,4R*)-2-hydroxy-5-Panevezio-[2.2.2]Oct-5-EN-2-yl)ethyl]methylamino}propyl)-1H-benzoimidazol-5-carboxylic acid;
(1R*,2R*,4R*)-2-(2-{[3-(1H-benzoimidazol-2-yl)propyl]methylamino}ethyl)-5-thiophene-2-albicilla[2.2.2]Oct-5-EN-2-ol;
(1R*,2R*,4R*)-2-(2-{[3-(1H-benzoimidazol-2-yl)propyl]methylamino}ethyl)-5-(4-methoxyphenyl)bicyclo[2.2.2]Oct-5-EN-2-ol;
(1R*,2R*,4R*)-2-(2-{[3-(1H-benzoimidazol-2-yl)propyl]methylamino}ethyl)-5-(2-methoxyphenyl)bicyclo[2.2.2]Oct-5-EN-2-ol;
(1R*,2R*,4R*)-2-(2-{[3-(1H-benzoimidazol-2-yl)propyl]methylamino}ethyl)-5-thiazol-2-albicilla[2.2.2]Oct-5-EN-2-ol;
(1R*,2R*,4R*)-2-(2-{[3-(1H-benzoimidazol-2-yl)propyl]methylamino}ethyl)-5-oxazol-2-albicilla[2.2.2]Oct-5-EN-2-ol;
(1R*,2R*,4R*)-2-(2-{[3-(4-methoxy-1H-benzoimidazol-2-yl)propyl]-methylamino}ethyl)-5-Panevezio[2.2.2]Oct-5-EN-2-ol;
(1R*,2R*,4R*)-2-(2-{[3-(5,6-dichloro-1H-benzoimidazol-2-yl)propyl-methylamino}ethyl)-5-Panevezio[2.2.2]Oct-5-EN-2-ol;
(1R*,2R*,4R*)-2-(2-{[3-(5,6-dimethoxy-1H-benzoimidazol-2-yl)propyl]-methylamino}ethyl)-5-Panevezio[2.2.2]Oct-5-EN-2-ol;
(1R*,2R*,4R*)-2-(2-{[3-(5-methoxy-1H-benzoimidazol-2-yl)propyl]-methylamino}ethyl)-5-Panevezio[2.2.2]Oct-5-EN-2-ol;
(1R*,2R*,4R*)-2-(2-{[3-(1H-benzoimidazol-2-yl)propyl]methylamino}ethyl)-5-(2,6-dimetilfenil)bicyclo[2.2.2]Oct-5-EN-2-ol;
(1R*,2R*,4R*)-2-(2-{[3-(7-methoxy-4-methyl-1H-benzoimidazol-2-yl)-propyl]methylamino}ethyl)-5-Panevezio[2.2.2]Oct-5-EN-2-ol;
(1R*,2R*,4R*)-2-(2-{[3-(7-ethoxy-1H-benzoimidazol-2-yl)propyl]-methylamino}ethyl)-5-Panevezio[2.2.2]Oct-5-EN-2-ol;
(1R*,2R*,4R*)-2-(2-{[2-(4-methoxy-1H-benzoimidazol-2-yl)ethyl]-methylamino}ethyl)-5-Panevezio[2.2.2]Oct-5-EN-2-ol;
(1R*,2R*,4R*)-2-(2-{[3-(7-isopropoxy-1H-benzoimidazol-2-yl)propyl]-methylamino}ethyl)-5-Panevezio[2.2.2]Oct-5-EN-2-ol;
2-(3-{[2-((1R*,2R*,4R*)-2-hydroxy-5-Panevezio[2.2.2]Oct-5-EN-2-yl)ethyl]methylamino}propyl)-3H-benzoimidazol-4-ol;
(1R*,5R*,6R*)-6-(2-{[3-(7-methoxy-1H-benzoimidazol-2-yl)propyl]-methylamino}ethyl)-8-Panevezio[3.2.2]non-8-EN-6-ol;
(1R*,2R*,4R*)-2-(2-{[3-(4-methoxy-1-methyl-1H-benzoimidazol-2-yl)-propyl]methylamino}ethyl)-5-Panevezio[2.2.2]Oct-5-EN-2-ol;
(1R*,2R*,4R*)-2-(2-{[3-(1H-benzoimidazol-2-yl)propyl]methylamino}ethyl)-5-o-televizija[2.2.2]Oct-5-EN-2-ol;
(1R*,2R*,4R*)-2-(2-{[3-(1H-benzoimidazol-2-yl)propyl]methylamino}ethyl)-5-m-televizija[2.2.2]Oct-5-EN-2-ol;
(1S,2S,4S)-2-(2-{[3-(4-methoxy-1H-benzoimidazol-2-yl)propyl]-methylamino}ethyl)-5-Panevezio[2.2.2]Oct-5-EN-2-ol;
(1R,2R,4R)-2-(2-{[3-(4-methoxy-1H-benzoimidazol-2-yl)propyl]-methylamino}ethyl)-5-Panevezio[2.2.2]Oct-5-EN-2-ol;
N-[2-(3-{[2-((1R*,2R*,4R*)-2-hydroxy-5-Panevezio[2.2.2]Oct-5-EN-2-yl)ethyl]methylamino}propyl)-1H-benzoimidazol-4-yl]ndimethylacetamide;
(1R*,2R*,4R*)-2-(2-{[3-(4-chloro-1H-benzoimidazol-2-yl)propyl]-methylamino}ethyl)-5-Panevezio[2.2.2]Oct-5-EN-2-ol;
(1R*,2R*,4R*)-2-(2-{[3-(7-chloro-4-methoxy-1H-benzoimidazol-2-yl)propyl]-methylamino}ethyl)-5-Panevezio[2.2.2]Oct-5-EN-2-ol;
(1R*,2R*,4R*)-2-(2-{[3-(4,6-dimethoxy-1H-benzoimidazol-2-yl)propyl]-methylamino}ethyl)-5-Panevezio[2.2.2]Oct-5-EN-2-ol;
(1R*,2R*,4R*)-2-(2-{[3-(1H-benzoimidazol-2-yl)propyl]methylamino}ethyl)-5-p-televizija[2.2.2]Oct-5-EN-2-ol;
(1S,2S,4S)-2-(2-{[3-(4,6-dimethoxy-1H-benzoimidazol-2-yl)propyl]-methylamino}ethyl)-5-Panevezio[2.2.2]Oct-5-EN-2-ol;
(1R*,2R*,4R*)-2-(2-{[3-(4,7-dimethoxy-1H-benzoimidazol-2-yl)propyl]-methylamino}ethyl)-5-Panevezio[2.2.2]Oct-5-EN-2-ol;
(1R*,2R*,4R*)-2-(2-{[3-(4,6-bis-trifluoromethyl-1H-benzoimidazol-2-yl)-propyl]methylamino}ethyl)-5-Panevezio[2.2.2]Oct-5-EN-2-ol;
(1R*,2R*,4R*)-2-[2-({3-[4-(2-methoxyethoxy)-1H-benzoimidazol-2-yl]-propyl}methylamino)ethyl]-5-Panevezio[2.2.2]Oct-5-EN-2-ol;
(1R*,2R*,4R*)-2-(2-{[3-(4,5-dimethoxy-7-methyl-1H-benzoimidazol-2-yl)-propyl]methylamino}ethyl)-5-Panevezio[2.2.2]Oct-5-EN-2-ol;
(1S,2S,4S)-2-(2-{[3-(4,5-dimethoxy-7-methyl-1H-benzoimidazol-2-yl)-propyl]methylamino}ethyl)-5-Panevezio[2.2.2]Oct-5-EN-2-ol;
(1R*,5R*,6R*)-6-(2-{[3-(7-methoxy-4-methyl-1H-benzoimidazol-2-yl)-propyl]methylamino}ethyl)-8-Panevezio[3.2.2]non-8-EN-6-ol;
(1R,2R,4R)-2-(2-{[3-(4,7-dimethoxy-1H-benzoimidazol-2-is)propyl]-methylamino}ethyl)-5-Panevezio[2.2.2]Oct-5-EN-2-ol;
(1R*,2R*,4R*)-2-(2-{methyl-[3-(4-triptoreline-1H-benzoimidazol-2-yl)-propyl]amino}ethyl)-5-Panevezio[2.2.2]Oct-5-EN-2-ol;
(1R*,2R*,4R*)-6-(2-{[3-(4,7-dimethoxy-1H-benzoimidazol-2-yl)propyl]-methylamino}ethyl)-8-Panevezio[3.2.2]non-8-EN-6-ol;
(1R*,2R*,4R*)-2-(2-{[3-(1H-benzoimidazol-2-yl)propyl]methylamino}ethyl)-5-(3-forfinal)bicyclo[2.2.2]Oct-5-EN-2-ol;
(1S,2S,4S)-2-(2-{[3-(4,7-dimethoxy-1H-benzoimidazol-2-yl)propyl]-methylamino}ethyl)-5-Panevezio[2.2.2]Oct-5-EN-2-ol;
(1R*,2R*,4R*)-2-(2-{[3-(1H-benzoimidazol-2-yl)propyl]methylamino}ethyl)-bicyclo[2.2.2]Oct-5-EN-2-ol;
(1R*,2R*,4R*,5R*)-2-(2-{[3-(1H-benzoimidazol-2-yl)propyl]metrano}-ethyl)-5-methoxy-5-Panevezio[2.2.2]Octan-2-ol;
(1R*,2S*,4R*,5R*)-2-(2-{[3-(1H-benzoimidazol-2-yl)propyl]methylamino}-ethyl)-5-methoxy-5-Panevezio[2.2.2]Octan-2-ol;
(1R*,2R*,4R*,5R*)-2-(2-{[3-(1H-benzoimidazol-2-yl)propyl]methylamino}-ethyl)-5-methoxy-5-Panevezio[2.2.2]Octan-2-ol;
(1R*,2R*,4R*)-2-(2-{[3-(1H-benzoimidazol-2-yl)propyl]methylamino}ethyl)-5-(4-forfinal)bicyclo[2.2.2]Oct-5-EN-2-ol; and
(1R*,2R*,4R*)-2-(2-{[3-(1H-benzoimidazol-2-yl)propyl]methylamino}ethyl)-5-pyridin-3-albicilla[2.2.2]Oct-5-EN-2-ol;
or pharmaceutically acceptable salt of such compounds.

9. The compound of formula (I) according to claim 1, selected from the following compounds:
(1R*,2R*,4R*)-2-(2-{[3-(1H-benzoimidazol-2-yl)propyl]methylamino}ethyl)-
5-naphthalen-2-albicilla[2.2.2]Oct-5-EN-2-silt ether isobutane acid;
(1S,2S,4S)-2-(2-{[3-(1H-benzoimidazol-2-yl)propyl]methylamino}ethyl)-5-inivisible[2.2.2]Oct-5-EN-2-silt ether isobutane acid;
(1R,2R,4R)-2-(2-{[3-(1H-benzoimidazol-2-yl)propyl]methylamino}ethyl)-5-Panevezio[2.2.2]Oct-5-EN-2-silt ether isobutane acid;
(1R*,2R*,4R*)-2-(2-{[2-(1H-benzoimidazol-2-yl)ethyl]methylamino}ethyl)-5-Panevezio[2.2.2]Oct-5-EN-2-silt ether isobutane acid;
(1R*,2R*,4R*)-2-{2-[(1H-benzoimidazol-2-ylmethyl)methylamino]ethyl}-5-Panevezio[2.2.2]Oct-5-EN-2-silt ether isobutane acid;
(1R*,2R*,4R*)-2-(2-{[3-(1H-benzoimidazol-2-yl)propyl]methylamino}ethyl)-
6-methyl-5-propylbenzyl[2.2.2]Oct-5-EN-2-silt ether isobutane acid;
(1R*,2R*,4R*)-2-(2-{[3-(1H-benzoimidazol-2-yl)propyl]methylamino}ethyl)-5-methyl-6-Panevezio[2.2.2]Oct-5-EN-2-silt ether isobutane acid;
(1R*,2S*,4R*)-2-(2-{[3-(1H-benzoimidazol-2-yl)propyl]methylamino}ethyl)-5-methyl-6-Panevezio[2.2.2]Oct-5-EN-2-silt ether isobutane acid;
(1R*,3R*,4R*)-1,2,3,4,9,10-hexahydro-3-hydroxy-3-{N-methyl-N-(3-benzoimidazol-2-ylpropyl)aminoethyl}-1,4-ethnopedology ether isobutane acid;
methyl ester of 2-(3-{[2-((1R*,2R*,4R*)-2-isobutyryloxy-5-phenyl-bicyclo[2.2.2]Oct-5-EN-2-yl)ethyl]methylamino}propyl)-1H-benzoimidazol-4-carboxylic acid;
(1R*,2R*,4R*)-2-(2-{[3-(1H-benzoimidazol-2-yl)propyl]methylamino}-ethyl)-5-Panevezio[2.2.2]Oct-5-EN-2-silt ether isobutane acid;
methyl ester of 2-(3-{[2-((1R*,2R*,4R*)-2-isobutyryloxy-5-phenyl-bicyclo[2.2.2]Oct-5-EN-2-yl)ethyl]methylamino}propyl)-1H-benzoimidazol-5-carboxylic acid;
(1R*,2R*,4R*)-2-(2-{[3-(1H-Ben is imidazol-2-yl)propyl]methylamino}ethyl)-5-thiophene-2-albicilla[2.2.2]Oct-5-EN-2-silt ether isobutane acid;
(1R*,2R*,4R*)-2-(2-{[3-(1H-benzoimidazol-2-yl)propyl]methylamino}ethyl)-5-(4-methoxyphenyl)bicyclo[2.2.2]Oct-5-EN-2-silt ether isobutane acid;
(1R*,2R*,4R*)-2-(2-{[3-(1H-benzoimidazol-2-yl)propyl]methylamino}ethyl)-5-(2-methoxyphenyl)bicyclo[2.2.2]Oct-5-EN-2-silt ether isobutane acid;
(1R*,2R*,4R*)-2-(2-{[3-(1H-benzoimidazol-2-yl)propyl]methylamino}ethyl)-5-thiazol-2-albicilla[2.2.2]Oct-5-EN-2-silt ether isobutane acid;
(1R*,2R*,4R*)-2-(2-{[3-(1H-benzoimidazol-2-yl)propyl]methylamino}ethyl)-5-oxazol-2-yl-bicyclo[2.2.2]Oct-5-EN-2-silt ether isobutane acid;
(1R*,2R*,4R*)-2-(2-{[3-(4-methoxy-1H-benzoimidazol-2-yl)propyl]-methylamino}ethyl)-5-Panevezio[2.2.2]Oct-5-EN-2-silt ether isobutane acid;
(1R*,2R*,4R*)-2-(2-{[3-(4-methoxy-1H-benzoimidazol-2-yl)propyl]-methylamino}ethyl)-5-Panevezio[2.2.2]Oct-5-EN-2-silt ether cyclobutanecarbonyl acid;
(1R*,2R*,4R*)-2-(2-{[3-(4-methoxy-1H-benzoimidazol-2-yl)propyl]-methylamino}ethyl)-5-Panevezio[2.2.2]Oct-5-EN-2-silt ester of 3,3,3-triptocaine acid;
(1R*,2R*,4R*)-2-(2-{[3-(4-methoxy-1H-benzoimidazol-2-yl)propyl]-methylamino}ethyl)-5-Panevezio[2.2.2]Oct-5-EN-2-silt ether of 2,2-dimethylpropionic acid;
(1R*,2R*,4R*)-2-(2-{[3-(5,6-dichloro-1H-benzoimidazol-2-yl)propyl]-methylamino}ethyl)-5-Panevezio[2.2.2]Oct-5-EN-2-silt ether isobutane acid;
(1R*,2R*,4R*)-2-(2-{[3-(5,6-dichloro-1H-benzoimidazol-2-yl)propyl]-methylamino}ethyl)-5-Panevezio[2.2.2]Oct-5-EN-2-silt EF the R cyclopropanecarbonyl acid;
(1R*,2R*,4R*)-2-(2-{[3-(5,6-dimethoxy-1H-benzoimidazol-2-yl)propyl]-methylamino}ethyl)-5-Panevezio[2.2.2]Oct-5-EN-2-silt ether isobutane acid;
(1R*,2R*,4R*)-2-(2-{[3-(5-methoxy-1H-benzoimidazol-2-yl)propyl]-methylamino}ethyl)-5-Panevezio[2.2.2]Oct-5-EN-2-silt ether isobutane acid;
(1R*,2R*,4R*)-2-(2-{[3-(1H-benzoimidazol-2-yl)propyl]methylamino}ethyl)-5-(3-methoxyphenyl)bicyclo[2.2.2]Oct-5-EN-2-silt ether isobutane acid;
(1R*,2R*,4R*)-2-(2-{[3-(7-methoxy-4-methyl-1H-benzoimidazol-2-yl)propyl]methylamino}ethyl)-5-Panevezio[2.2.2]Oct-5-EN-2-silt ether isobutane acid;
(1R*,2R*,4R*)-2-(2-{[3-(7-ethoxy-1H-benzoimidazol-2-yl)propyl]-methylamino}ethyl)-5-Panevezio[2.2.2]Oct-5-EN-2-silt ether isobutane acid;
(1R*,2R*,4R*)-2-(2-{[2-(7-methoxy-1H-benzoimidazol-2-yl)ethyl]-methylamino}ethyl)-5-Panevezio[2.2.2]Oct-5-EN-2-silt ether isobutane acid;
(1R*,2R*,4R*)-2-(2-{[3-(7-isopropoxy-1H-benzoimidazol-2-yl)propyl]-methylamino}ethyl)-5-Panevezio[2.2.2]Oct-5-EN-2-silt ether isobutane acid;
(1R*,2R*,4R*)-2-(2-{[3-(7-isobutyryloxy-1H-benzoimidazol-2-yl)propyl]methylamino}ethyl)-5-Panevezio[2.2.2]Oct-5-EN-2-silt ether isobutane acid;
(1R*,2R*,4R*)-2-(2-{[3-(7-hydroxy-1H-benzoimidazol-2-yl)propyl]-methylamino}ethyl)-5-Panevezio[2.2.2]Oct-5-EN-2-silt ether isobutane acid;
(1R*,5R*,6R*)-6-(2-{[3-(7-methoxy-1H-benzoimidazol-2-yl)propyl]-methylamino}ethyl)-8-Panevezio[3.2.2]non-8-ene-6-silt EF the R isobutane acid;
(1R*,5R*,6R*)-6-(2-{[3-(4-methoxy-1H-benzoimidazol-2-yl)propyl]-methylamino}ethyl)-8-Panevezio[3.2.2]non-8-ene-6-silt ester of 3,3,3-Cryptor-propionic acid;
(1R*,2R*,4R*)-2-(2-{[3-(4-methoxy-1-methyl-1H-benzoimidazol-2-yl)-propyl]methylamino}ethyl)-5-Panevezio[2.2.2]Oct-5-EN-2-silt ether isobutane acid;
(1R*,2R*,4R*)-2-(2-{[3-(1H-benzoimidazol-2-yl)propyl]methylamino}ethyl)-5-(2,6-dimetilfenil)bicyclo[2.2.2]Oct-5-EN-2-silt ether isobutane acid;
(1R*,2R*,4R*)-2-(2-{[3-(1H-benzoimidazol-2-yl)propyl]methylamino}-ethyl)-5-o-televizija[2.2.2]Oct-5-EN-2-silt ether isobutane acid;
(1S,2S,4S)-2-(2-{[3-(4-methoxy-1H-benzoimidazol-2-yl)propyl]-methylamino}ethyl)-5-Panevezio[2.2.2]Oct-5-EN-2-silt ether isobutane acid;
(1R,2R,4R)-2-(2-{[3-(4-methoxy-1H-benzoimidazol-2-yl)propyl]-methylamino}ethyl)-5-Panevezio[2.2.2]Oct-5-EN-2-silt ether isobutane acid;
(1R*,2R*,4R*)-2-(2-{[3-(4-acetylamino-1H-benzoimidazol-2-yl)propyl]-methylamino}ethyl)-5-Panevezio[2.2.2]Oct-5-EN-2-silt ether isobutane acid;
(1R*,2R*,4R*)-2-(2-{[3-(4-chloro-1H-benzoimidazol-2-yl)propyl]-methylamino}ethyl)-5-Panevezio[2.2.2]Oct-5-EN-2-silt ether isobutane acid;
(1R*,2R*,4R*)-2-(2-{[3-(7-chloro-4-methoxy-1H-benzoimidazol-2-yl)propyl]-methylamino}ethyl)-5-Panevezio[2.2.2]Oct-5-EN-2-silt ether isobutane acid;
(1R*,2R*,4R*)-2-(2-{[3-(4,6-dimethoxy-1H-benzoimidazol-2-yl)propyl]-methylamino}ethyl)-5-Panevezio[2.2.2]Oct-5-EN-2-silt EPE is isobutane acid;
(1R*,2R*,4R*)-2-(2-{[3-(1H-benzoimidazol-2-yl)propyl]methylamino}ethyl)-5-m-televizija[2.2.2]Oct-5-EN-2-silt ether isobutane acid;
(1S,2S,4S)-2-(2-{[3-(4,6-dimethoxy-1H-benzoimidazol-2-yl)propyl]-methylamino}ethyl)-5-Panevezio[2.2.2]Oct-5-EN-2-silt ether isobutane acid;
(1R*,2R*,4R*)-2-(2-{[3-(4,7-dimethoxy-1H-benzoimidazol-2-yl)propyl]-methylamino}ethyl)-5-Panevezio[2.2.2]Oct-5-EN-2-silt ether isobutane acid;
(1R*,2R*,4R*)-2-(2-{[3-(4,6-bis-trifluoromethyl-1H-benzoimidazol-2-yl)-propyl]methylamino}ethyl)-5-Panevezio[2.2.2]Oct-5-EN-2-silt ether isobutane acid;
(1R*,2R*,4R*)-2-[2-({3-[4-(2-methoxyethoxy)-1H-benzoimidazol-2-yl]-propyl}methylamino)ethyl]-5-Panevezio[2.2.2]Oct-5-EN-2-silt ether isobutane acid;
(1R*,2R*,4R*)-2-(2-{[3-(4,5-dimethoxy-7-methyl-1H-benzoimidazol-2-yl)-propyl]methylamino}ethyl)-5-Panevezio[2.2.2]Oct-5-EN-2-silt ether isobutane acid;
(1S,2S,4S)-2-(2-{[3-(4,5-dimethoxy-7-methyl-1H-benzoimidazol-2-yl)-propyl]methylamino}ethyl)-5-Panevezio[2.2.2]Oct-5-EN-2-silt ether isobutane acid;
(1R*,5R*,6R*)-6-(2-{[3-(7-methoxy-4-methyl-1H-benzoimidazol-2-yl)-propyl]methylamino}ethyl)-8-Panevezio[3.2.2]non-8-ene-6-silt ether isobutane acid;
(1R,2R,4R)-2-(2-{[3-(4,7-dimethoxy-1H-benzoimidazol-2-yl)propyl]-methylamino}ethyl)-5-Panevezio[2.2.2]Oct-5-EN-2-silt ether isobutane acid;
(1R*,2R*,4R*)-2-(2-{methyl-[3-(4-triptoreline-1H-benzoimidazol-2-yl)propyl]amino}ethyl)-5-FeNi is bicyclo[2.2.2]Oct-5-EN-2-silt ether isobutane acid;
(1R*,5R*,6R*)-6-(2-{[3-(4,7-dimethoxy-1H-benzoimidazol-2-yl)propyl]-methylamino}ethyl)-8-Panevezio[3.2.2]non-8-ene-6-silt ether isobutane acid;
(1R*,2R*,4R*)-2-(2-{[3-(1H-benzoimidazol-2-yl)propyl]methylamino}ethyl)-5-p-televizija[2.2.2]Oct-5-EN-2-silt ether isobutane acid;
(1S,2S,4S)-2-(2-{[3-(4,7-dimethoxy-1H-benzoimidazol-2-yl)propyl]-methylamino}ethyl)-5-Panevezio[2.2.2]Oct-5-EN-2-silt ether isobutane acid;
(5R)-(1R*,2R*,4R*)-2-(2-{[3-(1H-benzoimidazol-2-yl)propyl]methylamino}-ethyl)-5-Panevezio[2.2.2]Oct-2-silt ether isobutane acid;
(5S)-(1R*,2R*,4R*)-2-(2-{[3-(1H-benzoimidazol-2-yl)propyl]methylamino}-ethyl)-5-Panevezio[2.2.2]Oct-2-silt ether isobutane acid;
(1R*,2R*,4R*)-2-(2-{[3-(1H-benzoimidazol-2-yl)propyl]methylamino}ethyl)-bicyclo[2.2.2]Oct-5-EN-2-silt ether isobutane acid;
(1R*,2R*,4R*,5R*)-2-(2-{[3-(1H-benzoimidazol-2-yl)propyl]methylamino}-ethyl)-5-methoxy-5-Panevezio[2.2.2]Oct-2-silt ether isobutane acid;
(1R*,2S*,4R*,5R*)-2-(2-{[3-(1H-benzoimidazol-2-yl)propyl]methylamino}-ethyl)-5-methoxy-5-Panevezio[2.2.2]Oct-2-silt ether isobutane acid;
(1R*,2R*,4R*)-2-(2-{[3-(1H-benzoimidazol-2-yl)propyl]methylamino}ethyl)-5-(3-forfinal)bicyclo[2.2.2]Oct-5-EN-2-silt ether isobutane acid;
(1R*,2R*,4R*)-2-(2-{[3-(1H-benzoimidazol-2-yl)propyl]methylamino}ethyl)-5-(4-forfinal)bicyclo[2.2.2]Oct-5-EN-2-silt ether isobutane acid; and
(1R*,2R*,4R*)-2-(2-{[3-(1H-benzoimidazol-2-yl)propyl]is ethylamino}ethyl)-5-pyridin-3-yl-bicyclo[2.2.2]Oct-5-EN-2-silt ether isobutane acid;
or pharmaceutically acceptable salt of such compounds.

10. The compound of formula (I) according to claims 1-9, or its pharmaceutically acceptable salt for use as a medicinal product, which is a calcium channel blocker L/T type.

11. Pharmaceutical composition, which is a calcium channel blocker L/T-type, containing as active substance a compound of the formula (I) according to claims 1-9, or its pharmaceutically acceptable salt, and at least one therapeutically inert excipient.



 

Same patents:

FIELD: chemistry.

SUBSTANCE: invention relates to triazole compounds which are represented by specific chemical formulae and which can be used for preventing or treating diseases in which 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) participates, particularly dementia. It was found that the triazole derivative, in which one of 3rd and 5th positions of the triazole ring accommodates a (di)alkyl methyl or cycloalkyl, each substituted, -O-aryl or heterocyclic group, each of which can be substituted, or (lower alkylene)cycloalkyl, and the other position accommodates an aryl, heterocyclic or cycloalkyl group, each of which can be substituted, or a pharmaceutically acceptable salt thereof, has powerful inhibiting action on 11β-HSD1.

EFFECT: improved properties of the derivatives.

8 cl, 141 tbl, 89 ex

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of general formula (I) , where is a substituted 5-member heteroaryl ring selected from thienyl, thiazolyl, oxazolyl, pyrrolyl, imidazolyl or pyrazolyl, W is selected from a group comprising N and -C=; M is selected from a group comprising -C(O)N(R1)OR2, -CXCONR1R2 and -C(O)OR1, or M is -C1-C2alkyl-C(O)N(R1)OR2, wherein is , R1 and R2 are independently selected from a group comprising -H, C1-C3-alkyl, C6-aryl, and C1-C3-alkyl-C6-aryl; R is selected from a group comprising H, C1-C3alkyl, halogen, NR1R2, -OR1 and C6aryl; n is an integer from 0 to 1; L and Y are as indicated in the claim; and to compounds of formula (II) , where L2 is selected from a group comprising H, - C0-C3alkyl- C6aryl, -C0-C3alkyl-heteroaryl, where the heteroaryl is pyridyl; -C1-C6alkyl, Y and M are the same as for compounds of formula (I). The invention also relates to a pharmaceutical composition based on compounds (I) and (II), having inhibiting action on histone deacetylase (HDAC), a method of inhibiting and a method of treating a disease which is sensitive to the HDAC inhibitor.

EFFECT: compounds of formula I and II as histone deacetylase inhibitors.

18 cl, 18 dwg, 10 tbl, 19 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel phenylaminopyrimidine compounds of formula I, which are JAK kinase inhibitors. In particular, these compounds selectively act on JAK2 kinase. The compounds can be used to treat diseases such as immunological and inflammatory diseases; hyperproliferative diseases, myeloproliferative diseases; viral diseases; metabolic diseases; and vascular diseases. In the compound of formula I , Q and Z are independently selected from N and CR1; R1 is independently selected from hydrogen, halogen, R2, OR2, OH, R4, OR4, CN, CF3, (CH2)nN(R2)2, where n equals 1,2 or 3, NO2, R2R4, NR2SO2R3, COR4, NR2COR3, CO2H, CO2R2, NR2COR4, R2CN, R2OH, R2OR3 and OR5R4; or two substitutes R1 together with carbon atoms with which they are bonded form an unsaturated 5- or 6-member heterocyclic ring containing 1-4 N atoms; R2 is C1-4alkyl; R4 is R2, C2-4alkenyl or phenyl; R4 is NH2, NHR2, N(R1)2, substituted or unsubstituted morpholine, CH2morpholine, substituted or unsubstituted thiomorpholine, substituted or unsubstituted thiomorpholino-1-oxide, substituted or unsubstituted thiomorpholino-1,1-dioxide, substituted or unsubstituted piperazinyl, substituted or unsubstituted piperidinyl, substituted or unsubstituted pyridinyl, substituted or unsubstituted pyrrolidinyl, substituted or unsubstituted pyrrolyl, substituted or unsubstituted oxazolyl, substituted or unsubstituted imidazolyl, substituted or tetrahydrofuranyl unsubstituted and substituted or unsubstituted tetrahydropyranyl; R5 is C2-4alkylene; R6-R9 are independently selected from H, RXCN, halogen, substituted or unsubstituted C1-4alkyl, OR1, CO2R1, N(R1)2, NO2 and CON(R1)2, wherein at least one of R6-R9 is RXCN; the rest of the values of the radicals are given in the claim.

EFFECT: high efficiency of treatment.

29 cl, 7 dwg, 2 tbl, 93 ex

FIELD: chemistry.

SUBSTANCE: invention relates organic chemistry and specifically to novel pyridine amide derivatives of general formula I where n equals 1; R1 and R2 together denote a residue selected from a group consisting of -CH=N-NH- and -CH=CH-N=CH-, which is bonded in any desirable direction to the parent structure or R2 and R3 together denote a residue selected from a group consisting of -CH=N-NH-; -CR28=N-NH-; -S-C(=S)-NH-; -S-CR29=N-; -N=CR30-O-; -N=CH-NH-; -N=N-NH-; -O-CH2-O-; -CH2-CH2-CH2-NH, -O-CH2-CH2-O-; -N=CH-CH=N-; -CH=CH-CH=N-, which is bonded in any desirable direction to the parent structure, or R3 and R4 together denote a -CH=N-NH- residue, which is bonded in any desirable direction to the parent structure, or R4 and R5 together denote a -CH=N-NH- residue, which is bonded in any desirable direction to the parent structure, and the rest of the residues R1, R2, R3, R4 and R5, mutually independently, in each case denote H; where R28 denotes F; Cl; Br or I; R29 and R30, mutually independently, in each case denote -NH-C(=O)-R31; -NH2; -NH-S(=O)2-R32; -NH-C(=O)-O-R33; -S-R34; where R31, R32, R33 and R34, mutually independently, in each case denote a straight or branched, saturated, unsubstituted aliphatic C1-10 residue; R6 denotes H or denotes a straight or branched, saturated, unsubstituted aliphatic C1-10 residue; R7 denotes hydrogen or -OH; R denotes -CF3; or denotes an unsubstituted tert-butyl residue; T denotes C-R35 and U denotes C-R36, V denotes N and W denotes C-R38; where R35 and R36 denote H; where R38 denotes -NR40R41; -OR42 or -SR43; where R40, R41, R42 and R43, mutually independently, in each case denote a straight or branched, saturated, unsubstituted aliphatic C1-10 residue; or denote a saturated, unsubstituted 3-, 4-, 5-, 6-, 7-, 8- or 9-member cycloaliphatic residue, or where R40 and R41 in each case together with a nitrogen atom as a ring member which binds them together, form a saturated 6-member heterocycloaliphatic residue, optionally substituted with one R57 residue, where R57 denotes a straight or branched, saturated, unsubstituted aliphatic C1-10 residue; in each case in form of corresponding physiologically acceptable salts. The invention also relates to a method of producing a compound of formula I, a medicinal agent based on the compound of formula I and use of the compound of formula I.

EFFECT: obtaining novel amide derivatives of pyridine, useful in treating vanilloid receptor 1 mediated diseases.

25 cl, 1 tbl, 18 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to a compound of formula or a pharmaceutically acceptable salt thereof, wherein G1 is phenyl or pyridyl, each of which is optionally additionally substituted by one substitute presented by T; G2 is phenyl, 1,3-thiazolyl or 1,3-oxazolyl, wherein G2 is bound to G1 in the para position in relation to a place of attachment of G1 to group NH in formula (I), wherein G2 means phenyl, G3 is bound to G2 in the para position of G2 in relation to G1, and wherein provided G2 represents 1,3-thiazolyl or 1,3-oxazolyl, G2 is bound to G1 in the position of 5 G2 and G3 is bound to G2 in the position of 2 G2; T in each case is independently specified in a group containing C1-6alkyl and halogen; G3 is presented by formula or by formula ; W1 is -C(R3)(R4)-C(R3)(R4)-, and W2 represents N; or W3 represents O; W4 is -C(R3)(R4) -; each R3 and R4 is hydrogen; each R5 and R6 kis hydrogen; Rc and Rd together with a carbon atom whereto attached, are a 4-5-member cycloalkyl or monocyclic heterocycle of formula ; wherein one hydrogen atoms attached to the carbon atom of the cycloalkyl ring and monocyclic heterocycle is optionally substituted by a radical specified in a group -C(O)O(R8); W5 is -CH2- or -CH2-CH2-; W6 is O or N(RX), wherein Rx is hydrogen, C1-6alkyl or -C(O)O(Rz); RZ in each case is independently C1-6alkyl; R8 is hydrogen; L1 is O; and X is hydrogen, C1-6alkyl, or - (CRgRh)u-C(O)O(R10); or L1 is -CH2- and X is -C(O)OH; R10 is hydrogen; or Q is G4 or Y1-Y3; or Q is described for formula wherein Z is phenyl; G4 is benzothiazole or benzoxazole optionally additionally substituted by 1 or 2 substitutes specified in a group consisting of C1-6alkyl, halogen and -OR1; Y1 in each case is independently -C(O)-, -C(O)O- or -C(O)N(Rw)-, wherein the right side -C(O)O- and -C(O)N(Rw)- of the groups is attached to Y3 or (CRJRk)v, Y3 in each case is independently phenyl, benzyl, piperidinyl or bicyclo[4.2.0]octa-1,3,5-triene, wherein the phenyl and benzyl residues are optionally additionally substituted by 1 or 2 substitutes specified in a group consisting of halogen and haloC1-6alkyl; Rg and Rh in each case is independently hydrogen, or C1-6alkyl; R1 in each case is independently halogenC1-6alkyl; Rw is hydrogen; and u means 1.

EFFECT: compounds being the type 1 diacylglycerol O-acyltransferase (DGAT-1) enzyme inhibitors.

7 cl, 1 tbl, 61 ex

FIELD: chemistry.

SUBSTANCE: invention refers to organic chemistry, more specifically to a method for preparing N-(1,5,3-dithiazocynan-3-yl)amides of formula , wherein R=p-C5H4N (a), (CH3)3CO (b), o-CH3OC6H4 (c), which can find application as biologically active compounds, selective sorbents and precious metal extractants. Substance of the method consists in the reaction of N1,N1,N7,N7 - tetramethyl-2,5-dithiaheptane-1,7-diamine with hydrazides RC(O)NHNH2 in the presence of the catalyst samaric nitrate crystallohydrate Sm(NO3)3·6H2O at temperature 65-75°C for 20-26 h.

EFFECT: what is developed is a method for preparing new high-selectivity N-(1,5,3-dithiazocynan-3-yl)amides.

1 cl, 1 tbl, 1 ex

FIELD: chemistry.

SUBSTANCE: invention describes a compound of formula I , in which X1, X2, X3, X4 and X5 independently denote -CH- or N; or X3, X4 and X5 independently denote -CH- or N, and X1 and X2 independently denote C and are part of an additional 6-member aromatic ring; in which R1 denotes methyl or ethyl, or R1 denotes hydrogen; R2 denotes methyl, ethyl, propyl, tert-butoxy carbonylmethyl, allyl, difluoromethyl, ethylbenzene, methylbenzene, butenyl, hydroxyethyl, tolyl, pentenyl, methoxyethyl, butynyl, propynyl, methylcarbonyloxy, cyclopentyl, each of which can be substituted with one or more identical or different substitutes selected from R5; or R2 denotes hydrogen; R3 denotes alkyl, cycloalkyl, alkenyl, cycloalkenyl, alkynyl, halogenalkyl, hydroxyalkyl, heterocycloalkenyl, alkylaryl, arylalkyl, alkylalkoxycarbonyl, alkylcarbonyloxy or alkoxyalkyl, each of which can be substituted with one or more identical or different substitutes selected from R6; or R3 denotes hydrogen, -CH2-C(O)-heterocycloalkyl or -CH2-C(O)NR9-R12; R11 denotes one or more identical or different substitutes selected from hydrogen, halogen, cyano, amino, alkyl, methylthionyl, methylsulphonyl, amino, cyano or alkoxy; where R5, R6, R9, R12 are as indicated in claim 1, under the condition that R1, R2 and R3 cannot be methyl at the same time; under the condition that when R2 and R3 both denote hydrogen, R1 cannot be methyl or hydrogen; under the condition that when R1 denotes methyl or hydrogen, R2 denotes methyl and R3 denotes hydrogen when ring B cannot be phenyl; and pharmaceutically acceptable salts and N oxides thereof. The invention also describes a pharmaceutical composition for use in case of skin diseases, said composition containing a compound of formula I, and use of said compound in preparing a medicinal agent for preventing conditions associated with skin wounds.

EFFECT: novel compounds which can be useful in treating skin diseases are obtained and described.

19 cl, 304 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a compound of formula 1:

or pharmaceutically acceptable salts thereof, where values of Cy1; Cy2; L1; L2, R; R1; Rx and Ry and R2 are given in claim 1.

EFFECT: compounds are suitable for use as Raf protein kinase inhibitors.

36 cl, 6 tbl

FIELD: chemistry.

SUBSTANCE: invention relates to compounds, which represent (4,5-dihydrooxazol-2-yl)-(5,6,7,8-tetrahydroquinoxylan-5-yl)-amino and (4,5-dihydrooxazol-2-yl(-(5,6,7,8-tetrahydroquinolin-5-yl)-amino or their pharmaceutically acceptable salt. Said compounds are applied in methods of intraocular pressure reduction and treatment of pain in mammals who require it.

EFFECT: obtaining compounds, which are alpha-adrenergic agonists.

3 cl, 1 tbl

FIELD: medicine, pharmaceutics.

SUBSTANCE: there are described macrocyclic phenylcarbamates of formula (I), wherein A represents -C(=O)OR1 or -C(=O)-NH-SO2-R2, wherein R1 represents hydrogen or C1-C6alkyl; R2 represetns C3-7cycloalkyl, phenyl, thiazolyl or pyridyl each of which is optionally substituted by one or more substituted specified in C1-6alkyl, C1-6alkoxy, trifluoromethyl and halogen; X represents N or CH; E represents NR5; R5 represents hydrogen, C1-6alkyl, C1-6alkoxyC1-6alkyl or C3-7cycloalkyl; n is equal to 4 or 5; wherein a dash line -----, adjoining the fragment -(CH2)n-, represents a double bond; and wherein the dash line in a five-merous cycle including X, represents a single bond, and R7 represents hydrogen; R8 is such as specified in the patent claim, or N-oxide thereof, a pharmaceutically acceptable additive salt or a pharmaceutically acceptable solvate possessing antiviral activity, and used as HCV inhibitors; as well as pharmaceutical compositions containing the above compounds as an active ingredient.

EFFECT: preparing the pharmaceutically acceptable additive salt or pharmaceutically acceptable solvate possessing antiviral activity.

10 cl, 23 ex, 1 tbl

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of formula (I) and/or stereoisomeric forms thereof and/or mixtures of said forms in any ratio and/or a physiologically tolerant salt of the compound of formula , where: X denotes -C(O)- or -SO2-, U denotes an oxygen atom or -(C0-C4)alkylene, A denotes an oxygen atom, -C(O)-NH-, -NH-C(O)- or -(C0-C4)alkylene, V denotes: 1) -(C2-C9)alkylene, where alkylene is unsubstituted or mono-, di- or tri-substituted, independently of each other, by an -OH group, 2) -(C3-C9)alkenylene, D denotes -(C1-C2)alkylene, Y denotes: 1) a covalent bond, 2) -(C6-C14)arylene-, or 3) Het, where Het denotes pyridyl or imidazolyl, R1 denotes: 1) a hydrogen atom, 2) -(C1-C6)alkyl, R3 denotes: 1) -(C2-C6)alkylene-NH2, 2) -(C1-C4)alkylene-SO2-(C1-C4) alkylene-NH2 or 3) -(C0-C4) alkylene-Het, where Het denotes pyridyl or piperidyl, where Het is unsubstituted or substituted with -NH2, R6 denotes: 1) a hydrogen atom, 2) -(C1-C6) alkyl, where the alkyl is unsubstituted or substituted, independently of each other, by a R16 group, 3) -(C0-C4) alkylene-Het, where Het denotes pyridyl, where -(C0-C4) alkylene and Het are unsubstituted or substituted, independently of each other, by a R16 group, 4) -(C0-C4) alkylene-phenyl, where -(C0-C4) alkylene and phenyl are unsubstituted or substituted, independently of each other, by a R16 group, or 5) -(C0-C4) alkylene-(C3-C8)cycloalkyl, R7 denotes a hydrogen atom, halogen or -(C1-C6)alkyl, R8 denotes a hydrogen atom or -(C1-C6)alkyl, R9 denotes a hydrogen atom, and R16 denotes -NH2, which are inhibitors of the active thrombin-activated fibrinolysis inhibitor, as well as a method for production thereof, a medicinal agent based thereon and use for prevention, secondary prevention and treatment of one or more disorders associated with thrombosis, embolism, hypercoagulation or fibrosis changes.

EFFECT: improved properties of compounds.

7 cl, 1 tbl, 9 ex

FIELD: chemistry.

SUBSTANCE: starting substances used are thiosemicarbazide, acetic anhydride, sodium hydroxide, monochloroacetic acid; the liquid medium used is 95% ethanol and purified water, wherein the thiosemicarbazide is dissolved in the purified water, the reaction mass is cooled to 0°C±0.5°C and while mixing, acetic anhydride is added at such a rate that temperature of the reaction mass does not rise above 4°C; after adding all the acetic anhydride, the mass is mixed for another 20-30 minutes at temperature not higher than 1°C±1°C; the precipitate is filtered, washed with cooled water (2-4°C), pressed and the purified water and the obtained moist precipitate are then placed in a round-bottom flask with a mixer; while stirring for 0.5-1 hours, sodium hydroxide solution is added to the reaction mass and then boiled for 1 hour; the monochloroacetic acid is then added to water, stirred for 30 minutes and boiled for 1 hour, cooled to 2-4°C; the precipitate is filtered, washed with cold water thrice and twice with cold 95% ethanol; the obtained moist precipitate is transferred into the round-bottom flask with a mixer; 95% ethanol is added, stirred and while stirring, morpholine solution is added to 95% ethanol, boiled while stirring for 30 minutes and then cooled to 85-90°; activated carbon is added, boiled for 10-20 minutes; the carbon is filtered, the filtrate is cooled to 4-5°C, the precipitate of the end product is filtered, washed with 95% ethanol and dried at 50-70°C.

EFFECT: high output of the end product, high quality of said product, cheap production and faster process.

1 cl, 1 ex

FIELD: chemistry.

SUBSTANCE: invention relates to triazole compounds which are represented by specific chemical formulae and which can be used for preventing or treating diseases in which 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) participates, particularly dementia. It was found that the triazole derivative, in which one of 3rd and 5th positions of the triazole ring accommodates a (di)alkyl methyl or cycloalkyl, each substituted, -O-aryl or heterocyclic group, each of which can be substituted, or (lower alkylene)cycloalkyl, and the other position accommodates an aryl, heterocyclic or cycloalkyl group, each of which can be substituted, or a pharmaceutically acceptable salt thereof, has powerful inhibiting action on 11β-HSD1.

EFFECT: improved properties of the derivatives.

8 cl, 141 tbl, 89 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel phenylaminopyrimidine compounds of formula I, which are JAK kinase inhibitors. In particular, these compounds selectively act on JAK2 kinase. The compounds can be used to treat diseases such as immunological and inflammatory diseases; hyperproliferative diseases, myeloproliferative diseases; viral diseases; metabolic diseases; and vascular diseases. In the compound of formula I , Q and Z are independently selected from N and CR1; R1 is independently selected from hydrogen, halogen, R2, OR2, OH, R4, OR4, CN, CF3, (CH2)nN(R2)2, where n equals 1,2 or 3, NO2, R2R4, NR2SO2R3, COR4, NR2COR3, CO2H, CO2R2, NR2COR4, R2CN, R2OH, R2OR3 and OR5R4; or two substitutes R1 together with carbon atoms with which they are bonded form an unsaturated 5- or 6-member heterocyclic ring containing 1-4 N atoms; R2 is C1-4alkyl; R4 is R2, C2-4alkenyl or phenyl; R4 is NH2, NHR2, N(R1)2, substituted or unsubstituted morpholine, CH2morpholine, substituted or unsubstituted thiomorpholine, substituted or unsubstituted thiomorpholino-1-oxide, substituted or unsubstituted thiomorpholino-1,1-dioxide, substituted or unsubstituted piperazinyl, substituted or unsubstituted piperidinyl, substituted or unsubstituted pyridinyl, substituted or unsubstituted pyrrolidinyl, substituted or unsubstituted pyrrolyl, substituted or unsubstituted oxazolyl, substituted or unsubstituted imidazolyl, substituted or tetrahydrofuranyl unsubstituted and substituted or unsubstituted tetrahydropyranyl; R5 is C2-4alkylene; R6-R9 are independently selected from H, RXCN, halogen, substituted or unsubstituted C1-4alkyl, OR1, CO2R1, N(R1)2, NO2 and CON(R1)2, wherein at least one of R6-R9 is RXCN; the rest of the values of the radicals are given in the claim.

EFFECT: high efficiency of treatment.

29 cl, 7 dwg, 2 tbl, 93 ex

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of general formula (1) or salts thereof, where in formula (1) R1 is a lower C1-C6alkyl group, a lower C3-C6cycloalkyl group, a phenyl group, a heterocyclic group, which relates to a residue formed by removing a hydrogen atom from a saturated or unsaturated monocyclic heterocyclic ring containing one, two or three heteroatoms in the ring, selected from a nitrogen atom, an oxygen atom and a sulphur atom, or a phenyl(C1-C6alkyl) group; in cases when R1 is a lower C1-C6alkyl group, that lower C1-C6alkyl group can have, as substitute(s), one, two or three groups selected from a halogen atom, a heterocyclic group which relates to a residue formed by removing a hydrogen atom from a saturated monocyclic heterocyclic ring containing one or two heteroatoms in the ring, selected from a nitrogen atom and an oxygen atom, a carboxyl group, a lower C1-C6alkoxycarbonyl group, a lower C1-C6alkylamino group, a lower C1-C6alkylamino group, substituted with a lower C1-C6alkylamino group, a lower C1-C6alkylamino group, substituted with a phenyl group; in cases when R1 is a phenyl group, a heterocyclic group which relates to a residue formed by removing a hydrogen atom from a saturated or unsaturated monocyclic heterocyclic ring containing one, two or three heteroatoms in the ring, selected from a nitrogen atom, an oxygen atom or a sulphur atom, or a phenyl(C1-C6alkyl) group, that phenyl, heterocyclic or phenyl(C1-C6alkyl) group can contain, as substitute(s), one, two or three groups selected from a halogen atom, a lower C1-C6alkyl group, a hydroxyl group or a lower C1-C6alkoxy group; R2 is a hydrogen atom or a lower C1-C6alkyl group; R3 is a hydrogen atom or a lower C1-C6alkyl group; R4 and R5 can be identical or different and are a hydrogen atom or a lower C1-C6alkyl group; R6 is a hydrogen atom or a lower C1-C6alkyl group; R7 is a phenyl group or a heterocyclic group which relates to a residue formed by removing a hydrogen atom from a saturated monocyclic heterocyclic ring containing one heteroatom in the ring, selected from an oxygen atom and a sulphur atom; in cases where R7 is a phenyl group or a heterocyclic group which relates to a residue formed by removing a hydrogen atom from a saturated monocyclic heterocyclic ring containing one heteroatom in the ring, selected from an oxygen atom and a sulphur atom, that phenyl or heterocyclic group can contain, as substitute(s), one or two groups selected from a halogen atom, a lower C1-C6alkyl group, a hydroxyl group, a lower C1-C6alkoxy group and a nitro group; W is an oxygen atom or NR8; R8 is a hydrogen atom or a lower C1-C6alkyl group; X is an oxygen atom or a sulphur atom; Y is a lower C1-C6alkylene group; Z is an oxygen atom, a sulphur atom, NR9 or OCO; R9 is a hydrogen atom or a lower C1-C6alkyl group. The invention also relates to a pharmaceutical composition based on said compounds, having GR binding activity.

EFFECT: obtaining novel compounds and a pharmaceutical composition based on said compounds, which can be used in medicine as glucocorticoid receptor modulators.

10 cl, 1 tbl, 3 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel heterocyclic nitrogen- and oxygen-containing compounds having insecticidal activity. In formulae (A) (B) (C) (D) R1 is a 5- or 6-member heterocyclic ring containing a nitrogen, oxygen and/ or sulphur atom, a halogen-substituted 5- or 6-member heterocyclic ring containing a nitrogen, oxygen and/or sulphur atom, a substituted or unsubstituted phenyl, where the substitutes are one or more groups selected from a group consisting of halogen atoms, C1-4 halogen alkyl or C1-4 chloroalkoxyl; R5, R6, R7, R8 and R9 are H, saturated or unsaturated C1-4 alkyl, halogen atom, saturated or unsaturated C1-4 alkoxyl, saturated C1-4 halogenalkoxyl, C1-4 alkylcarbonyl, C1-8 alkyl ester, C1-4 alkylsulphonyl, phenyl, benzyl or trifluoromethane sulphonyl ether group; Y is nitro, cyano, trifluoromethyl, trifluoroacetyl or trifluoromethylsuphonyl. Values of radicals R, R2-R4 are given in the claim.

EFFECT: invention also relates to an agrochemical composition containing said compounds, use of the agrochemical composition in pest control and a method of producing said compounds.

12 cl, 7 tbl, 36 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel of 2,4-pyrimidine diamine compounds of formula I, which inhibit degranulation of immune cells and can be used in treating cell reactions mediated by FcεRI or FcγRl receptors. In formula (I) each R2 and R4 is independently phenyl substituted with one or more R8 groups or a heteroaryl selected from a group consisting of , where the heteroaryl is optionally substituted with one or more R8 groups and at least one of R2 and R4 is a heteroaryl; R5 is selected from a group consisting of (C1-C6)alkyl, optionally substituted with one or more identical or different R8 groups, -ORd, -SRd, fluorine, (C1-C3)halogenalkyloxy, (C1-C3)perhalogenalkyloxy, -NRcRc, (C1-C3)halogenalkyl, -CN, -NO2, -C(O)Rd, -C(O)ORd, -C(O)NRcRc, -C(NH)NRcRc, -OC(O)Rd, -OC(O)ORd, -OC(O)NRcRc; -OC(NH)NRcRc, - [NHC(O)]nORd, R35 is hydrogen or R8; each Y is independently selected from a group consisting of O, S and NH; each Y1 is independently selected from a group consisting of O, S and NH; each Y2 is independently selected from a group consisting of CH, CH2, S, N, NH and NR37. Other values of radicals are given in the claim.

EFFECT: improved efficiency.

19 cl, 6 tbl.

FIELD: chemistry.

SUBSTANCE: invention describes a compound of formula I , in which X1, X2, X3, X4 and X5 independently denote -CH- or N; or X3, X4 and X5 independently denote -CH- or N, and X1 and X2 independently denote C and are part of an additional 6-member aromatic ring; in which R1 denotes methyl or ethyl, or R1 denotes hydrogen; R2 denotes methyl, ethyl, propyl, tert-butoxy carbonylmethyl, allyl, difluoromethyl, ethylbenzene, methylbenzene, butenyl, hydroxyethyl, tolyl, pentenyl, methoxyethyl, butynyl, propynyl, methylcarbonyloxy, cyclopentyl, each of which can be substituted with one or more identical or different substitutes selected from R5; or R2 denotes hydrogen; R3 denotes alkyl, cycloalkyl, alkenyl, cycloalkenyl, alkynyl, halogenalkyl, hydroxyalkyl, heterocycloalkenyl, alkylaryl, arylalkyl, alkylalkoxycarbonyl, alkylcarbonyloxy or alkoxyalkyl, each of which can be substituted with one or more identical or different substitutes selected from R6; or R3 denotes hydrogen, -CH2-C(O)-heterocycloalkyl or -CH2-C(O)NR9-R12; R11 denotes one or more identical or different substitutes selected from hydrogen, halogen, cyano, amino, alkyl, methylthionyl, methylsulphonyl, amino, cyano or alkoxy; where R5, R6, R9, R12 are as indicated in claim 1, under the condition that R1, R2 and R3 cannot be methyl at the same time; under the condition that when R2 and R3 both denote hydrogen, R1 cannot be methyl or hydrogen; under the condition that when R1 denotes methyl or hydrogen, R2 denotes methyl and R3 denotes hydrogen when ring B cannot be phenyl; and pharmaceutically acceptable salts and N oxides thereof. The invention also describes a pharmaceutical composition for use in case of skin diseases, said composition containing a compound of formula I, and use of said compound in preparing a medicinal agent for preventing conditions associated with skin wounds.

EFFECT: novel compounds which can be useful in treating skin diseases are obtained and described.

19 cl, 304 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: described are novel aminitriazole derivatives of formula (I), where A is phenyl, heterocyclyl or propan-1,3-diyl; E is *-C1-4alkyl-O-, -CH=CH- or , where asterisks stand for bond, through which binding with R1; Q- O or S occurs; R3 is hydrogen, C1-4alkyl, cyclopropyl, C1-4alkoxy-C1-4alkyl, benzyl or -CH2CH2C(O)O-tert-Bu; R1 is pyridyl or phenyl, possibly substituted with halogen, C1-4alkyl, C1-4alkoxy, C1-4fluoroalkyl, C1-4fluoroalkoxy, di-( C1-3alkyl)amino or C1-4alkoxy-C1-2alkyl; and R2 is -CO-C1-3alkyl,-CF2-C1-3alkyl or -SO2-C1-3alkyl; or their pharmaceutically acceptable salts, pharmaceutical composition, which contains them.

EFFECT: obtaining novel compounds for treatment of inflammatory disease or Alzheimer's disease.

20 cl, 105 ex, 1 tbl

FIELD: chemistry.

SUBSTANCE: invention relates to compounds, which represent (4,5-dihydrooxazol-2-yl)-(5,6,7,8-tetrahydroquinoxylan-5-yl)-amino and (4,5-dihydrooxazol-2-yl(-(5,6,7,8-tetrahydroquinolin-5-yl)-amino or their pharmaceutically acceptable salt. Said compounds are applied in methods of intraocular pressure reduction and treatment of pain in mammals who require it.

EFFECT: obtaining compounds, which are alpha-adrenergic agonists.

3 cl, 1 tbl

FIELD: chemistry.

SUBSTANCE: invention relates to sulphonamide compounds of formula or pharmaceutically acceptable salts thereof, wherein A is phenyl, optionally substituted with 1 or 2 halogen atoms, C1-6 alkyl group, trifluoromethyl group, C1-6 alkoxy group or -SCH3 group, thiophenyl, optionally substituted with a C1-C6 alkyl group or a halogen atom, pyridinyl, optionally substituted with a halogen atom, naphthalenyl or dihydroindenyl; R1 denotes the following formulae or [in formulae (R1a) and (R1b) Ar1 denotes the following formulae , or (each R5 and R6 independently denotes a hydrogen atom, a halogen atom, a C1-6 alkyl group optionally substituted with up to three halogen atoms, C1-6 lower alkoxy group optionally substituted with up to three halogen atoms); Ar2 denotes the following formulae , or (each R7 and R8 independently denotes a hydrogen atom, a hydroxyl group, a halogen atom, a C1-6 alkyl group optionally substituted with up to three halogen atoms or a C1-6 lower alkoxy group optionally substituted with up to three halogen atoms, an amine group, a nitro group, a C2-6 acyl group, or R7 and R8 together form -CH2CH2O-; R9 is a hydrogen atom or - J-COOR10; J is a covalent bond, alkylene containing 1 to 5 carbon atoms, alkenylene containing 2 to 5 carbon atoms or alkynylene containing 2 to 5 carbon atoms, where one carbon atom in said alkylene groups can be substituted with an oxygen atom, a sulphur atom, NR11, CONR11 or NR11CO in any chemically acceptable position; R11 is a hydrogen atom; and R10 is a hydrogen atom); and p equals 0 or 1]; R2 is a C1-6 alkyl group; each R3 and R4 is independently a C1-6 alkyl group; * denotes an asymmetric carbon atom; and m equals an integer from 1 to 3. The invention also relates to a medicinal agent for stimulating PTH secretion.

EFFECT: obtaining novel compounds which can be used in medicine to prevent or treat primary or secondary osteoporosis.

29 cl, 15 tbl, 14 ex

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