Trpv1 antagonists and use thereof

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of formula 1 or pharmaceutically acceptable derivatives thereof, where values of radicals X, W, R4, Ar1, Ar2, R3, R4, R20 are as described in paragraph 1 of the claim. The invention also describes a composition for treating or preventing pain, UI, ulcers, inflammatory bowel disease or irritable bowel syndrome.

EFFECT: compound which can be used in medicine is obtained and described.

46 cl, 10 ex, 1 tbl

 

The text descriptions are given in facsimile form.

1. The compound of formula I:

or its pharmaceutically acceptable derivatives, where X represents O, S, N-CN, N-OH or N-OR10;
W represents N or C;
the dotted line means the presence or the absence of communication, and when the dotted line means the presence of a relationship or W represents N, then R4no, otherwise, R4represents-H, -OH, -OCF3, -halogen, -(C1-C6)alkyl, -CH2OH, -CH2Cl, -CH2Br, -CH2I, -CH2F, -CH(halogen)2, -CF3, -OR10, -SR10, -COOH, -COOR10, -C(O)R10-C(O)H, -OC(O)R10, -OC(O)other10, -NHC(O)R13, -CON(R13)2, -S(O)2R10or NO2;
R10represents -(C1-C4)alkyl;
each R13independently represents-H, -(C1-C4)alkyl, -(C1-C4)alkenyl, -(C1-C4)quinil or-phenyl;
Ar1represents a
,, ,,
,,,
,or;
Ar2represents a
,,,
,
,,,or;
since is an integer of 0, 1 or 2;
Y1, Y2, Y3independently represent C, N or O;
where not more than one of Y1, Y2or Y3can be About and for each Y1, Y2and Y3, which is N, N is associated with one RZ1group and for each Y1, Y2and Y3that is, associated with two R10groups, provided that there are not more than the total number consisting of two (C1-C6)alkyl groups substituted on all of Y1, Y2and Y3;
R12aand R12bindependently represent-H or -(C1-C6)alkyl;
E represents =O,=S,=CH(C1-C5)alkyl, =CH(C1-C5)alkenyl, -NH(C1-C6)al the Il or =N-OR 20;
R1represents-H, -halogen, -(C1-C4)alkyl, -NO2, -CN, -OH, -och3, -NH2-C(halogen)2, -CH(halogen)2, -CH2(halogen), -OC(halogen)3, -Och(halo)2or-OCH2(halogen);
each R2independently represents:
(a) -halogen, -OH, -O(C1-C4)alkyl, -CN, -NO2, -NH2-(C1-C10)alkyl, -(C2-C10)alkenyl -(C2-C10)quinil, -phenyl, or
(b) a group of formula Q;
where Q is a
,,,,,
,,,,
,or;
Z1represents-H, -OR7, -SR7, -CH2-OR7, -CH2-SR7, -CH2-N(R20)2or-halogen;
Z2represents-H, -(C1-C6)alkyl, -(C2-C6)alkenyl -(C2-C6)quinil, -CH2-OR7, -phenyl or-halogen;
each Z3independently represents-H, -(C1-C6)alkyl, -(C2-C6)alkenyl -(C2-C6)quinil or-phenyl;
Z4represents H, -OH, -OR10, -(C1-C6)alkyl or-N(R20)2;
J represents-OR20, -SR20, -N(R20)2or-CN;
provided that at least one R2the group represents a group of formula Q, and provided that when Z1represents-OR7or-SR7then Z2is-halogen;
each R3independently represents:
(a) -H, (C1-C6)alkyl, or CH2OR7; or
(b) two R3groups together form a (C2-C6)bridge, which is unsubstituted or substituted with 1, 2 or 3 independently selected R8groups and the specified bridge optionally contains a group-HC=CH - within the (C2-C6)bridge; or
(c) two R3groups together form-CH2-N(Ra)-CH2- bridge,

Raselected from-H, -(C1-C6)alkyl, -(C3-C8)cycloalkyl, -CH2-C(O)-Rc, -(CH2)-C(O)-ORc, -(CH2)-C(O)-N(Rc)2, -(CH2)2-O-Rc, -(CH2)2-S(O)2-N(Rc)2or -(CH2)2-N(Rc)S(O)2-Rc;
Rbchoose from:
(a) -H, -(C1-C6)alkyl, -(C3-C8)cycloalkyl, -(3 - to 7-membered)heterocycle, -N(Rc)2, -N(Rc)-(C3-C8)cycloalkyl or-N(Rc)(from 3-to 7-membered)heterocycle; or
(b) -phenyl, -(5 - or 6-membered)heteroaryl, -N(Rc)-phenyl, or-N(Rc)-(5 - to 10-membered)heteroaryl, each of which is unsubstituted or substituted with 1, 2 or 3 independently selected R7groups;
each Rcindependently selected from-H or -(C1-C4)alkyl;
each R7independently represents-H, -(C1-C6)alkyl, -(C1-C6)alkenyl -(C2-C6)quinil, -(C3-C8)cycloalkyl, -(C5-C8)cycloalkenyl, -phenyl, -(C1-C6)halogenated, -(C1-C6)hydroxyalkyl, -(C1-C6)alkoxy(C1-C6)alkyl, -(C1-C6)alkyl-N(R20)2or-CON(R20)2;
each R8and R9independently represents:
(a) -(C1-C6)alkyl, -(C2-C6)alkenyl -(C2-C6)quinil -(C3-C8)cycloalkyl, -(C5-C8)cycloalkenyl or-phenyl, each of which is unsubstituted or substituted with 1 or 2-Oh groups; or
(b) -H, -CH2C(halogen)3-C(halogen)3, -CH(halogen)2, -CH2(halogen), -OC(halogen)3, -Och(halo)2, -OCH2(halogen), -SC(halogen)3, -SCH(halogen)2, -SCH2(halogen), -CN, -O-CN, -OH, -halogen, -N3, -NO2, -CH=NR7, -N(R7)2, -NR7OH, -OR7, -C(O)R7 , -C(O)OR7, -OC(O)R7, -OC(O)OR7, -SR7, -S(O)R7or-S(O)2R7;
each R11independently represents-CN, -OH, -(C1-C6)alkyl, -(C2-C6)alkenyl, -halogen, -N3, -NO2, -N(R7)2, -CH=NR7, -NR7OH, -OR7, -C(O)R7, -OC(O)R7or-OC(O)OR7;
each R14independently represents-H, -(C1-C6)alkyl, -(C2-C6)alkenyl -(C2-C6)quinil -(C3-C8)cycloalkyl, -(C5-C8)cycloalkenyl, -(C1-C6)alkoxy-(C1-C6)alkyl, -phenyl, -C(halogen)3, -CH(halogen)2, -CH2(halogen), -(3 - to 7-membered)heterocycle, -(C1-C6)halogenated -(C2-C6)halogenoalkanes -(C2-C6)halogenoalkanes -(C2-C6)hydroxyalkyl -(C2-C6)hydroxyalkyl, -(C1-C6)alkoxy(C2-C6)alkyl, -(C1-C6)alkoxy(C2-C6)alkenyl, -(C1-C6)alkoxy(C2-C6)quinil, -(C1-C6)alkoxy(C3-C8)cycloalkyl, -CN, -OH, -halogen, -OC(halogen)3, -N3, -NO2, -CH=NR7, -N(R7)2, -NR7OH, -OR7, -SR7, -O(CH2)bOR7, -O(CH2)bSR7, -O(CH2)bN(R7)2, -N(R7)(CH2)bOR7-N(R 7)(CH2)bSR7, -N(R7)(CH2)bN(R7)2, -N(R7)COR7, -C(O)R7, -C(O)OR7, -OC(O)R7, -OC(O)OR7, -S(O)R7or-S(O)2R7, -S(O)2N(R7)2, -SO2C(halogen)3, -SO2(from 3 - to 7-membered)heterocycle, -CON(R7)2, -(C1-C5)alkyl-C=NOR7, -(C1-C5)alkyl-C(O)-N(R7)2, -(C1-C6)alkyl-NHSO2N(R7)2or -(C1-C6)alkyl-C(=NH)-N(R7)2;
each R20independently represents-H, -(C1-C6)alkyl or -(C3-C8)cycloalkyl;
each R21independently represents-H, -(C1-C6)alkyl,
,,
or;
each halogen independently represents-F, -Cl, -Br or-I;
n is an integer equal to 1, 2 or 3;
p is an integer equal to 1 or 2;
each b independently represents 1 or 2;
q represents an integer of 0, 1, 2, 3 or 4;
r is an integer equal to 0, 1, 2, 3, 4, 5 or 6;
s represents an integer of 0, 1, 2, 3, 4 or 5;
t represents an integer of 0, 1, 2 or 3; and m represents an integer of 0, 1 or 2.

2. The compound of formula I:

or its pharmaceutically acceptable derivative, where
X represents O, S, N-CN, N-OH or N-OR10;
W represents N or C;
the dotted line means the presence or the absence of communication, and when the dotted line means the presence of a relationship or W represents N, then R4no, otherwise, R4represents-H, -OH, -OCF3, -halogen, -(C1-C6)alkyl, -CH2OH, -CH2Cl, -CH2Br, -CH2I, -CH2F, -CH(halogen)2, -CF3, -OR10, -SR10, -COOH, -COOR10, -C(O)R10-C(O)H, -OC(O)R10, -OC(O)other10,-NHC(O)R13,-CON(R13)2,-S(O)2R10or NO2;
R10represents -(C1-C4)alkyl;
each R13independently represents-H, -(C1-C4)alkyl, -(C1-C4)alkenyl, -(C1-C4)quinil or-phenyl;
Ar1represents a
,,,,
,or;
Ar2represents a
,,,
,
,,,or;
since is an integer of 0, 1 or 2;
Y1, Y2, Y3independently represent C or N;
where for each Y1, Y1and Y3, which is N, N is associated with one R10group and for each Y1, Y2and Y3that is, associated with two R20groups, provided that there are not more than the total number consisting of two (C1-C6)alkyl groups, substituted for Y1, Y2and Y3;
R12aand R12bindependently represent-H or -(C1-C6)alkyl;
E represents =O, =S, =CH(C1-C5)alkyl, =CH(C1-C5)alkenyl, -NH(C1-C6)alkyl or =N-OR20;
R1represents-H, -halogen, -(C1-C4)alkyl, -NO2, -CN, -OH, -och3, -NH2-C(halogen)3, -CH(halogen)2, -CH2(halogen), -OC(halogen)3, -Och(halo)2or-OCH2(halogen);
each R2independently represents:
(a) -halogen, -OH, -O(C1-C4)alkyl, -CN, -NO2, -NH2-(C1-C10)alkyl, -(C2-C10)alkenyl -(C2-C10)quinil, -phenyl, or
(b) a group of formula Q
where Q is a
;
Z1represents-OH, -SH, -N(R20)2, -CH2-OH, -CH2-SH or-CH2-N(R20)2;
Z2represents-H, -CH3or CH2OR7and every Z3independently represents-H or-CH3;
J represents-OH, -SH, or-N(R20)2;
provided that at least one R2the group represents a group of formula Q;
each R3independently represents:
(a) N or (C1-C6)alkyl; or
(b) two R3groups together form a (C2-C6)bridge, which is unsubstituted or substituted with 1, 2 or 3 independently selected R8groups and the specified bridge optionally contains a group-HC=CH - within the (C2-C6)bridge; or
(c) two R3groups together form-CH2-N(Ra)-CH2- bridge,

Raselected from-H, -(C1-C6)alkyl, -(C3-C8)cycloalkyl, -CH2-C(O)-Rc, -(CH2)-C(O)-ORc, -(CH2)-C(O)-N(Rc)2, -(CH2)2-O-Rc, -(CH2)2-S(O)2-N(Rc)2or -(CH2)2-N(Rc)S(O)2-Rc;
Rbchoose from:
(a) -H, -(C1-C6)alkyl, -(C3-C8)cycloalkyl, -(3 - to 7-clinohumite, -N(Rc)2, -N(Rc)-(C3-C8)cycloalkyl or-N(Rc)-(3-to 7-membered)heterocycle; or
(b) -phenyl, -(5 - or 6-membered)heteroaryl, -N(Rc)-phenyl, or-N(Rc)-(5 - to 10-membered)heteroaryl, each of which is unsubstituted or substituted with 1, 2 or 3 independently selected R7groups;
each Rcindependently selected from-H or -(C1-C4)alkyl;
each R7independently represents-H, -(C1-C6)alkyl, -(C2-C6)alkenyl -(C2-C6)quinil, -(C3-C8)cycloalkyl, -(C5-C8)cycloalkenyl, -phenyl, -(C1-C6)halogenated, -(C1-C6)hydroxyalkyl, -(C1-C6)alkoxy(C1-C6)alkyl, -(C1-C6)alkyl-N(R20)2or CON(R20)2;
each R8and R9independently represents:
(a) -(C1-C6)alkyl, -(C2-C6)alkenyl -(C2-C6)quinil -(C3-C8)cycloalkyl, -(C5-C8)cycloalkenyl or-phenyl, each of which is unsubstituted or substituted with 1 or 2-Oh groups; or
(b) -H, -CH2C(halogen)3-C(halogen)3, -CH(halogen)2, -CH2(halogen), -OC(halogen)3, -Och(halo)2, -OCH2(halogen), -SC(halogen)3, -SCH(halogen)2, -SCH2(Gal the gene), -CN, -O-CN, -OH, -halogen, -N3, -NO2, -CH=NR7, -N(R7)2, -NR7OH, -OR7, -C(O)R7, -C(O)OR7, -OC(O)R7, -OC(O)OR7, -SR7, -S(O)R7or-S(O)2R7;
each R11independently represents-CN, -OH, -(C1-C6)alkyl, -(C2-C6)alkenyl, -halogen, -N3, -NO2, -N(R7)2, -CH=NR7, -NR7OH, -OR7, -C(O)R7, -OC(O)R7or-OC(O)OR7;
each R14independently represents-H, -(C1-C6)alkyl, -(C2-C6)alkenyl -(C2-C6)quinil, -(C3-C8)cycloalkyl -(C5-C8)cycloalkenyl, -(C1-C6)alkoxy-(C1-C6)alkyl, -phenyl, -C(halogen)3, -CH(halogen)2, -CH2(halogen), -(3 - to 7-membered)heterocycle, -(C1-C6)halogenated -(C2-C6)halogenoalkanes -(C2-C6)halogenoalkanes -(C2-C6)hydroxyalkyl -(C2-C6)hydroxyalkyl, -(C1-C6)alkoxy(C2-C6)alkyl, -(C1-C6)alkoxy(C2-C6)alkenyl, -(C1-C6)alkoxy(C2-C6)quinil, -(C1-C6)alkoxy(C3-C8)cycloalkyl, -CN, -OH, -halogen, -OC(halogen)3, -N3, -NO2, -CH=NR7, -N(R7)2, -NR7OH, -OR7, -SR7, -O(CH2)bOR7,-O(CH 2)bSR7, -O(CH2)bN(R7)2, -N(R7)(CH2)bOR7, -N(R7)(CH2)bSR7, -N(R7)(CH2)bN(R7)2, -N(R7)COR7, -C(O)R7, -C(O)OR7, -OC(O)R7, -OC(O)OR7, -S(O)R7or-S(O)2R7, -S(O)2N(R7)2, -SO2C(halogen)3, -SO2(from 3 - to 7-membered)heterocycle, -CON(R7)2, -(C1-C5)alkyl-C=NOR7, -(C1-C5)alkyl-C(O)-N(R7)2, -(C1-C6)alkyl-NHSO2N(R7)2or -(C1-C6)alkyl-C(=NH)-H(R7)2;
each R20independently represents-H, -(C1-C6)alkyl or -(C3-C8)cycloalkyl;
each halogen independently represents-F, -Cl, -Br or-I;
n is an integer equal to 1, 2 or 3;
p is an integer equal to 1 or 2;
each b independently represents 1 or 2;
q represents an integer of 0, 1, 2, 3 or 4;
r is an integer equal to 0, 1, 2, 3, 4, 5 or 6;
s represents an integer of 0, 1, 2, 3, 4 or 5;
t represents an integer of 0, 1, 2 or 3; and m represents an integer of 0, 1 or 2.

3. The compound of formula III:

or its pharmaceutically acceptable salt, where
X is the Wallpaper On, S, N-CN, N-OH or N-OR10;
W represents N or C;
the dotted line means the presence or absence of a relationship and when the dotted line means the presence of communication or W represents N, then R4no, otherwise, R4represents-H, -OH, -OCF3, -halogen, -(C1-C6)alkyl, -CH2OH, -CH2Cl, -CH2Br, -CH2I, -CH2F, -CH(halogen)2, -CF3, -OR10, -SR10, -COOH, -COOR10, -C(O)R10-C(O)H, -OC(O)R10, -OC(O)other10, -NHC(O)R13, -CON(R13)2, -S(O)2R10or NO2;
each R3independently represents:
(a) N or (C1-C6)alkyl; or
(b) two R3groups together form a (C2-C6)bridge, which is unsubstituted or substituted with 1, 2 or 3 independently selected R8groups and the specified bridge optionally contains a group-HC=CH - within the (C2-C6)bridge; or
(c) two R3groups together form-CH2-N(Ra)-CH2- bridge,

Raselected from-H, -(C1-C6)alkyl, -(C3-C8)cycloalkyl, -CH2-C(O)-Rc, -(CH2)-C(O)-ORc, -(CH2)-C(O)-N(Rc)2, -(CH2)2-O-Rc, -(CH2)2-S(O)2-N(Rc)2or -(CH2)2-N(Rc)S(O)2-RcRbchoose from:
(a) -H, -(C1-C6)alkyl, -(C3-C8)cycloalkyl, -(3 - to 7-membered)heterocycle, -N(Rc)2, -N(Rc)-(C3-C8)cycloalkyl or-N(Rc)-(3-to 7-membered)heterocycle; or
(b) -phenyl, -(5 - or 6-membered)heteroaryl, -N(Rc)-phenyl, or-N(Rc)-(5 - to 10-membered)heteroaryl, each of which is unsubstituted or substituted with 1, 2 or 3 independently selected R7groups;
each Rcindependently selected from-H or -(C1-C4)alkyl;
m represents an integer of 0, 1 or 2;
where Ar1is:

R1represents-Cl, -F or-CF3;
where Ar2is:
,,,,or
R14represents-H, -Cl, -F, -Br, -OCF3, -(C1-C6)alkyl, -SO2CF3, -SO2(C1-C6)alkyl, -co3, -Och3CH3or-och(CH3)2and preferably represents-CF3, -OCF3, -Cl or-F;
R14'represents-H, -Cl, -F, -Br, -CH3, -CH2CH3, -Och3, -Och(CH3)2or-och CH3;
each R8and R9independently represents-H, -Cl, -Br, -F, -CH3, -Och3, -OCH2CH3, -CF3, -OCF3, ISO-propyl or tert-butyl.

4. The compound according to any one of claims 1 to 3, where X=O.

5. The compound according to any one of claims 1 to 3, where R4represents a halogen, preferably F.

6. The compound according to any one of claims 1 to 3, where R1represents a halogen, preferably Cl or F for compounds of formula I or II, Cl, F, or CF3for compounds of formula III.

7. The compound according to any one of claims 1 to 3, where W represents s and the dotted line is absent.

8. The compound according to any one of claims 1 to 3, where W represents s and the dotted line represents a double bond.

9. The compound according to any one of claims 1 to 3, where W represents N, R4missing and the dotted line is absent.

10. The compound according to claim 1 or 2, where Ar1represents a

moreover, for compounds of formula II, n is preferably equal to 1.

11. The compound according to claim 1, where Q is a group selected from
,,,,or

12. The compound according to claim 1, where n is 1 and Q is selected from
or

13. Connect the s according to claim 1 or 2, where J is chosen from OR20or-N(R20)2and preferably represents OR20most preferably IT is.

14. The compound according to claim 1 or 2, where R20selected from H or -(C1-C6)alkyl and preferably represents N.

15. The compound according to claim 1, where Z2independently selected from H or (C1-C6)alkyl and preferably represents N.

16. The compound according to claim 1, where Z1represents H or-CH2OR7and preferably represents N.

17. The compound according to claim 1, where Z2selected from H1-(C1-C6)alkyl or-CH2OR7and preferably represents N.

18. The compound according to claim 1 or 2, where Ar2represents a
.

19. The compound according to claim 1 or 2, where Ar2represents a

and where to compounds of the formula I R14preferably independently selected from halogen, C(halogen)3, -(C1-C6)alkyl, OR7OS, (halogen)3or SO2C(halogen)3and for compounds of formula II, R14preferably independently selected from H, halogen, C(halogen)3, -(C1-C6)alkyl, OR7OS, (halogen)3or SO2C(halogen)3preferably from halogen, C(halogen)3or OS(halogen)3.

20. With the Association according to claim 1 or 2, where halogen represents F or Cl.

21. The compound according to claim 1 or 2, where s or q is 1 or 2.

22. The compound according to claim 1 or 2, where Ar2represents a

and where R8and R9independently selected from H, halogen and -(C1-C6)alkyl and preferably from H, or halogen, where halogen represents a C1or F.

23. The compound according to claim 2, where Z1represents N, OR7or CH2OR7and preferably represents OR7where R7preferably represents H or (C1-C6)alkyl.

24. The compound according to claim 2, where Z1is a HE or CH2OH.

25. The compound according to claim 1 or 2, where Ar2represents 2-pyridyl or phenyl, s or q is 1 and R14the Deputy at the 4-position Ar2the Deputy.

26. The compound according to claim 1 or 2, where Ar2represents 2-pyridyl or phenyl, s, or q is 2 and R14the substituent in the 3 - and 4-position Ar2the Deputy.

27. The compound according to claim 2, where R1represents Cl, Z2represents N and Z3represents N.

28. The compound according to claim 2, where R1represents Cl, R4represents F, Z2represents N and Z3represents N.

29. The compound according to any one of claims 1 to 3, where m is equal to 0.

30. The compound according to any one of p, where m is equal to 1, and preferably R3is a (C1-C6)alkyl, most preferably-CH3or-CH2CH3.

31. The compound according to claim 3, where Ar2choose from
,,,or.

32. The compound according to claim 3, where Ar2represents a
a)
or
b)

where R14selected from-H, -Cl, -F, -Br, -OCF3, -(C1-C6)alkyl, SO2CF3, SO2(C1-C6)alkyl, -co3, -OCH2CH3, -Och(CH3)2and preferably represents-CF3, -OCF3, -Cl or-F,
in)
,
where R14'selected from-H, -Cl, -F, -Br, -OCF3, -(C1-C6)alkyl, SO2CF3, SO2(C1-C6)alkyl, -co3, -OCH2CH3, -Och(CH3)2and preferably represents-CF3, -OCF3, -Och3, -OCH2CH3, -Cl or-F,
g)
,
where R14'selected from-H, -Cl, -F, -Br, -OCF3, -(C1-C6)alkyl, SO2CF3, SO2(C1-C6)alkyl, -co3, -OCH2CH3, -Och(CH3)2and preferably Ave is dstanley a-CF 3, -OCF3The co3, OCH2CH3, -Cl or-F,
d)

or
e)

where each R8and R9independently represents-H, -Cl, -Br, -F, -CH3, -Och3, -OCH2CH3, -CF3, -OCF3, ISO-propyl or tert-butyl.

33. The compound according to claim 3, where the chiral carbon atom of the Q-group has the (S)-configuration:
.
or (R)-configuration:
.

34. The compound according to claim 2, where
a) W represents S, X represents O, Z1is a HE and J represents-HE,
b) W represents S, X represents O, Z1represents-CH2OH and J is a HE.
c) W represents s, where the dotted line represents a double bond, X represents O, Z1is a HE, J represents-HE, R1represents a halogen and Ar1represents a

d) W represents C, the dotted line represents a double bond, X represents O, Z1represents-CH2OH, J is a-IT, R1represents a halogen and Ar1represents a

e) W represents S, X represents O, Z1pre who is HE, J represents-HE, R1is a halogen, R4represents a halogen and Ar1represents a

f) W represents S, X represents O, Z1represents-CH2OH, J is a-IT, R1is a halogen, R4represents a halogen and Ar1represents a

g) W represents s, where the dotted line represents a double bond, X represents O, Z1is a HE, J represents-HE, R1represents halogen, Ar1represents a

and Ar2represents a

h) W represents C, the dotted line represents a double bond, X represents O, Z1represents-CH2OH, J is a-IT, R1represents halogen, Ar1represents a
,
and Ar2represents a

i), W represents S, X represents O, Z1is a HE, J represents-HE, R1is a halogen, R4represents halogen, Ar1represents a
,
NCI 2represents a

j) W represents S, X represents O, Z1represents-CH2OH, J is a-IT, R1is a halogen, R4represents halogen, Ar1represents a
,
and Ar2represents a

k) W represents C, the dotted line represents a double bond, X represents O, Z1is a HE, J represents-HE, R1represents halogen, Ar1represents a
,
and Ar2represents a

l) W represents C, the dotted line represents a double bond, X represents O, Z1represents-CH2OH, J is a-IT, R1represents halogen, Ar1represents a
,
and Ar2represents a

m) W represents S, X represents O, Z1is a HE, J represents-HE, R1is a halogen, R4represents halogen, Ar1represents a

and Ar2represents a

n) W represents S, X represents O, Z1represents-CH2OH, J is a-IT, R1is a halogen, R4represents halogen, Ar1represents a

and Ar2represents a

35. The connection 34, where for options g), (h), k) or l) R1represents-Cl, Z2represents-H, and Z3is a-H.

36. The connection 34, where for options (i), j), (m) or (n) R1represents-Cl, Z2represents-H, and Z3is a-H.

37. The compound according to claim 3 having the formula

or its pharmaceutically acceptable salt, where
R1represents-Cl, -F, -CF3or-CH3;
R3represents-CH3or-CH2CH3;
R8and R9independently represents-H, -Cl, -Br, -F, -CH3, -Och3, -OCH2CH3, -CF3, -OCF3, ISO-propyl or tert-butyl.

38. The connection clause 37, where R8and R9each independently represents-H, -Cl, -Br, -F, -CH3, -Och3, -OCH2CH3, -CF3or-OCF3.

39. The connection clause 37 or 38, where R1is a-F and F3represents-CH3.

40. The compound according to claim 3, have the formula

or its pharmaceutically acceptable salt.

41. The compound according to any one of claims 1 to 3, where the pharmaceutically acceptable derivative is a pharmaceutically acceptable salt.

42. The connection at paragraph 41, where the pharmaceutically acceptable salt is a fumarate.

43. Composition for treating or preventing pain, UI, an ulcer, IBD, or IBS, containing a compound according to any one of claims 1 to 42, or its pharmaceutically acceptable derivative and a pharmaceutically acceptable carrier or excipient.

44. Method of inhibiting TRPV1 function in a cell, including the interactions of cells capable of expression of TRPV1 with an effective amount of a compound according to any one of claims 1 to 42, or its pharmaceutically acceptable derivatives.

45. A method of treating or preventing pain, UI, an ulcer, IBD, or IBS in animals, including the introduction of animals in need, an effective amount of a compound according to any one of claims 1 to 42, or its pharmaceutically acceptable derivative.

46. The compound according to any one of claims 1 to 42 for use as a medicinal product for treating or preventing pain, UI, an ulcer, IBD, or IBS.



 

Same patents:

FIELD: chemistry.

SUBSTANCE: invention relates to novel compounds of formula (I)

, where: n equals 0, 1, 2; G denotes CH2, CHR3; R1 denotes H, C1-C6-alkyl, C3-C6-alkenyl, -CH2Ph; R2, R3, R4 independently denote H, CH3, -CH2F, -CHF2, CF3; A denotes 1,4-Ph, 1,3-Ph, which can be optionally substituted with 1-4 substitutes selected from halogen, C1-C4-alkyl, C1-C4alkoxy, fluorinated C1-C4-alkyl and fluorinated C1-C4alkoxy; E denotes NR5, where R5 denotes H, C1-C3-alkyl; Ar denotes a radical of formula

and

where: Ra denotes halogen, C1-C6-alkyl, fluorinated C1-C6-alkyl, C1-C6-alkoxy, fluorinated C1-C6-alkoxy, phenyl sulphonyl, CN, -NR6R7, where R6 and R7, together with an N atom, form a 5- or 6-member saturated ring or denotes a 5-member saturated or unsaturated aromatic or non-aromatic heterocyclic ring containing, as ring members, 1, 2 or 3 heteroatoms selected from N, O and S, and where the heterocyclic ring can carry 1, 2 or 3 substitutes selected from halogen and C1-C6-alkyl, or denotes a 6-member saturated heterocyclic ring containing, as ring members, one N and one O atom; Rb and Rc independently denote H, halogen, CH3, OCH3, CH2F, OCH2F, CHF2, OCHF2, CF3, OCF3, CH2CH2F, OCH2CH2F, CH2CHF2, OCH2CHF2, CH2CF3 or OCH2CF3; Rd denotes Ra or a 5- or 6-member heteroaromatic ring containing, as ring members, 1, 2 or 3 heteroatoms selected from N, O and S, and where the heteroaromatic ring can carry 1 substitute selected from C1-C6-alkyl and C1-C6-alkylthio; Re denotes H or is defined as Ra; Rf is defined as Ra; k equals 0, 1, 2, 3; j equals 0, 1, 2, 3, 4; provided that Ra does not denote F, CH2F, CHF2, CF3, OCF3, if A denotes 1,4-Ph, Ar denotes a radical of formula (A) and Rb and Rc denote H, halogen; except compounds, where R1 denotes propyl, G denotes CH2, n equals 1, A denotes 1,4- Ph, E denotes NH, Ar denotes a radical of formula (F) and Rd denotes halogen, C1-C6-alkyl, C2-C6-alkenyl or a 5-member heteroaromatic ring; and physiologically acceptable acid addition salts thereof.

EFFECT: compounds exhibit 5HT6 receptor simulating activity, which allows for their use in a pharmaceutical composition.

25 cl, 6 tbl, 107 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to compounds of general formula (I) X represents NH, n means a number equal to 0-3, Y represents a direct bond, -(CH2)pO-, -(CH2)q- or -(CH2)qSO2-, p means a number equal to 0-2, q means a number equal to 1-3, R1 represents hydrogen, -(CR4R5)P-A-R6 or -(CR4R5)q-R6, R2 represents halogen, C1-C3-alkyl or trifluoromethyl, or represents 5~6-member heteroaryl or heterocyclyl each of which has 1 -3 heteroatoms selected from N and O, or represents optionally substituted C1-C3-alkylsulphonyl 6~12-member aryl, R3 represents R7-X-B-X'-, B represents a direct bond or represents 5~6-member heterocyclyl or heteroaryl each of which optionally contains oxo, optionally condensed and has 1-4 heteroatoms selected from N, O and S. Also the invention refers to a pharmaceutical composition for glucokinase activation and a method for preparing it.

EFFECT: use of the compounds of formula (I) as glucokinase activators.

22 cl, 11 dwg, 3 tbl, 222 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a novel heteroaryl-substituted derivative of benzothiazole - 2-[6-(methylamino)pyridin-3-yl]-1,3-benzothiazol-6-ol where one or more atoms may be a detectable isotope, in form of a free base or pharmaceutically acceptable salt thereof, capable of binding with amyloid deposits, to pharmaceutical compositions based on the radioactive-labelled disclosed compound, to use of the detectable isotope-labelled disclosed compound for determining amyloid deposits, as well as use of the disclosed compound in producing a medicinal agent for preventing and/or treating Alzheimer's disease and familial Alzheimer's disease. The present invention also relates to a novel intermediate compound for producing the disclosed heteroaryl-substituted benzothiazole derivative

EFFECT: high efficiency of using the compounds during treatment.

15 cl, 1 tbl, 15 dwg, 82 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: present invention refers to a compound of formula

wherein R1, R2 and X are those as specified in cl.1 of the patent claim, or its pharmaceutically acceptable salt, as well as using such compound or its pharmaceutically acceptable salt for preparing a drug preparation for prevention and treatment of all types of sleeping, eating or drinking disorders.

EFFECT: preparing the new azetidine compounds showing activity of orexin receptor antagonists.

12 cl, 112 ex, 1 tbl

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to 2-piperidino-5-(thienyl-2)-6H-1,3,4-thiadiazines, hydrobromides (of general formula I) and 2-piperidino-5-(thienyl-3)-6H-1,3,4-thiadiazines, hydrobromides (of general formula II) which possess antiaggregant action. wherein R=H; Cl; Br R1=H; Cl.

EFFECT: given compounds may be used for preparing cardiologic drugs and enable better treatment of various cardiovascular diseases, including myocardial infarction and thrombotic apoplexy.

1 cl, 2 tbl, 5 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a novel purified compound PM 181104 of formula I

(with molecular weight 1514 and molecular formula C69H66N18O13S5), pharmaceutically acceptable salts thereof, methods for synthesis via fermentation of a microorganism of the type Kocuria (ZMA B-1 / MTCC 5269), as well as pharmaceutical compositions.

EFFECT: high efficiency of using the composition to produce a medicinal agent for treating bacterial infections.

20 cl, 4 dwg, 4 tbl, 16 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a compound of formula

or tautomer thereof

or enantiomer or physiologically acceptable salt, where R1 is o-bromo, R2 is n-fluoro, R3 is C1-C4 alkyl, R6 is thiazolyl-2-yl, X is methylene and Z is morpholinyl. The invention also relates to methods of producing (versions) compounds of formula (I) and (Ia). The compound of formula (I) or (Ia) is used to prepare a pharmaceutical composition for treating or preventing HBV infections and HBV-induced diseases such as hepatitis B.

EFFECT: bromophenyl substituted thiazolyl dihydropyrimidines for HBV infection control.

20 cl, 7 tbl, 14 ex

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of formula I:

or pharmaceutically acceptable salts thereof, in which Q is a divalent or trivalent radical selected from C6-10aryl and heteroaryl; where said aryl or heteroaryl in Q is optionally substituted up to 3 times with radicals independently selected from halogen, C1-6 alkyl, C1-6 alkyl substituted with halogen, C1-6 alkoxy group, C1-6 alkoxy group substituted with halogen, -C(O)R20 and -C(O)OR20; where R20 is selected from hydrogen and C1-6 alkyl; and where optionally, the carbon atom neighbouring W2 can be bonded through CR31 or O with a carbon atom of Q to form a 5-member ring condensed with A and Q rings; where R31 is selected from hydrogen and C1-6 alkyl; W1 and W2 are independently selected from CR21 and N; where R21 is selected from hydrogen and -C(O)OR25; where R25 denotes hydrogen; ring A can contain up to 2 carbon ring atoms substituted with a group selected from -C(O)-, -C(S)- and -C(=NOR30)- and can be partially unsaturated and contain up to 2 double bonds; where R30 denotes hydrogen ; L is selected from C1-6alkylene, C2-6alkenylene, -OC(O)(CH2)n-, -NR26(CH2)n- and -O(CH2)n-; where R26 is selected from hydrogen and C1-6 alkyl; where n is selected from 0, 1, 2, 3 and 4; q is selected from 0 and 1; t1, t2, t3 and t4 are each independently selected from 0, 1 and 2; R1 is selected from -X1S(O)0-2X2R6a, -X1S(O)0-2X2OR6a, -X1S(O)0-2X2C(O)R6a, -X1S(O)0-2X2C(O)OR6a, -X1S(O)0-2X2OC(O)R6a and -X1S(O)0-2NR6aR6b; where X1 is selected from a bond, O, NR7a and C1-4alkylene; where R7a is selected from hydrogen and C1-6alkyl; X2 is selected from a bond and C1-6alkylene; R6a is selected from hydrogen, cyanogroup, halogen, C1-6alkyl, C2-6alkenyl, C6-10aryl, heteroaryl, heterocycloalkyl and C3-8cycloalkyl; where said aryl, heteroaryl, cycloalkyl and heterocycloalkyl in R6a is optionally substituted with 1-3 radicals independently selected from hydroxy group, halogen, C1-6alkyl, C1-6alkyl substituted with a cyano group, C1-6alkoxy group and C6-10aryl-C1-4alkoxy group; and R6b is selected from hydrogen and C1-6alkyl; R3 is selected from hydrogen, halogen, hydroxy group, C1-6alkyl, C1-6alkyl substituted with halogen, C1-6alkyl substituted with a hydroxy group, C1-6alkoxy group, C1-6alkoxy group substituted with halogen, -C(O)R23 and -C(O)OR23; where R23 is selected from hydrogen and C1-6alkyl; R4 is selected from R8 and -C(O)OR8; where R8 is selected from C1-6alkyl, heteroaryl, C3-8cycloalkyl and heterocycloalkyl; where said heteroaryl, cycloalkyl or heterocycloalkyl in R8 is optionally substituted with 1-3 radicals independently selected from halogen, C1-6alkyl, C3-8cycloalkyl and C1-6alkyl substituted with halogen; R5 is selected from hydrogen, C1-6alkyl substituted with a hydroxy group, and a C1-6alkoxy group; heteroaryl denotes a monocyclic or condensed bicyclic aromatic ring complex containing 5-9 carbon atoms in the ring, where one or more ring members are heteroatoms selected from nitrogen, oxygen and sulphur, and heterocycloalkyl denotes a saturated monocyclic 4-6-member ring in which one or more said carbon atoms in the ring are substituted with a group selected from -O-, -S- and -NR-, where R denotes a bond, hydrogen or C1-6alkyl. The invention also relates to pharmaceutical compositions containing said compounds, and methods of using said compounds to treat or prevent diseases or disorders associated with GPR119 activity, such as obesity, type 1 diabetes, type 2 sugar diabetes, hyperlipidemia, type 1 autopathic diabetes, latent autoimmune diabetes in adults, type 2 early diabetes, child atypical diabetes, adult diabetes in children, malnutrition-associated diabetes and diabetes in pregnant women.

EFFECT: improved properties of compounds.

27 cl

FIELD: chemistry.

SUBSTANCE: invention refers to the compounds of formula (I): where R denotes cycloalkyl, heterocyclil, aryl, alkyl-O-C(O)-, alkanoyl or alkyl where each cycloalkyl, heterocyclil and aryl does not necessarily contain from 1 to 3 substitutes chosen from the group including alkyl, hydroxy group, halogen, cyano group, alkoxy group, alkyl-O-C(O)-, amino group, mono- or disubstituted by alkyl amino group and heterocyclil, and where each alkyl-O-C(O)-, alkyl, alkoxy group and heterocyclil does not necessarily have additional 1 to 3 substitutes chosen from the group including a hydroxy group, alkyl, halogen, carboxy group, alkoxy group, alkyl-O-C(O)-, alkanoyl, alkyl-SO2-, amino group, mono- or disubstituted by alkyl amino group and heterocyclil; R2 denotes alkyl, cycloalkyl, cycloalkylalkyl- or alkoxy group where alkyl does not necessarily contain from 1 to 3 substitutes chosen from the alkoxy group or halogen; R3 denotes R8-O-C(O)-, (R8)(R9)N-C(O)-, R8-C(O)-, where R8 and R9 independently denote alkyl, cycloalkyl, aryl, arylalkyl-, cycloalkylalkyl- or nonaromatic heterocyclil where each alkyl, cycloalkyl, aryl, arylalkyl-, cycloalkylalkyl- and nonaromatic heterocyclil do not necessarily contain from 1 to 3 substitutes chosen from the group including a hydroxy group, carboxy group, alkyl-O-C(O)-, alkyl-C(O)-O- and alkanoyl; R4 and R5 independently denote hydrogen, alkyl, alkynyl, alkoxy group, cycloalkyl, arylalkyl-, cycloalkylalkyl-, heteroarylalkyl-, monoalkylamino-C(O)-, dialkylcmino-C(O)- or dialkylamino-C(O)-alkyl-, where both these alkyl groups do not necessarily form a ring and where each alkyl, alkynyl, cycloalkyl, arylalkyl-, cycloalkylalkyl- heteroarylalkyl-, monoalkylamino-C(O)-, dialkylamino-C(O)- or dialkylamino-C(O)-alkyl- do not necessarily contain from 1 to 3 substitutes chosen from the group including alkyl, hydroxy group, halogen, carboxy group and alkoxy group; R6 and R7 independently denote hydrogen, halogenalkyl, halogen, dialkylamino group, alkoxy group, halogenalkoxy group, heteroaryl or alkyl-S(O)2- where each heteroaryl does not necessarily contain from 1 to 3 substitutes chosen from alkyl; where "heterocyclil" denotes fully saturated or nonsaturated aromatic or nonaromatic cyclic group that is represented by 5- or 6-membered monocyclic ring system containing at least one heteroatom chosen from nitrogen, oxygen and sulphur atoms; "heteroaryl" denotes 5- or 6-membered monocyclic ring system containing from 1 to 4 heteroatoms chosen from N, O and S; or to their pharmaceutically acceptable salts and their optical isomers, or to mixtures of the optical isomers. The invention also refers to the method of inhibition of the specimen's CETP activity, to the way of treatment of the specimen's abnormality or disease mediated by CETP or responsive to CETP inhibition, to the pharmaceutical composition, and to application of the formula (I) compounds.

EFFECT: production of new bioactive compounds that inhibit the CETP.

10 cl, 71 ex

FIELD: chemistry.

SUBSTANCE: invention refers to new indazole derivants with the formula (1.0) or to their pharmaceutically acceptable salts and isomerides that act as inactivators in relation to ERK2. In formula (1.0): meanings of the chemical groups Q, R1, R2 are given in the invention formula. The invention also refers to the pharmaceutical composition containing the mentioned compounds and to application of the compounds with the formula (1.0) for production of crude drugs used in malignant growth treatment.

EFFECT: application of the compounds for production of crude drugs used in malignant growth treatment.

65 cl, 611 ex, 27 tbl

FIELD: medicine.

SUBSTANCE: invention refers to a compound which represents a biphenyl derivative of formula . What is also described is a pharmaceutical composition for treating or relieving HCV on the basis of said compound.

EFFECT: higher efficacy of the composition.

3 cl, 265 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to N-(2-thiazolyl)amide derivatives of formula wherein R1 and R2 are independently selected from H, -NO2, fluorine, chlorine and iodine, provided at least one of R1 and R2 is different from H; m is equal to 1 or 2, or to its pharmaceutically acceptable salts.

EFFECT: invention refers to a method for preparing said compounds, based pharmaceutical composition and applying them for preparing a drug for treating or preventing GSK-3 mediated diseases or conditions, especially neurodegenerative diseases, such as Alzheimer's disease or insulin-independent diabetes.

24 cl, 3 tbl, 1 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to 5-amino-3-(2-aminopropyl)-[1,2,4]thiadiazole derivatives of general formula wherein R1, R2, R3 can be identical or different independently means hydrogen, optionally substituted alkyl, optionally substituted aryl, optionally substituted aralkyl, heteroaralkyl (wherein 5- or 6-member N-, O- or S-heteroaromatic cycle), cycloalkyl, 2,2,6,6-tetramethyl-piperidin-4-yl, and also R1+R2 can mean heterocycle specified in optionally substituted pyrrolidine, piperidine, azepane, piperazine, morpholine wherein optional substitutes can be hydroxyl, cyanogroup, halogens, alkyls, lower alkoxy groups, lower alkothio groups, trihalogen methyl, sulphamide, optionally substituted amino groups (amino, dimethyl amino, diethyl amino) provided R1=H, R2 is different from hydrogen or methyl.

EFFECT: there are produced new compounds which can find application in medicine as the substances possessing neuromodulatory activity.

2 cl, 3 ex

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of general formula (I) and pharmaceutically acceptable salts thereof, where Ar denotes a phenyl group substituted with piperazine or benzo[d]thiazole, with a phenyl part bonded to B, where the piperazine or benzo[d]thiazole can be unsubstituted or substituted with substitutes selected from alkyl or acetyl; B denotes -O-; R1 denotes hydrogen; R2 denotes S(O)2R4 or C(O)(CH2)n-C(O)OR5; R3 denotes halogen; R4 denotes an aryl which can be unsubstituted or substituted with substitutes selected from a group comprising halogen, alkyl, fluoroalkyl, alkoxy and trifluoromethoxy; R5 denotes hydrogen; n is a whole number from 1 to 3. The invention also relates to a method of producing said compounds and a pharmaceutical composition for treating metabolic disorders associated with insulin resistance or hyperglycaemia, based on said compounds.

EFFECT: novel compounds are obtained, which can be used in medicine to treat type 2 diabetes, obesity, glucose intolerance, dyslipidaemia, hyperinsulinaemia, atherosclerotic disease, polycystic ovary syndrome, coronary artery disease, hypertension or non-alcoholic fatty liver disease.

28 cl, 3 dwg, 4 tbl, 22 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a method of producing amide-containing 1,3,5-dithiazinanes of general formula , where R=H (Ia), CH3 (Ib). The method is realised by reacting hydrogen sulphide-saturated aldehyde (formal or acetic) with a mixture of isonicotinic acid hydrazide - BuONa (1:3, pH>11.5). The process is carried out at ratio hydrazide: aldehyde: H2S equal to 1:3:2, at temperature 40°C while stirring constantly for 4 hours, followed by neutralisation with a calculated quantity of dilute HCl and purification via column chromatography on SiO2. The substances obtained using the disclosed method can be used as radiation protection, antitumour and diuretic agents, as well as selective sorbents and extractants of noble and precious metals.

EFFECT: obtaining amide-containing 1,3,5-dithiazinanes of general formula (I).

2 ex

FIELD: chemistry.

SUBSTANCE: invention relates to derivatives of 1,3,4-thiadiazolines (I), thiadiazinones (II) and thiadiazepines (III), obtained based on thiohydrazides of oxamic acids, which can be used to inhibit pathogenic bacteria, and can particularly affect type III secretion system in pathogens, having general formula:

, , ,

where R denotes H; R1 denotes H, pyridinyl; phenyl, substituted with alkyl C1-C5, Hal, CF3; a group , where X denotes S, substituted with alkyl C1-C5, COOR4; R2, R3 denotes alkyl C1-C5, pyridinyl, phenyl, substituted Hal, OH, OR4, a R4 denotes unsubstituted alkyl C1-C4.

EFFECT: obtaining compounds which can be used to inhibit pathogenic bacteria.

2 cl, 2 dwg, 6 tbl, 21 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to a compound of formula I wherein the substitutes A, B, B', Q and R1-R5 in formula I are specified as follows: A and B' are one of the following groups: (i) (R6)N(CH2)n, wherein n is 0 or 1; (ii) (CH2)n, wherein n is 0, 1 or 2; (iii) C(O)(CH2)n, wherein n is 0 or 1; or provided each of A and B' represents nitrogen, together they can form a bivalent radical of formula: -(CH2)s-X1-(CH2)t- (a), wherein each s and t is independently 1 or 2, and X1 represents (CH2)n, wherein n is 0 or 1; B is one of the following groups: (i) (R6)N; (ii) oxygen; (iii) C=δ, wherein δ represents oxygen or sulphur; (iv) C(R6)=C(R7); each R6 and R7 independently represent hydrogen, C1-4-alkyl; R1 is specified in the following groups: (i) phenyl group substituted by one or more substitute such as: - halogen specified in F, CI, Br or I, or alkyl1 group; aryl1 or heteroaryl group1; cyano, NH-alkyl1, N(alkyl1)(alkyl1) and amino; - NHCO-R or NHCOO-R, or COO-R, or CONH-R, wherein R represents hydrogen or alkyl group, or (ii) pyridinyl group which can be substituted by one substitute, such as halogen specified in I, F, Cl or Br; alkyl1 group; aryl1 group; cyano, NH-alkyl1, N(alkyl1)(alkyl1), and amino; -NHCO-R or NHCOO-R, or COO-R, or CONH-R, wherein R represents hydrogen or alkyl1 group; each R2, R3, R4 and R5 are independently specified in hydrogen or linear or branched alkyl group containing 1 to 10 carbon atoms; Q is specified in the following groups: (i) alkyl1; (ii) aryl1; (iii) heteroaryl1. The compounds of formula (I) are used for preparing a drug showing the c-kit inhibitor properties and aiming at treating a disease specified in neoplastic, allergic, inflammatory and autoimmune diseases.

EFFECT: use of oxazole derivatives as tyrosine kinase inhibitors.

13 cl, 1 tbl, 31 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to compounds of formula

and ,

where the ring X represents benzole or pyridine; R1 represents substituted alkyl; R2 represents optionally substituted aryl or optionally substituted 4-7-member monocyclic heterocyclic group or optionally substituted condensed group of heterocyclic group with the benzole ring where the substitutes of optionally substituted aryl, optionally substituted 4-7-member monocyclic heterocyclic group and optionally substituted condensed group of heterocyclic group with the benzole ring are selected from a group consisting of; (1) alkyl optionally substituted by a group selected from halogen and alkoxycarbonyl, (2) alkoxy optionally substituted by halogen, (3) halogen, (4) 4-7-member monocyclic heterocyclic group or (5) amino, optionally mono- or disubstituted alkyl, and (6) hydroxyl, R3 represents hydrogen or alkyl: R4 represents hydrogen, halogen or alkyl; R5 represents hydrogen or alkyl; R6 and R7 are identical or different, and each represents hydrogen or halogen; or pharmaceutically acceptable salt. Also, the invention refers to a IKur blocker containing the compounds described above as an active ingredient, and also to a preventive and therapeutic agent for cardiac arrhythmia and atrial fibrillation.

EFFECT: there are produced and described new compounds applicable as a IKur blocker effective for preventing or treating cardiac arrhythmia, such as atrial fibrillation.

12 cl, 13 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a novel compound of general formula I

,

and a pharmaceutically acceptable salt thereof, where X denotes CH2, CHF or S, Y denotes CN, R1, R2, R3 and R4 denotes hydrogen, n equals 1, m equals 0 or 1, R denotes R11, R12 or R13, where R11 includes at least one group selected from the following b) or c), where optionally substituted heterocyclic and heteroaryl groups are bonded with a noradamantyl part either directly or through a methylene adjacent group or a C-C bond or C-N bond; b) the substituted 5-member heteroaryl group, in which the heteroaryl ring is a monocyclic aromatic ring system, includes two or more heteroatoms selected from nitrogen and oxygen; c) the heterocyclic group is optionally substituted with a C1-C3 alkyl or oxo group, where the heterocyclic ring system is a 5-9-member mono- or bicyclic ring system with one or more heteroatoms selected from a group consisting of nitrogen and sulphur, where heteroatoms can also be present as functional groups, where the heterocyclic ring system can contain one or two double bonds, and where the monocyclic heterocyclic ring can be condensed with a phenyl ring, R12 is selected from hydrogen, halogen, hydroxy, amino and C1-C4 alkoxy; R13 is a substituted phenyl, where the substitutes, which can be identical or different, include at least one group selected from a) hydrogen; b) nitro, amino; c) the saturated or unsaturated monocyclic heterocyclic ring system is optionally substituted with one or more groups selected from C1-C3 alkyl and oxo, where the heterocyclic ring system is a 5-member ring with one or more heteroatoms selected from a group consisting of nitrogen and sulphur, where the heteroatoms can also be present as functional groups. The present invention also relates to a pharmaceutical composition having dipeptidyl peptidase IV inhibiting activity, methods of obtaining the novel compound of formula I and use in treating type II diabetes and diabetic complications as well as for treating dyslipidaemia, hypercholesteremia, obesity and hyperglycaemia.

EFFECT: novel dipeptidyl peptidase IV inhibitors.

10 cl, 1 tbl, 43 ex

FIELD: chemistry.

SUBSTANCE: invention refers to new indazole derivants with the formula (1.0) or to their pharmaceutically acceptable salts and isomerides that act as inactivators in relation to ERK2. In formula (1.0): meanings of the chemical groups Q, R1, R2 are given in the invention formula. The invention also refers to the pharmaceutical composition containing the mentioned compounds and to application of the compounds with the formula (1.0) for production of crude drugs used in malignant growth treatment.

EFFECT: application of the compounds for production of crude drugs used in malignant growth treatment.

65 cl, 611 ex, 27 tbl

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to a compound with formula (I): where the values of radicals Q, R1, R2, R3, R4, X and Y are as specified in Clause 1 of the patent claim or to a pharmaceutically acceptable salt of such compound or a compound ether hydrolysed in vivo provided such compound is not: {(3S)-1-[5-(adamantan-1-ylcarbamoyl)pyridine-2-yl] piperidine-3-yl} acetic acid or {(3S)-1-[5-(cyclohexylcarbamoyl)-6-(piperazine-1-yl) pyridine-2-yl] piperidine-3-yl} acetic acid or a pharmaceutically acceptable salt thereof or a compound ether hydrolysed in vivo. Additionally, the invention relates to a pharmaceutical composition containing a compound with formula I for treatment of metabolic syndrome, Type II diabetes, adiposity etc and to application of such compound with formula I for manufacture of a medication to be applied for causing an inhibition effect with regard to 11βHSD1 with a homoiothermal animal.

EFFECT: produced and described is a new compound possessing inhibition activity with regard to Type 1 human 11-β-hydroxisteroiddehydrohenase enzyme (11βHSD1).

15 cl, 187 ex

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