Glucokinase activators

FIELD: chemistry.

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

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

16 cl, 479 ex

 

The text descriptions are given in facsimile form.

1. The compound of formula (I)

and its pharmaceutically acceptable salts,
where L represents O, S, or CH2;
Y represents N or CH;
Z represents CR3;
G represents CH;
R1is a heteroaryl of calciopoli

where D1represents S, O;
D2represents N or CR12;
D3represents CR13;
R2is a (C6-C10)-aryl; 5-9-membered mono - or bicyclic heteroaryl with 1 or 2 heteroatoms independently selected from N or S; a saturated or partially unsaturated (C3-C7-cycloalkyl; or a saturated 5-6-membered heterocyclyl with 1 heteroatom selected from N, where these aryl, heteroaryl, cycloalkyl and heterocyclyl optionally substituted by one or two groups independently selected from (C1-C6)-alkyl, F, Cl, Br, CF3, CN, NO2, OR6C(=O)R6C(=O)OR6C(=O)NR6R7saturated 6-membered heterocyclyl 2 heteroatoms independently selected from N or O, and S(O)2R6and where specified alkyl optionally substituted with one group OR8;
R3represents H; (C1-C6)-alkyl, (C2-C6)-alkenyl; Cl; Br; OR6; SR6; phenyl; or 6-membered heteroaryl with 1 heteroatom selected from N, where these alkyl and alkenyl, optionally substituted by one group selected from C(=O)OR8, -OR8, -NR8R9;
or a saturated 6-membered heterocyclyl with 1 heteroatom selected from N or O;
R6and R7represent, independently, H; (C1 -C6)-alkyl; saturated (C3-C7-cycloalkyl; partially unsaturated 9-10-membered bicyclic heterocyclyl with 2-3 heteroatoms selected from N; Vnis phenyl or Vn-(5-6-membered heteroaryl with 1-4 heteroatoms independently selected from N, S or O), or Vn-(9-10-membered bicyclic heteroaryl with 2-3 heteroatoms independently selected from N, S or O), where these alkyl, heterocyclyl, phenyl and heteroaryl fragments are optionally substituted by one or two groups independently selected from (C1-C6)-alkyl, saturated (C3-C6)-cycloalkyl saturated 6-membered heterocyclyl with 1 heteroatom selected from N, NH, or S(O)2[optionally substituted C(O)O(C1-6-alkyl), C1-6-alkyl or (C1-6-alkyl)HE], Vn-phenyl, Vn-(5-6-membered heteroaryl with 1-3 heteroatoms independently selected from N and O), -F, -Cl, -Br, -I, -CF3VnCN, Vn-OR8, -C(=O)OR8, -C(=O)NR8R9Vn-NR8R9, -NR8C(O)R9;
or R6and R7together with the atoms to which they are attached, form a saturated 6-membered heterocyclic ring with 1 or 2 heteroatoms selected from N, where the aforementioned heterocyclic ring optionally substituted by one (C1-C6)-alkyl group;
R8and R9represent the th, independently H, (C1-C6)-alkyl; a saturated 5-6-membered heterocyclyl with 1-3 heteroatoms independently selected from N and O, or a saturated or partially unsaturated 7 to 9-membered bicyclic heterocyclyl with 1 heteroatom selected from N; phenyl; or 5-membered heteroaryl with 2-3 heteroatoms independently selected from N and O, where these alkyl, phenyl or heteroaryl optionally substituted by one group selected independently from (C1-C6)-alkyl, saturated 5-6-membered heterocyclyl with 1 heteroatom selected from N, -ORa, -NRaRbor-C(=O)ORa;
or R8and R9together with the atoms to which they are attached, form a saturated 5-7 membered heterocyclic ring with 1 or 2 heteroatoms selected from N, or unsaturated 9-10-membered bicyclic heterocyclic ring containing 1 heteroatom selected from N, where the aforementioned heterocyclic ring optionally substituted with one group independently selected from oxo, (C1-C6)-alkyl, or-ORa;
R12represents H or (C1-C6)-alkyl;
R13represents H; (C1-C6)-alkyl; saturated (C3-C6-cycloalkyl; saturated 5-6-membered heterocyclyl with 1 heteroatom selected from N, NH or O;
CF3; -CH2-(saturated 5-6-membered heterocyclyl with 1-2 heteroatoms, independently select the tion of N or NH); phenyl; 5-6-membered heteroaryl with 1 heteroatom independently selected from N or S; (C1-3-alkyl)(5-membered heteroaryl with 2 or 4 heteroatoms independently selected from N or O), or (CH2)n(CRxRy)C(O)NR8R9where these alkyl, heteroaryl, CH2-heterocyclyl, (C1-3-alkyl)heteroaryl and heterocyclyl, optionally substituted by one or two groups independently selected from oxo, Cl, CN, Vn-OR8C(=O)OR8C(=O)NR8R9, -NR8R9, -NR8C(=O)R9C(O)(C1-6-alkyl), C(O)-heterocyclyl where heterocyclyl represents a saturated or partially unsaturated carbocyclic radical with 3 to 12 atoms, in which at least one atom of the ring is a heteroatom selected independently from nitrogen atoms, oxygen and sulfur, SRa, SO2Rf, SO2NRcReWith(O)C1-6alkyl)NRcRdC(O)(C1-6alkyl)ORcC(=O)CH2OC(=O)(C1-6-alkyl), C(=O)CHRgNHC(=O)(C1-6-alkyl), (CH2)n(CRxRy)C(O)NH-N=CHNR8R9, (C1-C6)-alkyl or phenyl;
or R12and R13together with the atoms to which they are attached, form a 6-membered aromatic heterocyclic ring containing 1 heteroatom selected from N;
Raand Rbindependently represent H; (C1-C6)-al the sludge; phenyl; or Vn-(5-membered heteroaryl 3 heteroatoms, independently selected from N or O, where the specified Vn-heteroaryl substituted one (C1-C6)-alkyl group;
each of Rc, Reand Rgindependently represents H or (C1-C6)-alkyl;
Rdrepresents H, (C1-C6)-alkyl or C(O)O-(C1-C6)-alkyl;
Rfis a (C1-C6)-alkyl or (C1-C6-alkyl)-NH2;
Rxrepresents H or (C1-C6)-alkyl;
Ryrepresents H or-O-(C1-C6)-alkyl;
V represents alkylene with 1-6 carbon atoms, which is optionally substituted one (C1-C6)-alkyl group or a group (C1-C6-alkyl)-NRcRe;
n is 0 or 1.

2. The compound according to claim 1, where
R6and R7optionally substituted by one or two groups independently selected from (C1-C6)-alkyl; saturated (C3-C6)-cycloalkyl; saturated 6-membered-heterocyclyl with 1 heteroatom selected from N, NH or S(O)2; Vn-phenyl, Vn-(5-6-membered heteroaryl with 1-3 heteroatoms selected from N and O), -F, -Cl, -Br, -I, -CF3VnCN, Vn-OR8, -C(=O)OR8, -C(=O)NR8R9Vn-NR8R9, -NR8C(=O)R9and
R13present is employed, a H; (C1-C6)-alkyl; saturated (C3-C6-cycloalkyl; saturated 5-6-membered heterocyclyl with 1 heteroatom independently selected from N, NH or O; CF3; phenyl; 5-6-membered heteroaryl with 1 heteroatom independently selected from N or S, where these alkyl, heteroaryl and heterocyclyl optionally substituted by one or two groups independently selected from oxo, -Cl, -CN, Vn-OR8, -C(=O)OR8, -C(=O)NR8R9, -NR8R9, -NR8C(=O)R9, (C1-C6)-alkyl or phenyl;
or R12and R13together with the atoms to which they are attached, form a 6-membered aromatic heterocyclic ring containing 1 heteroatom selected from n

3. The compound according to claim 1, where R1choose from:

4. The compound according to claim 1 of formula (Ia)

where R2is a (C6-C10)-aryl, 5 to 9-membered mono - or bicyclic heteroaryl with 1 or 2 heteroatoms independently selected from N or S; a saturated or partially unsaturated (C3-C7-cycloalkyl; or a saturated 5-6-membered heterocyclyl with 1 heteroatom selected from N, where these aryl, heteroaryl and heterocyclyl optionally substituted by one or two groups independently selected from (C1-C6)-Alki is a, F, Cl, Br, CF3, CN, NO2, OR6C(=O)R6C(=O)OR6C(=O)NR6R7; saturated 6-membered heterocyclyl 2 heteroatoms independently selected from N or O, (C1-C6-alkyl)-OH, C(O)CH2NH2and C(O)CH2NR8R9and S(O)2R6;
R3represents H; (C1-C6)-alkyl; Cl; Br; OR6; SR6; phenyl; or 6-membered heteroaryl with 1 heteroatom selected from N, where the specified alkyl optionally substituted by one group selected from-C(=O)OR8, -OR8, -NR8R9or a saturated 6-membered heterocyclyl with 1 heteroatom selected from N or O;
R6and R7independently represent H; (C1-C6)-alkyl; saturated (C3-C7-cycloalkyl; partially unsaturated 9-10-membered bicyclic heterocyclyl with 2-3 heteroatoms selected from N; Vnis phenyl or Vn-(5-6-membered heteroaryl with 1-4 heteroatoms independently selected from N, S or O), or Vn-(9-10-membered bicyclic heteroaryl with 2-3 heteroatoms independently selected from N, S or O), where these alkyl, heterocyclyl, phenyl and heteroaryl fragments are optionally substituted by one or two groups independently selected from (C1-C6)-alkyl, saturated 6-membered heterocyclyl with 1 heteroatom selected from N, NH, or S(O)2[optional is entrusted substituted C(O)O(C 1-6-alkyl) or (C1-6-alkyl)-OH], phenyl, (5-6-membered heteroaryl with 1-3 heteroatoms independently selected from N or O), -F, -Cl, -Br, -I, -CF3CN, OR8C(=O)OR8C(=O)NR8R9, NR8R9, -NR8C(=O)R9or (C1-C6-alkyl)-OH;
or R6and R7together with the atoms to which they are attached, form a saturated 6-membered heterocyclic ring with 1 or 2 heteroatoms selected from N;
R8and R9independently represent H; or (C1-C6)-alkyl, where the specified alkyl optionally substituted by one group independently selected from (C1-C6)-alkyl, saturated 5-6-membered heterocyclyl with 1 heteroatom selected from N, -ORa, NRaRbor C(=O)ORa;
or R8and R9together with the atoms to which they are attached, form a saturated 5-7 membered heterocyclic ring with 1 or 2 heteroatoms selected from N, or unsaturated 9-10-membered bicyclic heterocyclic ring containing 1 heteroatom selected from N;
R12represents H or (C1-C6)-alkyl;
R13represents H; (C1-C6)-alkyl; saturated (C3-C6-cycloalkyl;
saturated 5-6-membered heterocyclyl with 1 heteroatom selected from N, NH or O;
-CH2-(saturated 5-6-membered heterocyclyl with 1-2 heteroatoms, independent is selected from N or NH); phenyl; 5-6-membered heteroaryl with 1 heteroatom independently selected from N or S; (C1-3-alkyl)(5-membered heteroaryl with 2 or 4 heteroatoms independently selected from N or O), or (CH2)n(CRxRy)C(O)NR8R9where these alkyl, heteroaryl, CH2-heterocyclyl, (C1-3-alkyl)heteroaryl and heterocyclyl, optionally substituted by one or two groups independently selected from oxo, -Cl, -CN, OR8C(=O)OR8, -C(=O)NR8R9, -NR8R9C(O)-(C1-C6)-alkyl, SRa, SO2Rf, SO2NRcReC(O)(C1-6-alkyl)NRcRdC(O)(C1-6-alkyl)ORcC(=O)CH2OC(=O)(C1-6-alkyl), (C1-C6)-alkyl, and phenyl;
or R12and R13together with the atoms to which they are attached, form a 6-membered aromatic heterocyclic ring with 1 additional heteroatom selected N;
Raand Rbindependently represent H, or (C1-C6)-alkyl;
each of Rc, Reand Rgindependently represents H or (C1-C6)-alkyl;
Rdrepresents H, (C1-C6)-alkyl or C(O)O-(C1-C6)-alkyl;
Rfis a (C1-C6)-alkyl or (C1-C6-alkyl)-NH2;
V represents alkylene with 1-4 carbon atoms, which is NeoMaster is but substituted one (C 1-C6)-alkyl group or a group (C1-C6-alkyl)-NRcRe;
n is 0 or 1.

5. The compound according to claim 1 or 3, where R12represents H.

6. The compound according to any one of claims 1, 3 or 5, where R13represents H, (C1-C6)-alkyl, saturated C3-6-cycloalkyl, hetCyc1, -CH2hetCyc2, (C1-C3)-alkyl-hetAr1, phenyl, 5-6-membered heteroaryl with 1 heteroatom independently selected from N or S, chloro-(C1-C6-alkyl), (C1-C6-alkyl)-CN, (C1-C6-alkyl)-CO2R8, (C1-C6-alkyl)-SRa, (C1-C6-alkyl)-SO2Rf, (C1-C6-alkyl)-phenyl, (C1-C6-alkyl)-OR8, (C1-C6-alkyl)-NR8R9, (CH2)n(CRxRy)C(=O)NR8R9CH2(CRxRy)C(O)OR8CH2CH(CO2H)-CH2CH2Other8, (C1-C6-alkyl)C(O)-heterocyclyl where heterocyclyl represents a saturated 5-7 membered heterocyclic ring with 1 or 2 heteroatoms independently selected from N or unsaturated 9-10-membered bicyclic heterocyclic ring containing 1 heteroatom selected from N;
where Rxand Ryrepresent, independently, H, methyl or OMe;
n is 0 or 1,
hetCyc1represents a saturated 5-6-membered heterocyclyl with a heteroatom, selected from N, NH or O, optionally substituted with one or two groups independently selected from (C1-C6)-alkyl, C(O)(C1-C6-alkyl), (C1-C6-alkyl)HE, C(O)O(C1-C6-alkyl), C(O)(C1-6-alkyl)NRcRdC(O)(C1-6alkyl)ORcC(O)NR8R9, SO2NRcRe, SO2RfC(=O)CHRgNHC(=O)(C1-6-alkyl) and C(=O)CH2OC(=O)(C1-6-alkyl);
hetCyc2represents a saturated 5-6-membered heterocyclyl with 1-2 heteroatoms, independently selected from N or NH, and optionally substituted by one or two groups independently selected from (C1-C6)-alkyl, C(O)-(C1-C6-alkyl), C(O)O(C1-C6-alkyl) carbonyl group, and
hetAr1represents a 5-membered heteroaryl with 2 or 4 heteroatoms independently selected from N or O, optionally substituted (C1-C6)-alkyl or OH.

7. The compound according to any one of claims 1, 3, 5, or 6, where R2represents a
(i) phenyl, optionally substituted by one or two groups independently selected from F, Cl, Br, CN, CF3, (C1-C6)-alkyl, NO2, SO2-(C1-C6-alkyl), OH, O-(C1-C6-alkyl), CO2H, CO2-(C1-C6-alkyl), -C(O)-partially unsaturated 9-10-membered heterocyclyl with 2-3 heteroatoms selected from N [optional samisen the th (C 1-C6)-alkyl], saturated 6-membered heterocyclyl 2 heteroatoms independently selected from N or O, and-C(O)NR6NR7;
(ii) a 5-6 membered monocyclic heteroaryl ring with 1 or 2 nitrogen atoms;
(iii) a 9-membered bicyclic heteroaryl ring with 2 heteroatoms independently selected from N or S;
(iv) a 5-membered saturated heterocyclic ring with one nitrogen atom, where the heterocyclic ring optionally is substituted by CO2-(C1-C6-alkyl), C(O)NH-(C1-C6-alkyl), C(O)CH2N(C1-C6-alkyl)2C(O)-(C1-C6-alkyl)-CO2H or SO2-(5-6-membered heteroaryl with 1-4 heteroatoms independently selected from N, S or O), or SO2-(9-10-membered bicyclic-heteroaryl with 2-3 heteroatoms independently selected from N, S or O); or
(v) a 5-6-membered saturated or partially unsaturated cycloalkyl ring.

8. The compound according to any one of claims 1, 3, 5, 6 or 7, where R3represents H, Br, Cl, SR6, OR6, phenyl or 6-membered heteroaryl with 1 heteroatom selected from N, or (C1-C6)-alkyl, where the specified alkyl optionally substituted C(O)OR, NR8R9or or8.

9. The compound according to any one of claims 1, 3, 5, 6 or 7, where R3represents a
(i) S-Vn-phenyl, where n is equal to 0, and phenyl optionally substituted with one or two groups independently selected from Cl, OH, CN, CF3, CO2H, O-(C1-C6-alkyl), O(C1-C6-alkyl)CO2H, O(C1-C6-alkyl)NR8R9or groups(saturated 6-membered heterocyclyl with 1 heteroatom selected from N, NH or S(O)2)-C(O)O(C1-C6-alkyl);
(ii) S-Vn-phenyl, where n is equal to 1, V is a (C1-C6-alkylene, optionally substituted CH2CH2NRcReand phenyl optionally substituted by F, Cl, or O-(C1-C6-alkyl);
(iii) S-Vn-(5-6-membered heteroaryl with 1-4 heteroatoms independently selected from N, S or O), where n is equal to 1, V is a (C1-C6-alkylene, optionally substituted (C1-C6)-alkyl;
(iv) S-Vn-(10-membered bicyclic heteroaryl with 2-3 heteroatoms selected from N), where n is equal to 1, V is a (C1-C6-alkylen;
(v) SR6where R6is a Vn-(9-10-membered bicyclic heteroaryl with 2-3 heteroatoms independently selected from N, S or O), n is 0, and heteroaryl group is optionally substituted by one or two groups independently selected from I, Br, (C1-C6)-alkyl and CO2H;
(vi) S-Vn-(5-6-membered heteroaryl with 1-4 heteroatoms independently selected from N and S), where n is equal to 0, and heteroaryl optionally substituted by one or two groups independently selected from Cl, CN, (C1 -C6)-alkyl, O-(C1-C6-alkyl), (C1-C6)-alkyl-NR8R9, (C1-C6-alkyl)-CN, C(=O)O(C1-C6-alkyl) and CF3;
(vii) S-CHR6aR6bwhere R6ais piperidinyl (optionally substituted C1-C6)-alkyl, CO2-(C1-C6-alkyl) or (C1-C6-alkyl) -, or structure formula

R6Arepresents pyridyl, pyrimidyl, C(O)O(C1-C6-alkyl), (C1-C6-alkyl)-OH, C(O)NH(C1-C6-alkyl), C(O)NH-heterocyclyl where heterocyclyl represents a saturated 5-6-membered heterocyclyl with 1-3 heteroatoms independently selected from N and O, or a saturated or partially unsaturated 7 to 9-membered bicyclic heterocyclyl with 1 heteroatom selected from N; or (C1-C6)-alkyl;
(viii) S - rich (C3-C7-cycloalkyl;
(ix) S - partially unsaturated 9-10-membered heterocyclyl with 2-3 heteroatoms selected from N;
(x) S-(C1-C6-alkyl)-C(O)OR8;
(xi) S-CH2C(O)-NR8-(C1-C6-alkyl)-NRaRbS-CH2C(O)-NR8-(C1-C6-alkyl)-saturated 5-6-membered heterocyclyl with 1 heteroatom selected from N, or S-(C1-C6-alkyl)-NR8R9;
(xii) OH, O-(C1-C6-alkyl), O-(C1-C6-alkyl)-phenyl, O-(C1C 6-alkyl)- saturated 6-membered heterocyclyl with 1 heteroatom selected from N, NH, or S(O)2, O-(C1-C6-alkyl)-NR8R9or O-phenyl, which is optionally substituted with Br;
(xiii) phenyl;
(xiv) a 6-membered heteroaryl with one nitrogen atom;
(xv) (C1-C6)-alkyl, (C1-C6-alkyl) - saturated 6-membered heterocyclyl with 1 heteroatom selected from N or O (C1-C6-alkyl)-OH, (C1-C6-alkyl)-CO2R8, (C1-C6-alkyl)-CO2-(C1-C6-alkyl), (C1-C6-alkyl)-NR8R9or (C2-C6alkenyl)-CO2R8; or
(xvi) Br, Cl or H.

10. The compound according to claim 2, where R1choose from:
.

11. The compound according to claim 2 or claim 10,
where G represents CH;
Y represents CH or N;
Z represents CR3;
R12represents H.

12. The compound according to any one of claim 2, 10 or 11, where R2represents a
(i) phenyl, optionally substituted by one or two groups independently selected from F, Cl, Br, CN, CF3, (C1-C6)-alkyl, NO2, SO2-(C1-C6-alkyl), OH, O-(C1-C6-alkyl), CO2H, CO2-(C1-C6-alkyl), -C(O)-partially unsaturated 9-10-membered bicyclic heterocyclyl with 2-3 gets what routename, selected from N [optionally substituted C1-C6)-alkyl], saturated 6-membered heterocyclyl 2 heteroatoms selected from N or O, and-C(O)NR6R7;
(ii) a 5-6-membered monocyclic heteroaryl with 1 or 2 nitrogen atoms;
(iii) a 9-membered bicyclic heteroaryl ring with 2 heteroatoms independently selected from N or S;
(iv) a 5-membered saturated heterocyclic ring with one nitrogen atom, where the heterocyclic ring optionally is substituted by CO2-(C1-C6-alkyl), C(O)NH-(C1-C6-alkyl), C(O)CH2N(C1-C6-alkyl)2C(O)-(C1-C6-alkyl)-CO2H or SO2-(5-6-membered heteroaryl with 1-4 heteroatoms independently selected from N, S or O), or
(v) a 5-6-membered saturated or partially unsaturated cycloalkyl ring;
R3represents H, Br, Cl, SR6, OR6, phenyl or 6-membered heteroaryl with 1 heteroatom selected from N, or (C1-C6)-alkyl, where the specified alkyl optionally substituted C(O)OR8, NR8R9or or8;
R12represents H.

13. A compound selected from the group consisting of:
2-(2-(4-methylthiazole-2-ylamino)pyridine-3-yloxy)benzonitrile;
4-(2-(4-methylthiazole-2-ylamino)pyridine-3-yloxy)benzonitrile;
2-(2-(3-methyl-1,2,4-thiadiazole-5-ylamino)pyridine-3-yloxy)benzonitrile;
N-(4-methylthiazole-yl)-3-(4-nitrophenoxy)pyridine-2-amine;
3-(4-(methylsulphonyl)phenoxy)-N-(4-methylthiazole-2-yl)pyridine-2-amine;
5-chloro-N-(4-methylthiazole-2-yl)-3-phenoxypyridine-2-amine;
N-(4-methylthiazole-2-yl)-3-phenoxy-5-(phenylthio)pyridine-2-amine;
N-(4-methylthiazole-2-yl)-3-phenoxy-5-vinylpyridin-2-amine;
5-bromo-N-(4-methylthiazole-2-yl)-3-phenoxypyridine-2-amine;
N-(4-methylthiazole-2-yl)-3-phenoxy-5-(pyridin-3-yl)pyridine-2-amine;
N-(4-methylthiazole-2-yl)-3-phenoxy-5-(pyridin-4-yl)pyridine-2-amine;
methyl 3-(6-(4-methylthiazole-2-ylamino)-5-phenoxypyridine-3-ylthio)propanoate;
N-(5-(cyclohexylthio)-3-phenoxypyridine-2-yl)-4-methylthiazole-2-amine;
N-(5-(benzylthio)-3-phenoxypyridine-2-yl)-4-methylthiazole-2-amine;
4-methyl-N-(3-phenoxy-5-(pyridine-2-immedilty)pyridine-2-yl)thiazol-2-amine;
4-methyl-N-(3-phenoxy-5-(piperidine-4-immedilty)pyridine-2-yl)thiazol-2-amine;
N-(5-chloro-3-phenoxypyridine-2-yl)-4-utiltity-2-amine;
N-(5-chloro-3-phenoxypyridine-2-yl)-4,5-dimethylthiazol-2-amine;
N-(5-chloro-3-phenoxypyridine-2-yl)-4-isobutylthiazole-2-amine;
4-butyl-N-(5-chloro-3-phenoxypyridine-2-yl)thiazol-2-amine;
N-(5-chloro-3-phenoxypyridine-2-yl)-4-cyclopropylmethyl-2-amine;
5-(2-methoxybenzylthio)-N-(4-methylthiazole-2-yl)-3-phenoxypyridine-2-amine;
5-(4-methoxybenzylthio)-N-(4-methylthiazole-2-yl)-3-phenoxypyridine-2-amine;
5-(2-chlorobenzylthio)-N-(4-methylthiazole-2-yl)-3-phenoxypyridine-2-amine;
N-(4-methylthiazole-2-yl)-3-(phenylthio)pyridine-2-amine;
3-(2-chlorophenylthio)-N-(4-methylthiazole-2-yl)pyridine-2-amine;
3-(3-IU is oxigenation)-N-(4-methylthiazole-2-yl)pyridine-2-amine;
methyl 2-(2-(4-methylthiazole-2-ylamino)pyridine-3-ylthio)benzoate;
3-(cyclopentyl)-N-(4-methylthiazole-2-yl)pyridine-2-amine;
N-(4-methylthiazole-2-yl)-3-phenoxypyridine-2-amine;
N-(4-methylthiazole-2-yl)-3-phenoxy-5-(1-(pyridin-2-yl)ethylthio)pyridine-2-amine;
5-(3-methoxybenzylthio)-N-(4-methylthiazole-2-yl)-3-phenoxypyridine-2-amine;
3-(cyclohex-2-enyloxy)-N-(4-methylthiazole-2-yl)pyridine-2-amine;
3-(cyclopentyloxy)-N-(4-methylthiazole-2-yl)pyridine-2-amine;
5-(3-(dimethylamino)propylthio)-N-(4-methylthiazole-2-yl)-3-phenoxypyridine-2-amine;
N-(5-bromo-3-(phenylthio)pyridine-2-yl)-4-methylthiazole-2-amine;
5-(2-chlorophenylthio)-6-(4-methylthiazole-2-ylamino)pyridine-3-ol;
N-(5-methoxy-3-phenoxypyridine-2-yl)-4-methylthiazole-2-amine;
methyl 3-(6-(4-methylthiazole-2-ylamino)-5-phenoxypyridine-3-yl)propanoate;
3-(6-(4-methylthiazole-2-ylamino)-5-phenoxypyridine-3-yl)propanoic acid;
3-benzyl-N-(4-methylthiazole-2-yl)pyridine-2-amine;
N-(5-bromo-3-(2-chlorophenylthio)pyridine-2-yl)-4-methylthiazole-2-amine;
N-(3-(2-chlorophenylthio)-5-(phenylthio)pyridine-2-yl)-4-methylthiazole-2-amine;
methyl 3-(5-(2-chlorophenylthio)-6-(4-methylthiazole-2-ylamino)pyridine-3-ylthio)propanoate;
N-(3-(2-chlorophenylthio)-5-(1-(pyridin-2-yl)ethylthio)pyridine-2-yl)-4-methylthiazole-2-amine;
N-(3-(2-chlorophenylthio)-5-(piperidine-4-immedilty)pyridine-2-yl)-4-methylthiazole-2-amine;
N-(3-(2-chlorophenylthio)-5-(3-(dimethylamino)propylthio)pyridine-2-yl)-4-methylthiazole-2-amine;
N-(5-(2-chlorophenylthio)-3-phenoxyphenyl the h-2-yl)-4-methylthiazole-2-amine;
N-(5-(3-chlorophenylthio)-3-phenoxypyridine-2-yl)-4-methylthiazole-2-amine;
N-(5-(2-methoxybenzylthio)-3-phenoxypyridine-2-yl)-4-methylthiazole-2-amine;
N-(5-(3-methoxyphenyl)-3-phenoxypyridine-2-yl)-4-methylthiazole-2-amine;
3-(6-(4-methylthiazole-2-ylamino)-5-phenoxypyridine-3-ylthio)phenol;
2-(3-(6-(4-methylthiazole-2-ylamino)-5-phenoxypyridine-3-ylthio)phenoxy)acetic acid;
4-methyl-N-(3-phenoxy-5-(3-(2-(piperidine-1-yl)ethoxy)phenylthio)pyridine-2-yl)thiazol-2-amine;
N-(5-(3-(3-(dimethylamino)propoxy)phenylthio)-3-phenoxypyridine-2-yl)-4-methylthiazole-2-amine;
1-(3-(5-bromo-2-(4-methylthiazole-2-ylamino)pyridine-3-yloxy)pyrrolidin-1-yl)Etalon;
1-(3-(5-bromo-2-(4-methylthiazole-2-ylamino)pyridine-3-yloxy)pyrrolidin-1-yl)-2-(dimethylamino)Etalon;
3-(5-bromo-2-(4-methylthiazole-2-ylamino)pyridine-3-yloxy)-N-isopropylpyrimidine-1-carboxamide;
N-(5-bromo-3-(1-(1-methyl-1H-imidazol-4-ylsulphonyl)pyrrolidin-3-yloxy)pyridine-2-yl)-4-methylthiazole-2-amine;
5-(2-forbesii)-N-(4-methylthiazole-2-yl)-3-phenoxypyridine-2-amine;
N-(4-methylthiazole-2-yl)-3-phenoxy-5-(1-(pyridin-2-yl)propylthio)pyridine-2-amine;
2-((6-(4-methylthiazole-2-ylamino)-5-phenoxypyridine-3-ylthio)methyl)pyridine-3-ol;
3-(2-(3-phenoxy-5-(1-(pyridin-2-yl)ethylthio)pyridine-2-ylamino)thiazol-4-yl)propanoic acid;
4-chloro-3-(2-(4-methylthiazole-2-ylamino)-5-(phenylthio)pyridine-3-yloxy)benzoic acid;
4-chloro-N-(2-(dimethylamino)ethyl)-3-(2-(4-methylthiazole-2-ylamino)-5-(phenylthio)pyridin-yloxy)benzamide;
4-chloro-3-(2-(4-methylthiazole-2-ylamino)-5-(1-(pyridin-2-yl)ethylthio)pyridine-3-yloxy)benzoic acid;
4-chloro-N-(2-(dimethylamino)ethyl)-3-(2-(4-methylthiazole-2-ylamino)-5-(1-(pyridin-2-yl)ethylthio)pyridine-3-yloxy)benzamide;
N-(3-(2,6-dichlorophenylthio)pyridine-2-yl)-4-methylthiazole-2-amine;
4-methyl-N-(3-(naphthalene-2-ylthio)pyridine-2-yl)thiazol-2-amine;
N-(5-(2-chlorophenylthio)-3-phenoxypyridine-2-yl)-4-methylthiazole-2-amine;
N-(5-(3-chlorophenylthio)-3-phenoxypyridine-2-yl)-4-methylthiazole-2-amine;
N-(5-(2-methoxybenzylthio)-3-phenoxypyridine-2-yl)-4-methylthiazole-2-amine;
N-(5-(3-methoxyphenyl)-3-phenoxypyridine-2-yl)-4-methylthiazole-2-amine;
methyl 3-(5-(2-chlorophenylthio)-6-(4-methylthiazole-2-ylamino)pyridine-3-ylthio)propanoate;
N-(5-(2,5-dimethoxyphenylthio)-3-phenoxypyridine-2-yl)-4-methylthiazole-2-amine;
N-(5-(2,5-dichlorophenylthio)-3-phenoxypyridine-2-yl)-4-methylthiazole-2-amine;
N-(5-(2,5-dimethylphenyl)-3-phenoxypyridine-2-yl)-4-methylthiazole-2-amine;
N-(5-(1-(2-(dimethylamino)ethyl)-1H-tetrazol-5-ylthio)-3-phenoxypyridine-2-yl)-4-methylthiazole-2-amine;
4-methyl-N-(5-(4-methyl-4H-1,2,4-triazole-3-ylthio)-3-phenoxypyridine-2-yl)thiazol-2-amine;
3-(2-chlorophenylthio)-N-(4-methylthiazole-2-yl)-5-(phenylthio)pyridine-2-amine;
N-(5-([1,2,4]triazolo[4,3-a]pyridine-3-ylthio)-3-phenoxypyridine-2-yl)-4-methylthiazole-2-amine;
2-(4-methyl-5-(6-(4-methylthiazole-2-ylamino)-5-phenoxypyridine-3-ylthio)-4H-1,2,4-triazole-3-yl)acetonitrile;
methyl 3-(6-(4-penetrtion-2-ylamino)-5-phenoxypyridine--ylthio)propanoate;
methyl 3-(6-(4-(1-methylpiperidin-4-yl)thiazol-2-ylamino)-5-phenoxypyridine-3-ylthio)propanoate;
methyl 3-(5-(4-pertenece)-6-(4-penetrtion-2-ylamino)pyridine-3-ylthio)propanoate;
methyl 3-(5-(2-chlorophenylthio)-6-(4-methylthiazole-2-ylamino)pyridine-3-ylthio)propanoate;
methyl 3-(6-(4-methylthiazole-2-ylamino)-5-(phenylthio)pyridine-3-ylthio)propanoate;
tert-butyl 4-(5-(3-(4-pertenece)-5-(3-methoxy-3-oxopropyl)pyridine-2-ylamino)-1,2,4-thiadiazole-3-yl)piperidine-1-carboxylate;
tert-butyl 4-((5-(3-(4-pertenece)-5-(3-methoxy-3-oxopropyl)pyridine-2-ylamino)-1,2,4-thiadiazole-3-yl)methyl)piperidine-1-carboxylate;
N-(3-(2-chlorophenylthio)-5-(1-(pyridin-2-yl)ethylthio)pyridine-2-yl)-4-methylthiazole-2-amine;
N-(3-(2-chlorophenylthio)-5-(piperidine-4-immedilty)pyridine-2-yl)-4-methylthiazole-2-amine;
N-(3-(2-chlorophenylthio)-5-(3-(dimethylamino)propylthio)pyridine-2-yl)-4-methylthiazole-2-amine;
4-phenethyl-N-(3-phenoxy-5-(piperidine-4-immedilty)pyridine-2-yl)thiazol-2-amine;
3-(6-(4-methylthiazole-2-ylamino)-5-phenoxypyridine-3-ylthio)phenol;
4-methyl-N-(3-phenoxy-5-(3-(2-(piperidine-1-yl)ethoxy)phenylthio)pyridine-2-yl)thiazol-2-amine;
2-(3-(6-(4-methylthiazole-2-ylamino)-5-phenoxypyridine-3-ylthio)phenoxy)acetic acid;
N-(5-(3-(3-(dimethylamino)propoxy)phenylthio)-3-phenoxypyridine-2-yl)-4-methylthiazole-2-amine;
1-(3-(5-bromo-2-(4-methylthiazole-2-ylamino)pyridine-3-yloxy)pyrrolidin-1-yl)Etalon;
1-(3-(5-bromo-2-(4-methylthiazole-2-ylamino)pyridine-3-yloxy)p is Raiden-1-yl)-2-(dimethylamino)Etalon;
4-(3-(5-bromo-2-(4-methylthiazole-2-ylamino)pyridine-3-yloxy)pyrrolidin-1-yl)-4-oxobutanoic acid;
3-(5-bromo-2-(4-methylthiazole-2-ylamino)pyridine-3-yloxy)-N-isopropylpyrimidine-1-carboxamide;
N-(5-bromo-3-(1-(1-methyl-1H-imidazol-4-ylsulphonyl)pyrrolidin-3-yloxy)pyridine-2-yl)-4-methylthiazole-2-amine;
N-(5-bromo-3-(2-chlorophenylthio)pyridine-2-yl)-4-methylthiazole-2-amine;
4-methyl-N-(3-phenoxy-5-(pyridine-2-ylthio)pyridine-2-yl)thiazol-2-amine;
4-methyl-N-(3-phenoxy-5-(pyridine-4-ylthio)pyridine-2-yl)thiazol-2-amine;
4-methyl-N-(3-phenoxy-5-(pyrimidine-2-ylthio)pyridine-2-yl)thiazol-2-amine;
4-methyl-N-(5-(6-methylpyridin-2-ylthio)-3-phenoxypyridine-2-yl)thiazol-2-amine;
4-methyl-N-(5-(4-methylthiazole-2-ylthio)-3-phenoxypyridine-2-yl)thiazol-2-amine;
N-(3-(2-chlorophenylthio)-5-(pyridine-4-ylthio)pyridine-2-yl)-4-methylthiazole-2-amine;
4-(1-methylpiperidin-4-yl)-N-(3-phenoxy-5-(phenylthio)pyridine-2-yl)thiazol-2-amine;
N-(3,5-bis(phenylthio)pyridine-2-yl)-4-methylthiazole-2-amine;
4-methyl-N-(3-(phenylthio)-5-(pyridine-2-ylthio)pyridine-2-yl)thiazol-2-amine;
3-methyl-N-(3-(phenylthio)-5-(pyridine-2-ylthio)pyridine-2-yl)-1,2,4-oxadiazol-5-amine;
3-methyl-N-(3-phenoxy-5-(pyridine-2-ylthio)pyridine-2-yl)-1,2,4-thiadiazole-5-amine;
N-(5-(4-methoxybenzylthio)-3-phenoxypyridine-2-yl)-3-methyl-1,2,4-thiadiazole-5-amine;
N-(3-(4-pertenece)-5-(pyridine-2-ylthio)pyridine-2-yl)-3-isobutyl-1,2,4-thiadiazole-5-amine;
(6-(4-methylthiazole-2-ylamino)-5-phenoxypyridine-3-yl)methanol;
N-(5-(4-(dimethylamino)b is t-1-enyl)-3-phenoxypyridine-2-yl)-4-methylthiazole-2-amine;
5-(4-(dimethylamino)butyl)-N-(4-methylthiazole-2-yl)-3-phenoxypyridine-2-amine;
5-(2-chloropyridin-4-ylthio)-N-(4-methylthiazole-2-yl)-3-phenoxypyridine-2-amine;
N-(5-(2-chloropyrimidine-4-ylthio)-3-phenoxypyridine-2-yl)-4-methylthiazole-2-amine;
5-(4,6-dimethylpyrimidin-2-ylthio)-N-(4-methylthiazole-2-yl)-3-phenoxypyridine-2-amine;
N-(5-(4,6-dimethoxypyrimidine-2-ylthio)-3-phenoxypyridine-2-yl)-4-methylthiazole-2-amine;
5-(4-methoxypyridine-2-ylthio)-N-(4-methylthiazole-2-yl)-3-phenoxypyridine-2-amine;
N-(4-methylthiazole-2-yl)-3-phenoxy-5-(thieno[3,2-b]pyridine-7-ylthio)pyridine-2-amine;
4-methyl-N-(5-(3-methylisoxazole[5,4-b]pyridine-4-ylthio)-3-phenoxypyridine-2-yl)thiazol-2-amine;
N-(5-(2-(methoxymethyl)pyrimidine-4-ylthio)-3-phenoxypyridine-2-yl)-4-methylthiazole-2-amine;
4-phenethyl-N-(3-phenoxy-5-(thieno[3,2-b]pyridine-7-ylthio)pyridine-2-yl)thiazol-2-amine;
N-(5-(3-methylisoxazole[5,4-b]pyridine-4-ELTA)-3-phenoxypyridine-2-yl)-4-penetrtion-2-amine;
N-(5-(5-methylpyrazolo[1,5-a]pyrimidine-7-ylthio)-3-phenoxypyridine-2-yl)-4-penetrtion-2-amine;
4-phenethyl-N-(3-phenoxy-5-(thieno[3,2-d]pyrimidine-4-ylthio)pyridine-2-yl)thiazol-2-amine;
4-methyl-N-(5-(5-methylpyrazolo[1,5-a]pyrimidine-7-ylthio)-3-phenoxypyridine-2-yl)thiazol-2-amine;
4-methyl-N-(3-phenoxy-5-(thieno[3,2-d]pyrimidine-4-ylthio)pyridine-2-yl)thiazol-2-amine;
4-(1-methylpiperidin-4-yl)-N-(3-phenoxy-5-(thieno[3,2-b]pyridine-7-ylthio)pyridine-2-yl)thiazol-2-amine;
N-(5-(3-methylisoxazole[5,4-b]pyridine-4-ylthio)-3-phenoxypyridine-2-is)-4-(1-methylpiperidin-4-yl)thiazol-2-amine;
N-(5-(2-Jomtien[3,2-b]pyridine-7-ylthio)-3-phenoxypyridine-2-yl)-4-methylthiazole-2-amine;
4-methyl-N-(5-(2-methylthieno[3,2-b]pyridine-7-ylthio)-3-phenoxypyridine-2-yl)thiazol-2-amine;
N-(5-(2-methylthieno[3,2-b]pyridine-7-ylthio)-3-phenoxypyridine-2-yl)-4-penetrtion-2-amine;
N-(5-(2,5-dimethylpyrazolo[1,5-a]pyrimidine-7-ylthio)-3-phenoxypyridine-2-yl)-4-penetrtion-2-amine;
N-(3-(4-pertenece)-5-(thieno[3,2-b]pyridine-7-ylthio)pyridine-2-yl)-4-penetrtion-2-amine;
N-(3-(4-pertenece)-5-(3-methylisoxazole[5,4-b]pyridine-4-ylthio)pyridine-2-yl)-4-penetrtion-2-amine;
N-(3-(4-pertenece)-5-(5-methylpyrazolo[1,5-a]pyrimidine-7-ylthio)pyridine-2-yl)-4-penetrtion-2-amine;
N-(5-(2,5-dimethylpyrazolo[1,5-a]pyrimidine-7-ylthio)-3-(4-pertenece)pyridine-2-yl)-4-penetrtion-2-amine;
N-(3-(4-pertenece)-5-(2-methylthieno[3,2-b]pyridine-7-ylthio)pyridine-2-yl)-4-penetrtion-2-amine;
4-(6-(4-methylthiazole-2-ylamino)-5-phenoxypyridine-3-ylthio)benzonitrile;
N-(3-(2-chlorophenylthio)-5-(thieno[3,2-b]pyridine-7-ylthio)pyridine-2-yl)-4-methylthiazole-2-amine;
4-(5-phenoxy-6-(4-(piperidine-4-yl)thiazol-2-ylamino)pyridine-3-ylthio)benzonitrile;
N-(5-(furo[3,2-C]pyridine-4-ylthio)-3-phenoxypyridine-2-yl)-4-methylthiazole-2-amine;
N-(5-(2-Jomtien[3,2-b]pyridine-7-ylthio)-3-phenoxypyridine-2-yl)-4-(piperidine-4-yl)thiazol-2-amine;
4-methyl-N-(3-(phenylthio)-5-(thieno[3,2-b]pyridine-7-ylthio)pyridine-2-yl)thiazol-2-amine;
4-methyl-N-(5-(3-methylisoxazole[5,4-b]pyridine-4-ylthio)-3-(phenylthio)pyridine-2-is)thiazol-2-amine;
4-(6-(4-methylthiazole-2-ylamino)-5-(phenylthio)pyridine-3-ylthio)benzonitrile;
4-methyl-N-(3-(phenylthio)-5-(5,6,7,8-tetrahydropyrido[4,3-d]pyrimidine-4-ylthio)pyridine-2-yl)thiazol-2-amine;
tert-butyl 4-(5-(3-(4-pertenece)-5-(thieno[3,2-b]pyridine-7-ylthio)pyridine-2-ylamino)-1,2,4-thiadiazole-3-yl)piperidine-1-carboxylate;
N-(4-cyclopropylmethyl-2-yl)-3-phenoxy-5-(pyridine-4-ylthio)pyridine-2-amine;
4-isobutyl-N-(3-phenoxy-5-(pyridine-4-ylthio)pyridine-2-yl)thiazol-2-amine;
4-cyclohexyl-N-(3-phenoxy-5-(pyridine-4-ylthio)pyridine-2-yl)thiazol-2-amine;
N-(3-phenoxy-5-(pyridine-4-ylthio)pyridine-2-yl)-4-(trifluoromethyl)thiazol-2-amine;
methyl 3-(2-(3-phenoxy-5-(pyridine-4-ylthio)pyridine-2-ylamino)thiazol-4-yl)propanoate;
N-(3-phenoxy-5-(pyridine-4-ylthio)pyridine-2-yl)-4-(pyridin-2-yl)thiazol-2-amine;
N-(3-phenoxy-5-(pyridine-4-ylthio)pyridine-2-yl)-4-phenylthiazol-2-amine;
N-(3-phenoxy-5-(pyridine-4-ylthio)pyridine-2-yl)-4-(thiophene-3-yl)thiazol-2-amine;
4-phenethyl-N-(3-phenoxy-5-(pyridine-4-ylthio)pyridine-2-yl)thiazol-2-amine;
4-ethyl-N-(3-phenoxy-5-(pyridine-4-ylthio)pyridine-2-yl)thiazol-2-amine;
N-(3-phenoxy-5-(pyridine-4-ylthio)pyridine-2-yl)thiazol-2-amine;
4-isopropyl-N-(3-phenoxy-5-(pyridine-4-ylthio)pyridine-2-yl)thiazol-2-amine;
N-(5-bromo-3-phenoxypyridine-2-yl)-4-(piperidine-4-yl)thiazol-2-amine;
N-(5-bromo-3-phenoxypyridine-2-yl)-4-(1-methylpiperidin-4-yl)thiazol-2-amine;
2-(4-(2-(5-bromo-3-phenoxypyridine-2-ylamino)thiazol-4-yl)piperidine-1-yl)Etalon;
1-(4-(2-(5-bromo-3-f is oxypyridine-2-ylamino)thiazol-4-yl)piperidine-1-yl)Etalon;
N-(5-bromo-3-phenoxypyridine-2-yl)-4-penetrtion-2-amine;
N-(5-bromo-3-(4-pertenece)pyridine-2-yl)-4-penetrtion-2-amine;
N-(5-bromo-3-(phenylthio)pyridine-2-yl)-4-methylthiazole-2-amine;
N-(5-bromo-3-(phenylthio)pyridine-2-yl)thiazolo[5,4-b]pyridine-2-amine;
N-(5-bromo-3-(phenylthio)pyridine-2-yl)-3-methyl-1,2,4-oxadiazol-5-amine;
N-(5-bromo-3-phenoxypyridine-2-yl)-3-(tetrahydrofuran-2-yl)-1,2,4-thiadiazole-5-amine;
N-(5-bromo-3-phenoxypyridine-2-yl)-3-methyl-1,2,4-thiadiazole-5-amine;
N-(5-bromo-3-phenoxypyridine-2-yl)-3-(piperidine-4-yl)-1,2,4-thiadiazole-5-amine;
N-(5-bromo-3-phenoxypyridine-2-yl)-3-isobutyl-1,2,4-thiadiazole-5-amine;
N-(5-bromo-3-(phenylthio)pyridine-2-yl)-3-methyl-1,2,4-thiadiazole-5-amine;
N-(5-bromo-3-(phenylthio)pyridine-2-yl)-3-isopropyl-1,2,4-thiadiazole-5-amine;
N-(5-bromo-3-(4-pertenece)pyridine-2-yl)-3-methyl-1,2,4-thiadiazole-5-amine;
N-(5-bromo-3-(4-pertenece)pyridine-2-yl)-3-isobutyl-1,2,4-thiadiazole-5-amine;
tert-butyl 4-(5-(5-bromo-3-(4-pertenece)pyridine-2-ylamino)-1,2,4-thiadiazole-3-yl)piperidine-1-carboxylate;
tert-butyl 4-((5-(5-bromo-3-(4-pertenece)pyridine-2-ylamino)-1,2,4-thiadiazole-3-yl)methyl)piperidine-1-carboxylate;
4-methyl-N-(3-(phenylthio)-5-((tetrahydro-2H-Piran-4-yl)methyl)pyridin-2-yl)thiazol-2-amine;
N-(5-(2-chloro-5-methoxyphenyl)-3-phenoxypyridine-2-yl)-4-methylthiazole-2-amine;
(R)-4-methyl-N-(5-(5-methyl-6,7-dihydro-5H-cyclopent[d]pyrimidine-4-ylthio)-3-phenoxypyridine-2-yl)thiazol-2-amine;
3-(2-(3-phenoxy-5-(pyridine-4-ylthio)pyridi the-2-ylamino)thiazol-4-yl)propanoic acid;
N-(5-(3,5-dimethylisoxazole[4,5-b]pyridine-7-ylthio)-3-phenoxypyridine-2-yl)-4-methylthiazole-2-amine;
1-(4-(2-(3-phenoxy-5-(thieno[3,2-b]pyridine-7-ylthio)pyridine-2-ylamino)thiazol-4-yl)piperidine-1-yl)Etalon;
1-(4-(5-(5-bromo-3-phenoxypyridine-2-ylamino)-1,2,4-thiadiazole-3-yl)piperidine-1-yl)Etalon;
1-(4-(5-(3-phenoxy-5-(thieno[3,2-b]pyridine-7-ylthio)pyridine-2-ylamino)-1,2,4-thiadiazole-3-yl)piperidine-1-yl)Etalon;
1-(4-(5-(3-(phenylthio)-5-(thieno[3,2-b]pyridine-7-ylthio)pyridine-2-ylamino)-1,2,4-thiadiazole-3-yl)piperidine-1-yl)Etalon;
1-(4-(2-(3-(phenylthio)-5-(pyridine-2-ylthio)pyridine-2-ylamino)thiazol-4-yl)piperidine-1-yl)Etalon;
methyl 4-(2-(3-(phenylthio)-5-(pyridine-2-ylthio)pyridine-2-ylamino)thiazol-4-yl)piperidine-1-carboxylate;
1-(4-(2-(3-(phenylthio)-5-(thieno[3,2-b]pyridine-7-ylthio)pyridine-2-ylamino)thiazol-4-yl)piperidine-1-yl)Etalon;
4-(1-(methylsulphonyl)piperidine-4-yl)-N-(3-(phenylthio)-5-(thieno[3,2-b]pyridine-7-ylthio)pyridine-2-yl)thiazol-2-amine;
2-(dimethylamino)-1-(4-(2-(3-(phenylthio)-5-(thieno[3,2-b]pyridine-7-ylthio)pyridine-2-ylamino)thiazol-4-yl)piperidine-1-yl)Etalon;
1-(4-(5-(3-(4-pertenece)-5-(5-methylpyrazolo[1,5-a]pyrimidine-7-ylthio)pyridine-2-ylamino)-1,2,4-thiadiazole-3-yl)piperidine-1-yl)Etalon;
1-(4-(5-(3-(4-pertenece)-5-(thieno[3,2-b]pyridine-7-ylthio)pyridine-2-ylamino)-1,2,4-thiadiazole-3-yl)piperidine-1-yl)Etalon;
N-(3-(4-pertenece)-5-(thieno[3,2-b]pyridine-7-ylthio)pyridine-2-yl)-3-(1-(methylsulphonyl)piperidine-4-yl)-1,2,4-thiadiazole-5-amine;
2-(dimethylamino)1-(4-(5-(3-(4-pertenece)-5-(thieno[3,2-b]pyridine-7-ylthio)pyridine-2-ylamino)-1,2,4-thiadiazole-3-yl)piperidine-1-yl)Etalon;
3-(phenylthio)-N-(3-(piperidine-4-yl)-1,2,4-thiadiazole-5-yl)-5-(thieno[3,2-b]pyridine-7-ylthio)pyridine-2-amine;
N-(3-(phenylthio)-5-(pyridine-2-ylthio)pyridine-2-yl)-4-(piperidine-4-yl)thiazol-2-amine;
tert-butyl 4-(2-(3-(phenylthio)-5-(thieno[3,2-b]pyridine-7-ylthio)pyridine-2-ylamino)thiazol-4-yl)piperidine-1-carboxylate;
tert-butyl 4-(5-(3-(4-pertenece)-5-(5-methylpyrazolo[1,5-a]pyrimidine-7-ylthio)pyridine-2-ylamino)-1,2,4-thiadiazole-3-yl)piperidine-1-carboxylate;
sodium 4-(6-(4-methylthiazole-2-ylamino)-5-phenoxypyridine-3-ylthio)benzoate;
3-methyl-7-(6-(4-penetrtion-2-ylamino)-5-phenoxypyridine-3-ylthio)thieno[3,2-b]piperidine-6-carboxylic acid;
3-methyl-7-(6-(4-methylthiazole-2-ylamino)-5-phenoxypyridine-3-ylthio)thieno[3,2-b]piperidine-6-carboxylic acid;
N-(5-(6,7-dihydro-5H-pyrrolo[3,4-b]pyridine-4-ylthio)-3-phenoxypyridine-2-yl)-4-methylthiazole-2-amine;
N-(4-methylthiazole-2-yl)-3-phenoxy-5-(5,6,7,8-tetrahydropyrido[4,3-d]pyrimidine-4-ylthio)pyridine-2-amine;
1-(4-((5-(3-(4-pertenece)-5-(thieno[3,2-b]pyridine-7-ylthio)pyridine-2-ylamino)-1,2,4-thiadiazole-3-yl)methyl)piperidine-1-yl)Etalon;
1-(4-(5-(3-(4-pertenece)-5-(3-methylisoxazole[5,4-b]pyridine-4-ylthio)pyridine-2-ylamino)-1,2,4-thiadiazole-3-yl)piperidine-1-yl)Etalon;
2-(dimethylamino)-1-(4-(5-(3-(4-pertenece)-5-(3-methylisoxazole[5,4-b]pyridine-4-ylthio)pyridine-2-ylamino)-1,2,4-thiadiazole-3-yl)piperidine-1-yl)Etalon;
tert-butyl 4-(5-(3-phenoxy-5-(thieno[3,2-b]pyridine-7-ylthio)pyridine-2-ylamino)-1,2,4-thiadiazole--yl)piperidine-1-carboxylate;
N-(5-((3-methoxypyridine-2-yl)methylthio)-3-phenoxypyridine-2-yl)-4-methylthiazole-2-amine;
4-methyl-N-(3-phenoxy-5-(piperidine-4-yl(pyridin-2-yl)methylthio)pyridine-2-yl)thiazol-2-amine;
4-methyl-N-(3-phenoxy-5-(piperidine-4-yl(pyrazin-2-yl)methylthio)pyridine-2-yl)thiazol-2-amine;
4-methyl-N-(3-phenoxy-5-(piperidine-4-yl(pyrimidine-2-yl)methylthio)pyridine-2-yl)thiazol-2-amine;
N-(5-((3-chloropyridin-2-yl)(piperidine-4-yl)methylthio)-3-phenoxypyridine-2-yl)-4-methylthiazole-2-amine;
N-(2-(dimethylamino)ethyl)-3-(2-(4-isobutylthiazole-2-ylamino)-5-(pyrimidine-2-ylthio)pyridine-3-yloxy)benzamide;
2-(4-((6-(4-methylthiazole-2-ylamino)-5-phenoxypyridine-3-ylthio)(pyridin-2-yl)methyl)piperidine-1-yl)ethanol;
4-methyl-N-(5-((1-methylpiperidin-4-yl)(pyridin-2-yl)methylthio)-3-phenoxypyridine-2-yl)thiazol-2-amine;
N-(5-((1-isopropylpiperazine-4-yl)(pyridin-2-yl)methylthio)-3-phenoxypyridine-2-yl)-4-methylthiazole-2-amine;
1-((6-(4-methylthiazole-2-ylamino)-5-phenoxypyridine-3-ylthio)methyl)pyrrolidin-2-he;
ethyl 2-(1-methylpiperidin-4-yl)-2-(6-(4-methylthiazole-2-ylamino)-5-phenoxypyridine-3-ylthio)acetate;
2-(1-methylpiperidin-4-yl)-2-(6-(4-methylthiazole-2-ylamino)-5-phenoxypyridine-3-ylthio)ethanol;
N-ethyl-2-(6-(4-methylthiazole-2-ylamino)-5-phenoxypyridine-3-ylthio)-2-(piperidine-4-yl)ndimethylacetamide;
2-(6-(4-methylthiazole-2-ylamino)-5-phenoxypyridine-3-ylthio)-2-(piperidine-4-yl)-1-(pyrrolidin-1-yl)Etalon;
1-(indolin-1-yl)-2-(6-(4-methylthiazole-2-ylamino)-5-phenoxypyridine-3-ylthio)-2-(Pieper is DIN-4-yl)Etalon;
1-(7-azabicyclo[2.2.1]heptane-7-yl)-2-(6-(4-methylthiazole-2-ylamino)-5-phenoxypyridine-3-ylthio)-2-(piperidine-4-yl)Etalon;
1-(2-methylpiperidin-1-yl)-2-(6-(4-methylthiazole-2-ylamino)-5-phenoxypyridine-3-ylthio)-2-(piperidine-4-yl)Etalon mixture of diastereomers;
2-(4-((6-(4-penetrtion-2-ylamino)-5-phenoxypyridine-3-ylthio)(pyridin-2-yl)methyl)piperidine-1-yl)ethanol;
4-methyl-N-(3-phenoxy-5-(1-(pyridin-2-yl)ethylthio)pyridine-2-yl)thiazol-2-amine;
N-(5-(3-(dimethylamino)-1-phenylpropyl)-3-phenoxypyridine-2-yl)-4-methylthiazole-2-amine;
5-((5-cyclopropyl-1,3,4-thiadiazole-2-yl)methylthio)-N-(4-methylthiazole-2-yl)-3-phenoxypyridine-2-amine;
5-((1,2,4-oxadiazol-3-yl)methylthio)-N-(4-methylthiazole-2-yl)-3-phenoxypyridine-2-amine;
5-((5-methylisoxazol-3-yl)methylthio)-N-(4-methylthiazole-2-yl)-3-phenoxypyridine-2-amine;
5-((3,5-dimethylisoxazol-4-yl)methylthio)-N-(4-methylthiazole-2-yl)-3-phenoxypyridine-2-amine;
5-((5-chloro-1,2,4-thiadiazole-3-yl)methylthio)-N-(4-methylthiazole-2-yl)-3-phenoxypyridine-2-amine;
N-(5-(isoquinoline-1-immedilty)-3-phenoxypyridine-2-yl)-4-methylthiazole-2-amine;
N-(4-((6-(4-methylthiazole-2-ylamino)-5-phenoxypyridine-3-ylthio)methyl)thiazol-2-yl)ndimethylacetamide;
N-(5-((5-cyclopropyl-1,3,4-thiadiazole-2-yl)methylthio)-3-(phenylthio)pyridine-2-yl)-4-methylthiazole-2-amine;
4-methyl-N-(5-((5-methylisoxazol-3-yl)methylthio)-3-(phenylthio)pyridine-2-yl)thiazol-2-amine;
N-(5-((3,5-dimethylisoxazol-4-yl)methylthio)-3-(phenylthio)pyridine-2-yl)-4-methylthiazole-2-amine;
2-(6-(4-metelli the evils-2-ylamino)-5-phenoxypyridine-3-ylthio)-1-(pyrrolidin-1-yl)Etalon;
N-(2-(dimethylamino)ethyl)-N-methyl-2-(6-(4-methylthiazole-2-ylamino)-5-phenoxypyridine-3-ylthio)ndimethylacetamide;
1-(4-methylpiperazin-1-yl)-2-(6-(4-methylthiazole-2-ylamino)-5-phenoxypyridine-3-ylthio)Etalon;
2-(6-(4-methylthiazole-2-ylamino)-5-phenoxypyridine-3-ylthio)-N-(2-(pyrrolidin-1-yl)ethyl)ndimethylacetamide;
{5-[(1,1-dioxo-hexahydro-1λ6-thiopyran-4-yl)-pyridine-2-yl-methylsulfanyl]-3-phenoxy-pyridine-2-yl}-(4-methyl-thiazol-2-yl)-amine;
N-(5-bromo-3-phenoxypyridine-2-yl)-4-(2-(methylthio)ethyl)thiazol-2-amine;
N-(5-bromo-3-phenoxypyridine-2-yl)-4-(2-(methylsulphonyl)ethyl)thiazol-2-amine;
4-methyl-N-(3-phenoxy-5-(1-(piperidine-4-yl)ethylthio)pyridine-2-yl)thiazol-2-amine;
N-(5-(benzyloxy)-3-(phenylthio)pyridine-2-yl)-4-methylthiazole-2-amine;
4-methyl-N-(3-(phenylthio)-5-(2-(piperidine-4-yl)ethyl)pyridin-2-yl)thiazol-2-amine;
2,2-dimethyl-3-(2-(3-phenoxy-5-(thieno[3,2-b]pyridine-7-ylthio)pyridine-2-ylamino)thiazol-4-yl)propanoic acid;
tert-butyl 4-(5-(3-phenoxy-5-(pyridine-2-ylthio)pyridine-2-ylamino)-1,2,4-thiadiazole-3-yl)piperidine-1-carboxylate;
3-isobutyl-N-(3-phenoxy-5-(pyridine-2-ylthio)pyridine-2-yl)-1,2,4-thiadiazole-5-amine;
3-isopropyl-N-(3-phenoxy-5-(pyridine-2-ylthio)pyridine-2-yl)-1,2,4-thiadiazole-5-amine;
N-(3-phenoxy-5-(pyridine-2-ylthio)pyridine-2-yl)-3-(tetrahydrofuran-2-yl)-1,2,4-thiadiazole-5-amine;
N-(3-phenoxy-5-(pyridine-2-ylthio)pyridine-2-yl)-3-(piperidine-4-yl)-1,2,4-thiadiazole-5-amine;
1-(4-(5-(3-phenoxy-5-(pyridine-2-ylthio)pyridine-2-ylamino)-1,2,4-thiadiazole-yl)piperidine-1-yl)Etalon;
2-methoxy-1-(4-(5-(3-phenoxy-5-(pyridine-2-ylthio)pyridine-2-ylamino)-1,2,4-thiadiazole-3-yl)piperidine-1-yl)Etalon;
2-(dimethylamino)-1-(4-(5-(3-phenoxy-5-(pyridine-2-ylthio)pyridine-2-ylamino)-1,2,4-thiadiazole-3-yl)piperidine-1-yl)Etalon;
N,N-dimethyl-4-(5-(3-phenoxy-5-(pyridine-2-ylthio)pyridine-2-ylamino)-1,2,4-thiadiazole-3-yl)piperidine-1-carboxamide;
N,N-dimethyl-4-(5-(3-phenoxy-5-(pyridine-2-ylthio)pyridine-2-ylamino)-1,2,4-thiadiazole-3-yl)piperidine-1-sulfonamide;
2-methyl-1-(4-(5-(3-phenoxy-5-(pyridine-2-ylthio)pyridine-2-ylamino)-1,2,4-thiadiazole-3-yl)piperidine-1-yl)propane-1-he;
3-(1-(methylsulphonyl)piperidine-4-yl)-N-(3-phenoxy-5-(pyridine-2-ylthio)pyridine-2-yl)-1,2,4-thiadiazole-5-amine;
2-oxo-2-(4-(5-(3-phenoxy-5-(pyridine-2-ylthio)pyridine-2-ylamino)-1,2,4-thiadiazole-3-yl)piperidine-1-yl)ethyl acetate;
4-(5-(3-phenoxy-5-(pyridine-2-ylthio)pyridine-2-ylamino)-1,2,4-thiadiazole-3-yl)piperidine-1-carboxamide;
2-hydroxy-1-(4-(5-(3-phenoxy-5-(pyridine-2-ylthio)pyridine-2-ylamino)-1,2,4-thiadiazole-3-yl)piperidine-1-yl)Etalon;
tert-butyl 2-oxo-2-(4-(5-(3-phenoxy-5-(pyridine-2-ylthio)pyridine-2-ylamino)-1,2,4-thiadiazole-3-yl)piperidine-1-yl)ethylcarbamate;
(R)-2-hydroxy-1-(4-(5-(3-phenoxy-5-(pyridine-2-ylthio)pyridine-2-ylamino)-1,2,4-thiadiazole-3-yl)piperidine-1-yl)propane-1-he;
2-methyl-1-(4-(5-(3-phenoxy-5-(pyridine-2-ylthio)pyridine-2-ylamino)-1,2,4-thiadiazole-3-yl)piperidine-1-yl)propane-1-he;
2-amino-1-(4-(5-(3-phenoxy-5-(pyridine-2-ylthio)pyridine-2-ylamino)-1,2,4-thiadiazole-3-yl)p is peridin-1-yl)Etalon;
2-(4-(5-(3-phenoxy-5-(pyridine-2-ylthio)pyridine-2-ylamino)-1,2,4-thiadiazole-3-yl)piperidine-1-yl)ethanol;
4-(5-(3-phenoxy-5-(pyridine-2-ylthio)pyridine-2-ylamino)-1,2,4-thiadiazole-3-yl)piperidine-1-sulfonamide;
3-(1-(2-aminomethanesulfonic)piperidine-4-yl)-N-(3-phenoxy-5-(pyridine-2-ylthio)pyridine-2-yl)-1,2,4-thiadiazole-5-amine;
tert-butyl 3-methyl-4-(2-(3-phenoxy-5-(pyridine-2-ylthio)pyridine-2-ylamino)thiazol-4-yl)piperidine-1-carboxylate;
1-(3-methyl-4-(2-(3-phenoxy-5-(pyridine-2-ylthio)pyridine-2-ylamino)thiazol-4-yl)piperidine-1-yl)Etalon;
1-(4-(2-(3-phenoxy-5-(pyridine-2-ylthio)pyridine-2-ylamino)thiazol-4-yl)piperidine-1-yl)Etalon;
N-(5-bromo-3-phenoxypyridine-2-yl)thiazolo[5,4-b]pyridine-2-amine;
methyl 3-(5-phenoxy-6-(thiazolo[5,4-b]pyridine-2-ylamino)pyridine-3-ylthio)propanoate;
N-(3-phenoxy-5-(pyridine-4-ylthio)pyridine-2-yl)thiazolo[5,4-b]pyridine-2-amine;
4-(2-(thiazolo[5,4-b]pyridine-2-ylamino)pyridine-3-ylthio)benzonitrile;
2-(2-(thiazolo[5,4-b]pyridine-2-ylamino)pyridine-3-ylthio)benzonitrile;
4-(5-phenoxy-6-(thiazolo[5,4-b]pyridine-2-ylamino)pyridine-3-ylthio)benzonitrile;
N-(3-phenoxy-5-(pyrimidine-2-ylthio)pyridine-2-yl)thiazolo[5,4-b]pyridine-2-amine;
N-(3-phenoxy-5-(thieno[3,2-b]pyridine-7-ylthio)pyridine-2-yl)thiazolo[5,4-b]pyridine-2-amine;
N-(3-(thieno[3,2-b]pyridine-7-ylthio)pyridine-2-yl)thiazolo[5,4-b]pyridine-2-amine;
N-(5-bromo-3-phenoxypyridine-2-yl)thiazolo[5,4-N]pyridine-2-amine;
N-(5-bromo-3-(4-pertenece)pyridine-2-yl)thiazolo[5,4-b]pyridine-2-amine;
4-(bromo-2-(thiazolo[5,4-b]pyridine-2-ylamino)pyridine-3-yloxy)benzonitrile;
4-(5-bromo-2-(4-methylthiazole-2-ylamino)pyridine-3-yloxy)benzonitrile;
methyl 4-(5-bromo-2-(thiazolo[5,4-b]pyridine-2-ylamino)pyridine-3-ylthio)benzoate;
4-(5-bromo-2-(thiazolo[5,4-b]pyridine-2-ylamino)pyridine-3-yloxy)-2-(trifluoromethyl)benzonitrile;
4-(5-bromo-2-(thiazolo[5,4-b]pyridine-2-ylamino)pyridine-3-ylthio)benzoic acid;
ethyl 2-(5-bromo-2-(thiazolo[5,4-b]pyridine-2-ylamino)pyridine-3-ylthio)-5-perbenzoate;
4-(5-bromo-2-(thiazolo[5,4-b]pyridine-2-ylamino)pyridine-3-yloxy)-3-methylbenzonitrile;
4-(5-bromo-2-(thiazolo[5,4-b]pyridine-2-ylamino)pyridine-3-yloxy)-3-perbenzoate;
4-(5-bromo-2-(thiazolo[5,4-b]pyridine-2-ylamino)pyridine-3-yloxy)-3-chlorobenzonitrile;
3-(5-bromo-2-(thiazolo[5,4-b]pyridine-2-ylamino)pyridine-3-yloxy)-4-chlorobenzonitrile;
3-methyl-N-(5-(3-methylisoxazole[5,4-b]pyridine-4-ylthio)-3-phenoxypropan-2-yl)-1,2,4-thiadiazole-5-amine;
N-(5-bromo-3-(4-pertenece)pyrazin-2-yl)-3-methyl-1,2,4-thiadiazole-5-amine;
3-(2-(5-bromo-3-phenoxypyridine-2-ylamino)thiazol-4-yl)propanoic acid;
3-(2-(5-bromo-3-phenoxypyridine-2-ylamino)thiazol-4-yl)-2,2-dimethylpropanoyl acid;
3-(2-(5-bromo-3-phenoxypyridine-2-ylamino)thiazol-4-yl)-3-methylbutanoyl acid;
2-(2-(5-bromo-3-phenoxypyridine-2-ylamino)thiazol-4-yl)-2-methylpropanoyl acid;
2-(2-(5-bromo-3-phenoxypyridine-2-ylamino)thiazol-4-yl)acetic acid;
3-(2-(5-bromo-3-phenoxypyridine-2-ylamino)thiazol-4-yl)propanenitrile;
4-benzyl-N-(5-bromo-3-phenoxypyridine-2-yl)t the azole-2-amine;
N-(5-bromo-3-phenoxypyridine-2-yl)-4-(chloromethyl)thiazol-2-amine;
3-(2-(5-bromo-3-phenoxypyridine-2-ylamino)thiazol-4-yl)-N-methylpropanamide;
3-(2-(5-bromo-3-phenoxypyridine-2-ylamino)thiazol-4-yl)-N,N-dimethylpropanamide;
3-(2-(5-bromo-3-phenoxypyridine-2-ylamino)thiazol-4-yl)-1-(pyrrolidin-1-yl)propane-1-he;
3-(2-(5-bromo-3-phenoxypyridine-2-ylamino)thiazol-4-yl)-N-(2-methoxyethyl)propanamide;
3-(2-(5-bromo-3-phenoxypyridine-2-ylamino)thiazol-4-yl)-N-(2-hydroxyethyl)propanamide;
3-(2-(5-bromo-3-phenoxypyridine-2-ylamino)thiazol-4-yl)-N-(2-(dimethylamino)ethyl)propanamide;
2-(2-(5-bromo-3-phenoxypyridine-2-ylamino)thiazol-4-yl)-N-methylacetamide;
2-(2-(5-bromo-3-phenoxypyridine-2-ylamino)thiazol-4-yl)-N,N-dimethylacetamide;
2-(2-(5-bromo-3-phenoxypyridine-2-ylamino)thiazol-4-yl)-1-(pyrrolidin-1-yl)Etalon;
2-(2-(5-bromo-3-phenoxypyridine-2-ylamino)thiazol-4-yl)-N-(2-methoxyethyl)ndimethylacetamide;
2-(2-(5-bromo-3-phenoxypyridine-2-ylamino)thiazol-4-yl)-N-(2-hydroxyethyl)ndimethylacetamide;
2-(2-(5-bromo-3-phenoxypyridine-2-ylamino)thiazol-4-yl)-N-(2-(dimethylamino)ethyl)ndimethylacetamide;
3-(2-(5-bromo-3-phenoxypyridine-2-ylamino)thiazol-4-yl)-N-(2-hydroxyethyl)-2,2-dimethylpropanamide;
N-(5-bromo-3-phenoxypyridine-2-yl)-4-(2-(5-methyl-1,3,4-oxadiazol-2-yl)ethyl)thiazol-2-amine;
N-(5-bromo-3-phenoxypyridine-2-yl)-4-((5-methyl-1,3,4-oxadiazol-2-yl)methyl)thiazol-2-amine;
N-(5-bromo-3-phenoxypyridine-2-yl)-4-(2-(5-isopropyl-1,3,4-oxadiazol-2-yl)ethyl)thiazol-2-amine;
N-(5-bromo-3-phenoxypoly the Jn-2-yl)-4-(2-(3-methyl-1,2,4-oxadiazol-5-yl)ethyl)thiazol-2-amine;
N-(5-bromo-3-phenoxypyridine-2-yl)-4-((3-methyl-1,2,4-oxadiazol-5-yl)methyl)thiazol-2-amine;
N-(5-bromo-3-phenoxypyridine-2-yl)-4-(2-(5-methoxazole-2-yl)ethyl)thiazol-2-amine;
N-(5-bromo-3-phenoxypyridine-2-yl)-4-((5-methoxazole-2-yl)methyl)thiazol-2-amine;
4-(2-(1H-tetrazol-5-yl)ethyl)-N-(5-bromo-3-phenoxypyridine-2-yl)thiazol-2-amine;
N-(5-bromo-3-phenoxypyridine-2-yl)-4-(phenoxymethyl)thiazol-2-amine;
N-(5-bromo-3-phenoxypyridine-2-yl)-4-((phenylamino)methyl)thiazol-2-amine;
N-((2-(5-bromo-3-phenoxypyridine-2-ylamino)thiazol-4-yl)methyl)-5-methyl-1,3,4-oxadiazol-2-amine;
N-(5-bromo-3-phenoxypyridine-2-yl)-4-(pyrrolidin-1-ylmethyl)thiazol-2-amine;
5-bromo-3-phenoxy-N-(4-(phenylthiomethyl)thiazol-2-yl)pyridine-2-amine;
5-(2-(2-(5-bromo-3-phenoxypyridine-2-ylamino)thiazol-4-yl)ethyl)-1,3,4-oxadiazol-2-ol;
N-(5-bromo-3-phenoxypyridine-2-yl)-4-(2-(5-methyl-1,2,4-oxadiazol-3-yl)ethyl)thiazol-2-amine;
N-(5-bromo-3-(phenylthio)pyridine-2-yl)-4-(2-(5-methyl-1,3,4-oxadiazol-2-yl)ethyl)thiazol-2-amine;
N-(5-bromo-3-(4-(trifluoromethyl)phenoxy)pyridine-2-yl)-3-(tetrahydrofuran-2-yl)-1,2,4-thiadiazole-5-amine;
N-(5-(pyridine-2-ylthio)-3-(4-(trifluoromethyl)phenoxy)pyridine-2-yl)-3-(tetrahydrofuran-2-yl)-1,2,4-thiadiazole-5-amine;
N-(4-(2-(5-methoxazole-2-yl)ethyl)thiazol-2-yl)-3-phenoxy-5-(thieno[3,2-b]pyridine-7-ylthio)pyridine-2-amine;
4-(2-(5-methoxazole-2-yl)ethyl)-N-(3-phenoxy-5-(piperidine-4-immedilty)pyridine-2-yl)thiazol-2-amine;
N-(5-bromo-3-(4-forfinally)pyridine-2-yl)thiazolo[5,4-b]pyridine-2-amine; methyl 3-(5-bromo-2-(thiazolo[5,4-b]pyridine-2-ylamino)pyridine-3-ylthio)benzoate;
N-(3-(1-methyl-1H-imidazol-2-ylthio)pyridine-2-yl)thiazolo[5,4-b]pyridine-2-amine;
5-bromo-3-(4-forfinally)-N-(4-methylthiazole-2-yl)pyridine-2-amine;
methyl 2-(5-bromo-2-(4-methylthiazole-2-ylamino)pyridine-3-ylthio)-1-methyl-1H-imidazole-5-carboxylate;
5-bromo-N-(4-methylthiazole-2-yl)-3-(pyrimidine-2-ylthio)pyridine-2-amine;
3-(5-bromo-2-(thiazolo[5,4-b]pyridine-2-ylamino)pyridine-3-ylthio)benzoic acid;
3-(5-bromo-2-(thiazolo[5,4-b]pyridine-2-ylamino)pyridine-3-ylthio)-N-(2-(dimethylamino)ethyl)benzamide;
(4-(5-bromo-2-(thiazolo[5,4-b]pyridine-2-ylamino)pyridine-3-ylthio)phenyl)(4-methylpiperazin-1-yl)methanon;
4-(5-bromo-2-(thiazolo[5,4-b]pyridine-2-ylamino)pyridine-3-ylthio)-N-(2-(dimethylamino)ethyl)benzamide;
2-(5-bromo-2-(4-methylthiazole-2-ylamino)pyridine-3-ylthio)-N-(2-(dimethylamino)ethyl)-1-methyl-1H-imidazol-5-carboxamide;
3-(5-bromo-2-(4-methyl-thiazol-2-ylamino)pyridine-3-ylthio)-N-(2-(dimethylamino)ethyl)benzamide;
(2-(5-bromo-2-(4-methylthiazole-2-ylamino)pyridine-3-ylthio)-1-methyl-1H-imidazol-5-yl)methanol;
3-(5-bromo-2-(4-methylthiazole-2-ylamino)pyridine-3-ylthio)benzoic acid;
3-(5-bromo-2-(4-methylthiazole-2-ylamino)pyridine-3-ylthio)benzamide;
3-(5-bromo-2-(4-methylthiazole-2-ylamino)pyridine-3-ylthio)benzonitrile;
4-methyl-N-(3-(2-(trifluoromethyl)phenylthio)pyridine-2-yl)thiazol-2-amine;
4-methyl-N-(3-(m-tolylthio)pyridine-2-yl)thiazol-2-amine;
3-(2-(4-methylthiazole-2-ylamino)pyridine-3-yl) - Rev. IO)phenol;
N-(3-(2-forfinally)-5-(phenylthio)pyridine-2-yl)-4-methylthiazole-2-amine;
N-(3-(2-bromo-5-morpholinoethoxy)pyridine-2-yl)-4-methylthiazole-2-amine;
methyl 3-(2-(5-bromo-3-phenoxypyridine-2-ylamino)thiazol-4-yl)-2-methoxy-2-methylpropanoate;
3-(2-(5-bromo-3-phenoxypyridine-2-ylamino)thiazol-4-yl)-2-methoxy-2-methylpropanoyl acid;
3-(2-(5-bromo-3-phenoxypyridine-2-ylamino)thiazol-4-yl)-2-methoxy-2-methyl-1-(pyrrolidin-1-yl)propane-1-he;
3-(2-(5-bromo-3-phenoxypyridine-2-ylamino)thiazol-4-yl)-N-(2-hydroxyethyl)-2-methoxy-2-methylpropanamide;
N'-(3-(2-(5-bromo-3-phenoxypyridine-2-ylamino)thiazol-4-yl)-2-methoxy-2-methylpropanoyl)-N,N-dimethylformamidine;
3-(2-(5-bromo-3-(phenylthio)pyridine-2-ylamino)thiazol-4-yl)-2-methoxy-2-methylpropanoyl acid;
3-(2-(5-bromo-3-(phenylthio)pyridine-2-ylamino)thiazol-4-yl)-N-(2-hydroxyethyl)-2-methoxy-2-methylpropanamide;
3-(2-(5-bromo-3-(phenylthio)pyridine-2-ylamino)thiazol-4-yl)-2-methoxy-N-(2-methoxyethyl)-2-methylpropanamide;
3-(2-(5-bromo-3-(phenylthio)pyridine-2-ylamino)thiazol-4-yl)-N-(2-hydroxyethyl)-2-methoxy-N,2-dimethylpropanamide;
3-(2-(5-bromo-3-(phenylthio)pyridine-2-ylamino)thiazol-4-yl)-1-((R)-3-hydroxypyrrolidine-1-yl)-2-methoxy-2-methylpropan-1-he;
1-((2-(5-bromo-3-phenoxypyridine-2-ylamino)thiazol-4-yl)methyl)pyrrolidin-2-he;
3-((2-(5-bromo-3-(phenylthio)pyridine-2-ylamino)thiazol-4-yl)methyl)-1-methylpyrrolidine-2-he;
3-((2-(5-bromo-3-phenoxypyridine-2-ylamino)thiazol-4-yl)methyl)-1-methylpyrrolidine-2He;
3-((2-(5-bromo-3-phenoxypyridine-2-ylamino)thiazol-4-yl)methyl)pyrrolidin-2-he;
3-((2-(5-bromo-3-(phenylthio)pyridine-2-ylamino)thiazol-4-yl)methyl)pyrrolidin-2-he;
4-amino-2-((2-(5-bromo-3-phenoxypyridine-2-ylamino)thiazol-4-yl)methyl)butane acid;
1-(4-(2-(5-bromo-3-(phenylthio)pyridine-2-ylamino)thiazol-4-yl)piperidine-1-yl)Etalon;
2-(dimethylamino)-1-(4-(5-(3-(4-pertenece)-5-(thieno[3,2-b]pyridine-7-ylthio)pyridine-2-ylamino)-1,2,4-thiadiazole-3-yl)piperidine-1-yl)Etalon;
1-(4-((5-(3-(4-pertenece)-5-(thieno[3,2-b]pyridine-7-ylthio)pyridine-2-ylamino)-1,2,4-thiadiazole-3-yl)methyl)piperidine-1-yl)Etalon;
1-(4-(5-(3-(4-pertenece)-5-(3-methylisoxazole[5,4-b]pyridine-4-ylthio)pyridine-2-ylamino)-1,2,4-thiadiazole-3-yl)piperidine-1-yl)Etalon;
2-(dimethylamino)-1-(4-(5-(3-(4-pertenece)-5-(3-methylisoxazole[5,4-b]pyridine-4-ylthio)pyridine-2-ylamino)-1,2,4-thiadiazole-3-yl)piperidine-1-yl)Etalon;
5-(3-bromophenoxy)-3-(3-methoxybenzylthio)-N-(3-(tetrahydrofuran-2-yl)-1,2,4-thiadiazole-5-yl)pyridin-2-amine;
3-(3-methoxybenzylthio)-5-phenoxy-N-(3-(tetrahydrofuran-2-yl)-1,2,4-thiadiazole-5-yl)pyridin-2-amine;
1-(3-(5-(3-methoxyphenyl)-6-(3-(tetrahydrofuran-2-yl)-1,2,4-thiadiazole-5-ylamino)pyridine-3-yloxy)phenyl)ethanol;
3-(2-bromo-4-pertenece)-5-(3-methoxybenzylthio)-N-(4-(piperidine-4-yl)thiazol-2-yl)pyridine-2-amine;
4-(2-(3-(4-pertenece)-5-(3-methoxyphenyl)pyridine-2-ylamino)thiazol-4-yl)piperidine-1-carboxylate triptorelin;
1-(4-(2-(3-(4-fluoro-2-methylphenoxy)-5-(methoxyphenyl)pyridine-2-ylamino)thiazol-4-yl)piperidine-1-yl)Etalon;
1-(4-(2-(3-(4-pertenece)-5-(3-methoxyphenyl)pyridine-2-ylamino)thiazol-4-yl)piperidine-1-yl)Etalon;
1-(4-(2-(3-(2-bromo-4-pertenece)-5-(3-methoxyphenyl)pyridine-2-ylamino)thiazol-4-yl)piperidine-1-yl)Etalon;
1-(4-(2-(3-(2-bromo-4-pertenece)-5-(3-methoxyphenyl)pyridine-2-ylamino)thiazol-4-yl)piperidine-1-yl)-2-(dimethylamino)Etalon;
1-(4-(2-(5-(thieno[3,2-b]pyridine-7-ylthio)-3-(4-(trifluoromethyl)phenoxy)pyridine-2-ylamino)thiazol-4-yl)piperidine-1-yl)Etalon;
1-(4-(2-(5-(thieno[3,2-b]pyridine-7-ylthio)-3-(2-(trifluoromethyl)phenoxy)pyridine-2-ylamino)thiazol-4-yl)piperidine-1-yl)Etalon;
1-(4-(2-(5-(2-methylthieno[3,2-b]pyridine-7-ylthio)-3-phenoxypyridine-2-ylamino)thiazol-4-yl)piperidine-1-yl)Etalon;
1-(4-(2-(5-(4-methoxypyridine-2-ylthio)-3-phenoxypyridine-2-ylamino)thiazol-4-yl)piperidine-1-yl)Etalon;
4-(6-(4-(1-acetylpiperidine-4-yl)thiazol-2-ylamino)-5-phenoxypyridine-3-ylthio)benzonitrile;
4-(6-(4-(1-acetylpiperidine-4-yl)thiazol-2-ylamino)-5-phenoxypyridine-3-ylthio)-3-(trifluoromethyl)benzonitrile;
4-(6-(4-(1-acetylpiperidine-4-yl)thiazol-2-ylamino)-5-phenoxypyridine-3-ylthio)-2-(trifluoromethyl)benzonitrile;
6-(6-(4-(1-acetylpiperidine-4-yl)thiazol-2-ylamino)-5-phenoxypyridine-3-ylthio)nicotinamide;
5-(6-(4-(1-acetylpiperidine-4-yl)thiazol-2-ylamino)-5-phenoxypyridine-3-ylthio)-3-methoxyvaleronitrile;
ethyl 6-(6-(4-(1-acetylpiperidine-4-yl)thiazol-2-ylamino)-5-phenoxypyridine-3-ylthio)picolinate;
1-(4-(2-(3-phenoxy-5-(6-(trifluoromethyl)PI is one-3-ylthio)pyridine-2-ylamino)thiazol-4-yl)piperidine-1-yl)Etalon;
1-(4-(2-(5-(6-bratiano[3,2-b]pyridine-7-ylthio)-3-phenoxypyridine-2-ylamino)thiazol-4-yl)piperidine-1-yl)Etalon;
1-(4-(5-(5-(thieno[3,2-b]pyridine-7-ylthio)-3-(2-(trifluoromethyl)phenoxy)pyridine-2-ylamino)-1,2,4-thiadiazole-3-yl)piperidine-1-yl)Etalon;
tert-butyl 4-(2-(3-(4-pertenece)-5-(thieno[3,2-b]pyridine-7-ylthio)pyridine-2-ylamino)thiazol-4-yl)piperidine-1-carboxylate;
N-(3-(4-pertenece)-5-(thieno[3,2-b]pyridine-7-ylthio)pyridine-2-yl)-4-(piperidine-4-yl)thiazol-2-amine;
1-(4-(2-(3-(4-pertenece)-5-(thieno[3,2-b]pyridine-7-ylthio)pyridine-2-ylamino)thiazol-4-yl)piperidine-1-yl)Etalon;
2-(4-(2-(3-(4-pertenece)-5-(thieno[3,2-b]pyridine-7-ylthio)pyridine-2-ylamino)thiazol-4-yl)piperidine-1-yl)-2-oxoethyl acetate;
isopropyl 4-(2-(3-(4-pertenece)-5-(thieno[3,2-b]pyridine-7-ylthio)pyridine-2-ylamino)thiazol-4-yl)piperidine-1-carboxylate;
2-(dimethylamino)-1-(4-(2-(3-(4-pertenece)-5-(thieno[3,2-b]pyridine-7-ylthio)pyridine-2-ylamino)thiazol-4-yl)piperidine-1-yl)Etalon;
N-(3-(4-pertenece)-5-(thieno[3,2-b]pyridine-7-ylthio)pyridine-2-yl)-4-(1-(methylsulphonyl)piperidine-4-yl)thiazol-2-amine;
N-(1-(4-(2-(3-(4-pertenece)-5-(thieno[3,2-b]pyridine-7-ylthio)pyridine-2-ylamino)thiazol-4-yl)piperidine-1-yl)-1-oxoprop-2-yl)ndimethylacetamide;
N-(2-(4-(2-(3-(4-pertenece)-5-(thieno[3,2-b]pyridine-7-ylthio)pyridine-2-ylamino)thiazol-4-yl)piperidine-1-yl)-2-oxoethyl)ndimethylacetamide;
4-(1-(2-aminomethanesulfonic)piperidine-4-yl)-N-(3-(4-pertenece)-5-(thieno[3,2-b]pyridine-7-ylthio)pyridine-2-yl)thiazol-2-amine;
4(2-(3-(4-pertenece)-5-(thieno[3,2-b]pyridine-7-ylthio)pyridine-2-ylamino)thiazol-4-yl)piperidine-1-sulfonamide 2,2,2-triptorelin;
4-(2-(3-(4-pertenece)-5-(thieno[3,2-b]pyridine-7-ylthio)pyridine-2-ylamino)thiazol-4-yl)piperidine-1-carboxamide;
tert-butyl 4-(2-(3-(4-pertenece)-5-(3-methylisoxazole[5,4-b]pyridine-4-ylthio)pyridine-2-ylamino)thiazol-4-yl)piperidine-1-carboxylate;
N-(3-(4-pertenece)-5-(3-methylisoxazole[5,4-b]pyridine-4-ylthio)pyridine-2-yl)-4-(piperidine-4-yl)thiazol-2-amine;
1-(4-(2-(3-(4-pertenece)-5-(3-methylisoxazole[5,4-b]pyridine-4-ylthio)pyridine-2-ylamino)thiazol-4-yl)piperidine-1-yl)Etalon;
2-(dimethylamino)-1-(4-(2-(3-(4-pertenece)-5-(3-methylisoxazole[5,4-b]pyridine-4-ylthio)pyridine-2-ylamino)thiazol-4-yl)piperidine-1-yl)Etalon;
methyl 4-(5-(3-phenoxy-5-(pyridine-2-ylthio)pyridine-2-ylamino)-1,2,4-thiadiazole-3-yl)piperidine-1-carboxylate;
1-(4-(2-(5-(3-methylthieno[3,2-b]pyridine-7-ylthio)-3-phenoxypyridine-2-ylamino)thiazol-4-yl)piperidine-1-yl)Etalon;
1-(4-(2-(5-(5-chlorothieno[3,2-b]pyridine-7-ylthio)-3-phenoxypyridine-2-ylamino)thiazol-4-yl)piperidine-1-yl)Etalon;
tert-butyl 4-((2-(5-bromo-3-(4-pertenece)pyridine-2-ylamino)thiazol-4-yl)methyl)-3-oxopiperidine-1-carboxylate;
1-((2-(5-bromo-3-(4-pertenece)pyridine-2-ylamino)thiazol-4-yl)methyl)piperazine-2-he;
1-(4-(2-(3-phenoxy-5-(thieno[2,3-b]pyrimidine-4-ylthio)pyridine-2-ylamino)thiazol-4-yl)piperidine-1-yl)Etalon;
tert-butyl 4-((2-(5-bromo-3-phenoxypyridine-2-ylamino)thiazol-4-yl)methyl)piperidine-1-carboxylate;
tert-butyl 3-(2-(5-bromo-3-phenoxypyridine-2-ylamino)thiazol-4-yl)piperidine-1-carboxy is at;
tert-butyl 3-(2-(5-bromo-3-phenoxypyridine-2-ylamino)thiazol-4-yl)pyrrolidin-1-carboxylate;
tert-butyl 4-(2-(5-bromo-3-(4-cianfrocca)pyridine-2-ylamino)thiazol-4-yl)piperidine-1-carboxylate;
tert-butyl 3-(5-(5-bromo-3-phenoxypyridine-2-ylamino)-1,2,4-thiadiazole-3-yl)pyrrolidin-1-carboxylate;
tert-butyl 4-((2-(5-(3-methoxy-3-oxopropyl)-3-phenoxypyridine-2-ylamino)thiazol-4-yl)methyl)piperidine-1-carboxylate;
tert-butyl 4-(2-(3-(4-cianfrocca)-5-(3-methoxy-3-oxopropyl)pyridine-2-ylamino)thiazol-4-yl)piperidine-1-carboxylate;
tert-butyl 3-(5-(5-(3-methoxy-3-oxopropyl)-3-phenoxypyridine-2-ylamino)-1,2,4-thiadiazole-3-yl)pyrrolidin-1-carboxylate;
tert-butyl 3-(2-(5-(3-methoxy-3-oxopropyl)-3-phenoxypyridine-2-ylamino)thiazol-4-yl)piperidine-1-carboxylate;
tert-butyl 3-(2-(5-(3-methoxy-3-oxopropyl)-3-phenoxypyridine-2-ylamino)thiazol-4-yl)pyrrolidin-1-carboxylate;
tert-butyl 4-{2-[3-phenoxy-5-(thieno[3,2-b]pyridine-7-ylthio)pyridine-2-ylamino]thiazole-4-ylmethyl}piperidine-1-carboxylate;
tert-butyl 4-((2-(5-(4-cyanophenyl)-3-phenoxypyridine-2-ylamino)thiazol-4-yl)methyl)piperidine-1-carboxylate;
tert-butyl 3-((2-(3-phenoxy-5-(thieno[3,2-b]pyridine-7-ylthio)pyridine-2-ylamino)thiazol-4-yl)methyl)piperidine-1-carboxylate;
tert-butyl 3-(5-(3-phenoxy-5-(thieno[3,2-b]pyridine-7-ylthio)pyridine-2-ylamino)-1,2,4-thiadiazole-3-yl)pyrrolidin-1-carboxylate;
tert-butyl 3-(2-(3-phenoxy-5-(thieno[3,2-b]pyridine-7-is ltio)pyridine-2-ylamino)thiazol-4-yl)pyrrolidin-1-carboxylate;
tert-butyl 3-(2-(5-(4-cyanophenyl)-3-phenoxypyridine-2-ylamino)thiazol-4-yl)piperidine-1-carboxylate;
tert-butyl 3-(5-(5-(4-cyanophenyl)-3-phenoxypyridine-2-ylamino)-1,2,4-thiadiazole-3-yl)pyrrolidin-1-carboxylate;
N-(3-phenoxy-5-(thieno[3,2-b]pyridine-7-ylthio)pyridine-2-yl)-4-(piperidine-4-ylmethyl)thiazol-2-amine;
N-(3-phenoxy-5-(thieno[3,2-b]pyridine-7-ylthio)pyridine-2-yl)-4-(piperidine-3-yl)thiazol-2-amine;
N-(3-phenoxy-5-(thieno[3,2-b]pyridine-7-ylthio)pyridine-2-yl)-3-(pyrrolidin-3-yl)-1,2,4-thiadiazole-5-amine;
N-(3-phenoxy-5-(thieno[3,2-b]pyridine-7-ylthio)pyridine-2-yl)-4-(pyrrolidin-3-yl)thiazol-2-amine;
4-(5-phenoxy-6-(4-(piperidine-4-ylmethyl)thiazol-2-ylamino)pyridine-3-ylthio)benzonitrile;
4-(5-phenoxy-6-(3-(pyrrolidin-3-yl)-1,2,4-thiadiazole-5-ylamino)pyridine-3-ylthio)benzonitrile;
4-(5-phenoxy-6-(3-(piperidine-3-yl)-1,2,4-thiadiazole-5-ylamino)pyridine-3-ylthio)benzonitrile;
1-(4-((2-(3-phenoxy-5-(thieno[3,2-b]pyridine-7-ylthio)pyridine-2-ylamino)thiazol-4-yl)methyl)piperidine-1-yl)Etalon;
1-(3-(2-(3-phenoxy-5-(thieno[3,2-b]pyridine-7-ylthio)pyridine-2-ylamino)thiazol-4-yl)piperidine-1-yl)Etalon;
1-(3-(5-(3-phenoxy-5-(thieno[3,2-b]pyridine-7-ylthio)pyridine-2-ylamino)-1,2,4-thiadiazole-3-yl)pyrrolidin-1-yl)Etalon;
1-(3-(2-(3-phenoxy-5-(thieno[3,2-b]pyridine-7-ylthio)pyridine-2-ylamino)thiazol-4-yl)pyrrolidin-1-yl)Etalon;
4-(6-(4-(1-acetylpiperidine-3-yl)thiazol-2-ylamino)-5-phenoxypyridine-3-ylthio)benzonitrile;
4-(6-(3-(1-acetylpyrrolidine-3-yl)-1,2,4-thiadiazole-ylamino)-5-phenoxypyridine-3-ylthio)benzonitrile;
4-(6-(4-((1-acetylpiperidine-4-yl)methyl)thiazol-2-ylamino)-5-phenoxypyridine-3-ylthio)benzonitrile; and
1-(4-(2-(5-(2-chloropyridin-4-ylthio)-3-phenoxypyridine-2-ylamino)thiazol-4-yl)piperidine-1-yl)Etalon;
or its pharmaceutically acceptable salt.

14. Pharmaceutical composition having the properties of a glucokinase activator comprising a therapeutically effective amount of a compound according to any one of claims 1 to 13 and a pharmaceutically acceptable diluent or carrier.

15. The compound according to any one of claims 1 to 13, as an activator of glucokinase, for use in therapy.

16. The use of compounds according to any one of claims 1 to 13 for obtaining a medicinal product having the properties of a glucokinase activator.



 

Same patents:

FIELD: chemistry.

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

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

13 cl, 23 ex, 2 tbl

FIELD: chemistry.

SUBSTANCE: invention relates to novel substituted pyrimidine derivatives, having HIV replication inhibiting properties, or pharmaceutically acceptable salts thereof. In formula (1): R1 denotes hydrogen; R2 and R3 independently denote hydrogen; R7 and R8 denote C1-6alkyl; R4 denotes cyano; R9 denotes C1-6alkyl optionally substituted with cyano, C2-6alkenyl substituted with cyano, C2-6alkynyl optionally substituted with cyano; R5 denotes C1-6alkyl optionally substituted with Ar or Het; C2-6alkenyl optionally substituted with Ar or Het; C2-6alkynyl optionally substituted with Ar or Het; C3-7cycloalkyl; Ar; Het; R6 denotes H, Het; Y denotes -OR11, -NR12R13; R11 denotes hydrogen or C1-6alkyl optionally substituted with hydroxy, C1-6alkoxy or pyridyl; R12 denotes hydrogen or C1-6alkyl; R13 denotes hydrogen or C1-6alkyl; or R12 and R13 together with a nitrogen atom, which is substituted by said two substitutes, form a morpholinyl; imidazolyl; X denotes -NR1-; Het denotes 5- or 6-member completely saturated ring, where one or two ring members are heteroatoms, each independently selected from nitrogen and sulphur, and where the rest of the ring members are carbon atoms; and where any member of the heterocycle with a nitrogen heteroatom can optionally be substituted with C1-6alkyl; where the 5- or 6-member ring can optionally be annelated with a benzene or thiophene ring; each aryl independently denotes phenyl or phenyl substituted with one substitute selected from C1-6alkoxy.

EFFECT: high efficiency of using said compounds.

7 cl, 4 ex, 1 tbl

FIELD: medicine.

SUBSTANCE: there are described substituted imidazo[2,1-b]thiazoles of general formula the R1, R1, R3 R4, M1, M2 radical values are presented in the patent claim cl. 1, as well as methods for making them, drug preparations containing these compounds and application of these compounds for making the drug preparations.

EFFECT: higher efficacy.

23 cl, 3 tbl, 25 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to new compounds of formula

wherein: m, n, R0, R1, R2, R3 and R4 have the values presented in clause 1 of the patent claim provided the compound of formula (I) cannot represent N-methyl-1-(phenylsulphonyl)-1H-indole-4-methanamine.

EFFECT: compounds show 5-NT6 receptor antagonist activity that that allows them being used in the pharmaceutical composition.

19 cl, 3 tbl, 192 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel agents for controlling plant fungal diseases, specifically 3,7-dithia-1,5-diazabicyclo[3,3,0]octane as an agent against Bipolaris sorokiniana, Aspergillus fumigates, Aspergillus niger, synthesis of which takes place in a single step using readily available reactants in contrast to multi-step synthesis of existing agents used for controlling fungal diseases of plants and materials.

EFFECT: obtaining novel agents for controlling plant fungal diseases.

1 cl

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: invention refers to (R)-N-(3-amino-propyl)-N-[1-(5-benzyl-3-methyl-4-oxo-4,5-dihydro-isothiazolo[5,4-d]pyrimidin-6-yl)-2-methyl-propyl]-4-methyl-benzamide substantially free from (S)-N-(3-amino-propyl)-N[1-(5-benzyl-3-methyl-4-oxo-4,5-dihydro-isothiazolo[5,4-d]pyrimidin-6-yl)-2-methypropyl]-4-methyl-benzamide, or its pharmaceutically acceptable salt which shows the properties of Eg5 inhibitor.

EFFECT: invention also refers to a pharmaceutical composition containing said compound and its pharmaceutically acceptable salt.

4 cl, 27 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to compounds of general formula

,

where R1 represents CH3; R2 represents halogeno or CN; R3 represents H or CH3; R4 represents H or CH3; n represents 0, 1 or 2; and to their pharmaceutically acceptable salts. Also, the invention refers to a pharmaceutical composition and to application of the compounds of formula (I) in preparing a drug exhibiting antagonist activity in relation to CX3CR1 receptor.

EFFECT: provided the compounds of formula (I) as CX3CR1 receptor antagonists.

20 cl, 1 tbl, 3 dwg, 10 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to compounds of general formula (I) where the bond b represents a double bond; X represents -S-; each Z1 and Z3 independently represents a direct bond, -N(R5) - or - (CH2)q; Z2 represent -C(O)- or -C(S)-; m represents an integer equal to 1; n represents an integer equal to 1; each of q independently represents an integer varying within 1 to 4; R0 represents hydrogen, halogen, hydroxy, unsubstituted C1-C3alkyl or unsubstituted C1-C3alkoxy; R1 is independently selected from a group consisting of halogen, optionally substituted C1-C3alkyl, -R6OR7, -R6N(R7)2, -R6C(O)R7, -R6C(O)OR7, -R6C(O)N(R7)R9N(R7)2, -R6OC(O)R8, -R6C(O)N(R7)2 or -R6OR9N(R7)2; R2 represents hydrogen; R4 is selected from a group consisting of morpholine, isoxazolyl, thiazolyl, oxazolyl, benzisoxazolyl, benzothiazolyl, dioxynyl, dioxolyl, and optionally substituted phenyl. Also, the invention refers to pharmaceutically acceptable salts of the compounds of formula (I) and to a pharmaceutical composition exhibiting antiproliferative activity and containing the compounds of formula (I).

EFFECT: preparing the compounds of formula (I) exhibiting antiproliferative activity.

21 cl, 11 dwg, 5 tbl, 19 ex

Antiviral compound // 2441010

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to new compounds or their pharmaceutically acceptable salts where the compound has formula (I). The compounds have the properties of hepatitis C virus (HCV) replication inhibition and can be used for treating HCV-infection. In formula (I) B represents heterocyclyl selected from thieno, thiazolo, pyrazolo, pyrido and pyrimidogroup with B being optionally substituted by one or more R18, A represents phenyl which is optionally substituted by one or more R18; each W1 and W2 are independently selected from N or C(R33); Z represents -NH-; each R10 and R33 containing of hydrogen; X is selected from a group consisting of -Ls-O-, -Ls-S-; R22 means hydrogen or phenyl optionally substituted by one or more R26 ; Y is selected from a group consisting of -Ls-O-, -Ls-S-; -Ls-C(O)- and -Ls-NH(SO)2-; R50 represents -L1-A1, where L1 represents a bond, and A1 is selected from a group consisting of carbocyclyl where carbocyclyl represents phenyl or C3-C6carbocyclyl, banzimidazolyl and C1-C6alkyl optionally substituted by phenyl where A1 is optionally substituted by one or more R30 ; the substitute values are specified in the patent claim.

EFFECT: preparing the compounds exhibiting the properties of hepatitis C virus replication inhibition.

17 cl, 8 dwg, 255 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to new compounds of general formula 1, or their pharmaceutically acceptable salts showing the properties of incretin secretagogues, preferentially the properties of a bile acid receptor TGR5 agonist. The compounds are applicable for treating metabolic diseases associated with glucose metabolism, such as diabetes, obesity, metabolic syndrome, etc. In formula 1 R1, R2 and R3 independently represent a cyclic system substitute specified in: hydrogen, C1-C3alkyl, halogen, a trifluoromethyl group, C1-C3alkoxy, a cyano group, a trifluoromethoxy group; an amino group substituted by C1-C3alkyl; or two radicals R3, found at carbon neighbours in a benzene ring, together with the benzene ring bound therewith form 3,4-methylene dioxyphenyl; R4 represents hydrogen, C1-C5alkyl, a carboxyl group, C1-C3alkoxycarbonyl or an amide group CONHR5; R5 is an optionally substituted by C1-C3alkyl, C5-C6cycloalkyl optionally substituted by phenyl, benzyl, pyridyl; X and Y represent two hydrogen atoms or an oxygen atom, provided Y=O, then X=2H, provided Y=2H, then X=O or X=Y=2H; the sign (N) shows the possibility of bioisosteric substitution of the benzene ring by the pyridine, pyrimidine, pyridazine, triazine or pyrazine ones.

EFFECT: preparing the pharmaceutical composition and the combined drugs with the use of the compounds of formula 1 or the based pharmaceutical composition and a protein kinase DPP-IV inhibitor specified in Vildagliptin or Sitagliptin, and/or an endogenous bile acid or mied bile acid secretagogues.

53 cl, 7 dwg, 8 ex

FIELD: chemistry.

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

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

13 cl, 23 ex, 2 tbl

Polycyclic compound // 2451685

FIELD: medicine, pharmaceutics.

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

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

7 cl, 392 ex, 12 tbl

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to (R)-N-(3-amino-propyl)-N-[1-(5-benzyl-3-methyl-4-oxo-4,5-dihydro-isothiazolo[5,4-d]pyrimidin-6-yl)-2-methyl-propyl]-4-methyl-benzamide substantially free from (S)-N-(3-amino-propyl)-N[1-(5-benzyl-3-methyl-4-oxo-4,5-dihydro-isothiazolo[5,4-d]pyrimidin-6-yl)-2-methypropyl]-4-methyl-benzamide, or its pharmaceutically acceptable salt which shows the properties of Eg5 inhibitor.

EFFECT: invention also refers to a pharmaceutical composition containing said compound and its pharmaceutically acceptable salt.

4 cl, 27 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a compound of formula (I), and a salt or hydrate thereof:

,

in which R1 denotes a hydrogen atom; R2 denotes a hydrogen atom; R3 and R4 independently denote a hydrogen atom; R5 denotes a hydrogen atom or a fluorine atom; R6 and R7, together with carbon atoms to which they are bonded, form a 5- or 6-member cyclic structure, where the cyclic structure is a partial structure which, together with a pyrrolidine ring, forms a condensed cyclic (bicyclic) structure, the 5- or 6-member cyclic structure can contain an oxygen atom as a ring atom, R5 can be a methylene group which, together with R6, forms a 3-member condensed cyclic structure; and Q is a partial structure of formula (II):

,

in which R8 denotes a 1,2-cis-2-halogencyclopropyl group, a cyclopropyl group or a 6-amino-3,5-difluoropyridin-2-yl group; R9 denotes a hydrogen atom; R10 denotes a hydrogen atom; R11 denotes a hydrogen atom; XI denotes a fluorine or hydrogen atom; A1 denotes a nitrogen or partial structure of formula (III):

,

in which X2 is a methyl group, an ethyl group, a methoxy group or a chlorine atom, or X2 and R8, together with their coupling part of the parent skeleton, form a cyclic structure, such that Q denotes a partial structure of formula , in which Y0 denotes a methyl group or a pre-methyl group, and X1, R9, R10, R11 assume values given above. The invention also describes a medicinal agent based on said compound, having antibacterial activity, an antibacterial agent and a therapeutic agent for treating infections.

EFFECT: novel compounds are obtained and described, which have strong antibacterial activity not only on gram-negative bacteria, but gram-positive cocci as well, which have low sensitivity to quinolone antibacterial agents, and which demonstrate high safety and excellent pharmacokinetic properties.

18 cl, 61 ex

FIELD: pharmachology.

SUBSTANCE: invention describes new compounds with general formula (I-c) Where R1 is a radical (d-1) or (d-2) (radical values are given in the invention formula) and pharmaceutical composition containing them. The described compounds are the hepatitis C inhibitors and can be used in medicine.

EFFECT: enhanced hepatitis C inhibition.

5 cl, 1 tbl, 19 ex

FIELD: chemistry.

SUBSTANCE: present invention relates to organic chemistry and specifically to novel derivatives of quinolone or one pharmaceutically acceptable salts thereof, solvates thereof or solvates of salts thereof, having general formula I , in which R1 denotes fluorine, R3 denotes halogen, a hydroxy group or a C1-C4-alkoxy group, R4 denotes C1-C6-alkyl or C3-C8-cycloalkyl, where the alkyl can contain 1-3 substitutes, and the substitutes are independently selected from a group comprising halogen or trifluoromethyl, and where the cycloalkyl can contain 1-3 halogen atoms as substitutes, or R3 and R4 together with atoms to which they are bonded form a ring with a group of formula , in which * indicates a site for bonding with a carbon atom, and # indicates a site for bonding with a nitrogen atom, R7 and R8 independently denote halogen, trifluoromethyl, a monofluoromethoxy group, a difluoromethoxy group, a trifluoromethoxy group, C1-C3-alkyl or C1-C3-alkoxy group, and R9 denotes hydrogen, halogen or C1-C3-alkyl, or R8 denotes a trifluoromethoxy group, and R7 and R9 denote hydrogen, R10 denotes a group of formula or , in which * indicates a site for bonding with a carbon atom, R2 is bonded in position 3 or 4 and denotes a hydroxy group, hydroxycarbonyl, aminocarbonyl, C1-C4-alkyl, C1-C4-alkoxycarbonyl, C3-C6-cycloalkylcarbonyl or optionally hydroxy-substituted C1-C6-alkylaminocarbonyl, where the alkyl is substituted with one substitute and the substitute is selected from a group comprising a hydroxy group, hydroxycarbonyl, aminocarbonyl, C1-C4-alkoxycarbonyl and 2-oxopyrrolidin-1-yl, R5 and R6 are independently bonded in positions 3, 4 or 5 and independently denote hydrogen, hydroxy group, methyl or ethyl, and Y denotes a methylene group or an oxygen atom. The invention also relates to methods of producing a compound of formula I, a medicinal agent based on the compound of formula I, use of the compound of formula I and a method of fighting viral infections.

EFFECT: novel substituted quinolone derivatives which are useful in treating viral diseases are obtained.

11 cl, 1 tbl, 69 ex

FIELD: medicine.

SUBSTANCE: invention refers to a compound of formula l where R1 represents CH2CI, CH2F or-C1-2alkyl-R3R4; R3 represents -O-; R4 represents phenyl, where said R4 group is optionally substituted by 0-5 groups J where J represents halogen; R2 represents C6-10aryl; or a group: where Y represents CH, AA2 represents C1-C7alkyl, R8 and R9 represents hydrogen or halogen; or a group: where Y represents CH, AA2 represents C1-C7alkyl, and R6 represents hydrogen, P4 represents -(T)p-R, where T represents -C(O)O-group, R represents C1-C12alkyl, and p is equal to 1; or a group: where A2 represents O, R7 and R8 together with atom whereto attached form a (10-14)members tricyclic unsaturated ring, e.g. carbazole; or a group: where AA2 represents C1-C7alkyl, and R15 represents 2-tert-butylphenyl. The declared compounds are caspase inhibitor prodrugs which under certain conditions can be transformed into biologically active compounds, particularly caspase inhibitors. Also, said invention refers to methods of producing said compounds and to a pharmaceutical composition exhibiting caspase inhibitory action on the basis of the said compounds.

EFFECT: what is produced are new compounds and based pharmaceutical composition which can find application in medicine for treating the diseases associated with inflammatory or degenerative conditions.

13 cl, 5 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a method of producing substituted 4-hydroxy-3-oxo-3,4-dihydro-2H-1,4-benzoxazine-6,7-dicarbonitriles of general formula: where R=H (a); CH3 (b); OCH3 (c); CI (d) which can be used as biologically active substances, fluorescent materials and for synthesis of phthalocyanines. The method involves synthesis of substituted 4-hydroxy-3-oxo-3,4-dihydro-2H-1,4-benzoxazine-6,7-dicarbonitriles through a reaction which takes place in two steps, where at the first step 4-bromo-5-nitrophthalonitrile reacts with sodium salts of substituted 3-phenylpropanoates in molar ratio 1:2, respectively, at temperature 19…25°C for 12-20 hours in dimethyl formamide (DMF) solution, after which the reaction mass is diluted with tenfold excess water with T=0…25°C. The released resinous residue is extracted with dichloromethane, thoroughly washed with water and chromatographed on silica gel. The eluent (solvent) is evaporated. The residue of the intermediate product is filtered and re-crystallised from alcohol. At the second step of the method, tin dichloride solution in concentrated hydrochloric acid is mixed with the solution of the obtained intermediate product in ethyl alcohol in molar ratio 3.5-4.5:1, respectively, at temperature 30...50°C and reaction time of 1-2 hours, after which the reaction mixture is diluted with tenfold excess water with T=0…25°C, and the precipitate is filtered and re-crystallised from alcohol.

EFFECT: obtaining novel heterocyclic dicyano-derivatives of benzoxazines.

1 tbl, 5 ex

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of general formula

,

where R1 is selected from formulae

, and ,

n equals 0; R6 and R7 are independently selected from hydrogen, C1-C6alkyl, cyanoC1-C6alkyl, C3-C6cycloalkylC0-C4alkyl and C6arylC0-C4alkyl; or R6 and R7 together with a carbon atom to which they are bonded form a 6-member heterocycloalkyl with one nitrogen atom; wherein any alkyl in R6 and R7 can optionally contain a methylene group substituted with an O atom; wherein any aryl in R6 and R7 or formed by a combination of R6 and R7 can be optionally substituted with one radical independently selected from: halide, C1-C6alkyl, -XC(O)OR10; where X denotes a bond; R10 is independently selected from C1-C6alkyl; R8 is selected from C5-C9heteroarylC0-C4alkyl containing 2-3 heteroatoms independently selected from N, O and S; wherein any heteroaryl in R8 can be optionally substituted with one radical independently selected from: halide, C1-C6alkyl, C3-C6cycloalkyl; R2 denotes hydrogen; R3 and R4 are independently selected from hydrogen, C1-C6alkyl, C3-C6cycloalkylC0-C4alkyl and C6arylC0-C4alkyl; wherein any alkyl in R3 and R4 can optionally contain a methylene group substituted with a S(O)2 group; R5 is selected from C5-C6heterocycloalkyl with 1-2 heteroatoms selected from N and O, and NR12R13; where R12 and R13 are independently selected from C1-C6alkyl; as well as pharmaceutically acceptable salts and isomers thereof. The invention also relates to use of compounds of formula (I) in preparing a medicinal agent, and to a pharmaceutical composition having cathepsin S inhibiting properties, which contains a therapeutically effective amount of the compound of formula (I) in combination with a pharmaceutically acceptable filler.

EFFECT: obtaining compounds which can be used as cathepsin S inhibitors.

10 cl, 12 dwg, 2 tbl, 9 ex

FIELD: chemistry.

SUBSTANCE: invention relates to new compounds of indole with formula (I) or indole pharmaceutically acceptable salts: where: ring A stands for a benzene or a tiofen ring; R1 stands for a C1-.6 alkyl that may be substituted by one or several groups selected from among -OH, - O-C1-6 alkyl, an amino group that may be substituted by one or two C1-6 alkyls; -O-C1-6 alkyl; a halogen; CN; 5-6-membered cyclic amine; n is equal to 0 - 4 and to 0- 2 if ring A is a benzene or a tiofen ring accordingly; R2 stands for -H, -C1-6 alkyl; R3 stands for H, -C1-6 alkyl that may be substituted by phenyl, C3-6 cycloalkyl; R4 stands for C1-6 alkyl that may be substituted by one or several groups selected from among -OH, -O- C1-6 alkyl, an amino group that may be substituted by one or two C1-6 alkyls and 5-6-membered cyclic amine; C3-6 cycloalkyl, phenyl or-OH; X1 stands for -CH2-, -O-, -S-, -CH(R°)-; X2 stands for -C(RA)(RB)-, -O-; X3 stands for -C(RC)(RD)-; m is equal to 1 - 3; R° stands for -H, or R°, together with R4, form C3-6 alkylene; RA, RB, RC and RD are identical or different and stand for -H, C1-6 alkyl where, in case m is equal to 2 or 3, each RC and R° may be identical or different provided 1- methyl-4a-phenyl-2,3,4,4a,5,9b-hexahydro-1H-indeno [1,2-b] pyridine, 4a-phenyl-2,3,4,4a,5,9b-hexahydro-4aH-indeno [1,2-b] pyridine and 2-(1,2,3,4,5,9b-hexahydro-4aH-indeno [1,2-b] pyridine -4a-yl)-N,N-dimethylethanamine are excluded).

EFFECT: compounds possess antagonistic activity regarding NMDA receptor which enables their usage in pharmaceutical compositions for treatment of Alzheimer disease, vascular dementia, Parkinson disease, chronic depression, attention deficit hyperactivity disorder, migraines etc.

18 cl, 40 tbl, 84 ex

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