Imidazopyridine derivatives
View Patent ↗The present invention relates to compounds of formula (I), wherein R a , R b , R c , R d , R e and R f are as defined in the specification, processes for their preparation, pharmaceutical compositions containing them and their use in the treatment of diseases mediated by phosphatidylinositol-3-kinase (PI3K), mammalian target of rapamycin (mTOR), Signal transducer and activator of transcription 3 (STAT 3), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) or a combination thereof particularly in the treatment of cancer and inflammation.
1. A compound of formula (I)
wherein,
R a , R b and R d are independently selected from hydrogen, hydroxy, halogen, cyano, nitro, —COR 1 , —COOR 1 , —CONH 2 , —NR 1 R 2 , —C 1 -C 8 alkyl, halo-C 1 -C 8 alkyl and —C 1 -C 8 alkoxy;
R c is halogen or heteroaryl;
R e is hydrogen, —C 1 -C 8 alkyl, —C 6 -C 14 aryl or heteroaryl;
Q is —SO 2 , —C(O)NR 1 or —C(S)NR 1 ;
R f is —C 1 -C 8 alkyl, —(CR 1 R 2 ) p —C 3 -C 8 cycloalkyl, —(CR 1 R 2 ) p —C 6 -C 14 aryl, —(CR 1 R 2 ) p heterocyclyl, —(CR 1 R 2 ) p heteroaryl, —C 3 -C 8 cycloalkyl, —C 6 -C 14 aryl, heteroaryl or heterocyclyl;
R 1 and R 2 are independently selected from hydrogen and lower alkyl;
p is independently an integer from 1 to 3;
with the proviso that when Q is —SO 2 , then R c is not halogen;
wherein each of the above alkyl, haloalkyl, alkoxy, cycloalkyl, aryl, heteroaryl and heterocyclyl are unsubstituted or substituted with one or more of the same or different groups selected from halogen, hydroxy, carbonyl, carboxy, ester, ether, acyl, acyloxy, cyano, amino, amide, imino, alkylthio, thioester, sulfonyl, nitro, —C 1 -C 6 alkyl, halo-C 1 -C 6 alkyl, halo-C 1 -C 6 alkoxy, —C 1 -C 6 alkoxy, haloalkoxy, —C 3 -C 8 cycloalkyl, —(CR 1 R 2 ) p -aryl, —C 6 -C 10 aryl, —NHCOMe, —S(O) 2 Me, aryloxy, heterocyclyl and heteroaryl; or
a stereoisomer, tautomer, N-oxide or a pharmaceutically acceptable salt thereof.
2. The compound according to claim 1 , wherein
R a , R b and R d are independently selected from hydrogen and —C 1 -C 8 alkyl;
R c is halogen or heteroaryl;
R e is hydrogen or —C 1 -C 8 alkyl;
Q is —SO 2 , —C(O)NR 1 or —C(S)NR 1 ;
R f is —C 1 -C 8 alkyl, —(CR 1 R 2 ) p —C 3 -C 8 cycloalkyl, —(CR 1 R 2 ) p —C 6 -C 14 aryl, —(CR 1 R 2 ) p -heterocyclyl, —(CR 1 R 2 ) p -heteroaryl, —C 3 -C 8 cycloalkyl, —C 6 -C 14 aryl, heteroaryl or heterocyclyl;
R 1 and R 2 are independently selected from hydrogen and lower alkyl;
p is independently an integer from 1 to 3;
with the proviso that when Q is —SO 2 , then R 1 is not halogen;
wherein each of the above alkyl, cycloalkyl, aryl, heterocyclyl and heteroaryl are unsubstituted or substituted with one or more of the same or different groups selected from halogen, hydroxy, carbonyl, carboxy, ester, ether, acyl, acyloxy, cyano, amino,amide, imino, alkylthio, thioester, sulfonyl, nitro, —C 1 -C 6 alkyl, halo-C 1 -C 6 alkyl, halo-C 1 -C 6 alkoxy, —C 1 -C 6 alkoxy, —C 3 -C 8 cycloalkyl, —(CR 1 R 2 ) p —C 6 -C 10 aryl, —C 6 -C 10 aryl, —NHCOMe, —S(O) 2 Me, aryloxy, heterocyclyl and heteroaryl; or
a stereoisomer, tautomer, N-oxide or a pharmaceutically acceptable salt thereof.
3. The compound according to claim 1 , wherein
R a , R b and R d are independently selected from hydrogen and —C 1 -C 4 alkyl;
R c is halogen or heteroaryl;
R e is hydrogen or —C 1 -C 4 alkyl;
Q is —SO 2 , —C(O)NH or —C(S)NH;
R f is —C 1 -C 8 alkyl, —(CR 1 R 2 ) p —C 6 -C 14 aryl, —(CR 1 R 2 ) p heterocyclyl, —C 3 -C 8 cycloalkyl, —C 6 -C 14 aryl, heterocyclyl, or heteroaryl;
R 1 and R 2 are independently selected from hydrogen and lower alkyl;
p is independently an integer from 1 to 3;
with the proviso that when Q is —SO 2 , then R c is not halogen;
wherein each of the above alkyl, cycloalkyl, aryl, heteroaryl and heterocyclyl are optionally and independently substituted with one or more of the same or different groups selected from halogen, hydroxy, carbonyl, carboxy, ester, ether, acyl, acyloxy, cyano, amino, amide, imino, alkylthio, thioester, sulfonyl, nitro, —C 1 -C 6 alkyl, halo—C 1 -C 6 alkyl, halo-C 1 -C 6 alkoxy, —C 1 -C 6 alkoxy, —NHCOMe, —S(O) 2 Me, aryloxy, heterocyclyl and heteroaryl; or
a stereoisomer, tautomer, N-oxide or a pharmaceutically acceptable salt thereof.
4. The compound according to claim 1 , wherein,
R a , R b and R d are independently selected from hydrogen and —C 1 -C 4 alkyl;
R c is halogen or heteroaryl;
R e is hydrogen or —C 1 -C 4 alkyl;
Q is —C(O)NH or —C(S)NH;
R f is —C 1 -C 8 alkyl, —(CR 1 R 2 ) p —C 6 -C 14 aryl, —(CR 1 R 2 ) p -heterocyclyl, —C 3 -C 8 cycloalkyl, —C 6 -C 14 aryl or heteroaryl;
R 1 and R 2 are independently selected from hydrogen and lower alkyl;
p is independently an integer from 1 to 3;
wherein each of the above alkyl, cycloalkyl, aryl and heteroaryl are optionally and independently substituted with one or more of the same or different groups selected from halogen, hydroxy, cyano, amino, nitro, alkoxy, —C 1 -C 6 alkyl and halo —C 1 -C 6 alkyl; or
a stereoisomer, tautomer, N-oxide or a pharmaceutically acceptable salt thereof.
5. The compound according to claim 1 , wherein
R a , R b and R d are independently selected from hydrogen and —C 1 -C 4 alkyl;
R c is halogen or heteroaryl;
R e is hydrogen or —C 1 -C 4 alkyl;
Q is —C(O)NH or —C(S)NH;
R f is —(CR 1 R 2 ) p -heterocyclyl, —(CR 1 R 2 ) p —C 6 -C 14 aryl or —C 6 -C 14 aryl;
R 1 and R 2 are independently selected from hydrogen and lower alkyl;
p is independently an integer from 1 to 3;
wherein each of the above alkyl, aryl and heteroaryl are optionally and independently substituted with one or more of the same or different groups selected from halogen, hydroxy, cyano, amino, nitro, alkoxy, —C 1 -C 6 alkyl and halo —C 1 -C 6 alkyl; or
a stereoisomer, tautomer, N-oxide or a pharmaceutically acceptable salt thereof.
6. The compound according to claim 1 , wherein
R a , R b and R d are independently selected from hydrogen and —C 1 -C 4 alkyl;
R c is halogen;
R e is hydrogen or —C 1 -C 4 alkyl;
Q is —C(O)NH or —C(S)NH;
R f is —(CR 1 R 2 ) p -heterocyclyl, —(CR 1 R 2 ) p —C 6 -C 14 aryl or —C 6 -C 14 aryl;
R 1 and R 2 are independently selected from hydrogen and lower alkyl;
p is independently an integer from 1 to 3;
wherein each of the above alkyl, aryl and heteroaryl are optionally and independently substituted with one or more of the same or different groups selected from halogen, hydroxy, cyano, amino, nitro, alkoxy, —C 1 -C 6 alkyl and halo-C 1 -C 6 alkyl; or
a stereoisomer, tautomer, N-oxide or a pharmaceutically acceptable salt thereof.
7. The compound according to claim 1 , wherein
R a , R b and R d are independently selected from hydrogen and —C 1 -C 4 alkyl;
R c is heteroaryl;
R e is hydrogen or —C 1 -C 4 alkyl;
Q is —SO 2 , —C(O)NR 1 or —C(S)NR 1 ;
R f is —C 1 -C 8 alkyl, —(CR 1 R 2 ) 1 —C 3 -C 8 cycloalkyl, —(CR 1 R 2 ) p —C 6 -C 14 aryl, —(CR 1 R 2 ) p -heterocyclyl, —(CR 1 R 2 ) p -heteroaryl, —C 3 -C 8 cycloalkyl, —C 6 -C 14 aryl, heteroaryl or heterocyclyl;
R 1 and R 2 are independently selected from hydrogen and lower alkyl;
p is independently an integer from 1 to 3;
wherein each of the above alkyl, cycloalkyl, aryl, heterocyclyl and heteroaryl are optionally and independently substituted with one or more of the same or different groups selected from halogen, hydroxy, carbonyl, carboxy, ester, ether, acyl, acyloxy, cyano, amino, amide, imino, alkylthio, thioester, sulfonyl, nitro, —C 1 -C 6 alkyl, halo—C 1 -C 6 alkyl, —C 1 -C 6 alkoxy, —C 3 -C 8 cycloalkyl, —(CR 1 R 2 ) p —C 6 -C 10 aryl, —C 6 -C 10 aryl, —NHCOMe, —S(O) 2 Me, aryloxy, heterocyclyl and heteroaryl; or
a stereoisomer, tautomer, N-oxide or a pharmaceutically acceptable salt thereof.
8. The compound according to claim 1 , wherein
R a , R b and R d are independently selected from hydrogen and —C 1 -C 4 alkyl;
R c is heteroaryl;
R e is hydrogen or —C 1 -C 4 alkyl;
Q is —SO 2 , —C(O)NH or —C(S)NH;
R f is —C 1 -C 8 alkyl, —(CH 2 ) p —C 6 -C 14 aryl, —(CH 2 ) p -heterocyclyl, —C 3 -C 8 cycloalkyl, —C 6 -C 14 aryl, heteroaryl or heterocyclyl;
p is independently an integer from 1 to 3;
R 1 and R 2 are independently selected from hydrogen and lower alkyl;
wherein each of the above alkyl, aryl, heterocyclyl and heteroaryl are optionally and independently substituted with one or more of the same or different groups selected from halogen, hydroxy, carbonyl, carboxy, ester, ether, acyl, acyloxy, cyano, amino, amide, imino, alkylthio, thioester, sulfonyl, nitro, —C 1 -C 6 alkyl, halo—C 1 -C 6 alkyl, —C 1 -C 6 alkoxy, —C 3 -C 8 cycloalkyl, —(CR 1 R 2 ) p —C 6 -C 10 aryl, —C 6 -C 10 aryl, —NHCOMe, —S(O) 2 Me, aryloxy, heterocyclyl and heteroaryl; or
a stereoisomer, tautomer, N-oxide or a pharmaceutically acceptable salt thereof.
9. The compound according to claim 1 , wherein
R a , R b and R d are independently selected from hydrogen and methyl;
R c is halogen or heteroaryl selected from indolyl, pyrrolyl, pyridyl, pyrimidinyl and quinolinyl wherein each of indolyl, pyrrolyl, pyridyl, pyrimidinyl and quinolinyl is optionally substituted with one or more groups selected from halogen, —C 1 -C 6 -alkyl, —C 1 -C 6 -alkoxy, and halo—C 1 -C 6 -alkyl;
R e is hydrogen or —C 1 -C 4 alkyl;
Q is —SO 2 , —C(O)NH or —C(S)NH;
R f is —C 1 -C 8 alkyl, —(CH 2 ) p —C 6 -C 14 aryl, —(CH 2 ) p -heterocyclyl, —C 3 -C 8 -cycloalkyl, —C 6 -C 14 aryl, heterocyclyl or heteroaryl;
p is independently an integer from 1 to 3;
R 1 and R 2 are independently selected from hydrogen and lower alkyl;
with the proviso that when Q is —SO 2 , then R c is not halogen;
wherein each of the above alkyl, cycloalkyl, aryl, heteroaryl and heterocyclyl are optionally and independently substituted with one or more of the same or different groups selected from halogen, hydroxy, carbonyl, carboxy, ester, ether, acyl, acyloxy, cyano, amino, amide, imino, alkylthio, thioester, sulfonyl, nitro, —C 1 -C 6 alkyl, halo—C 1 -C 6 alkyl, halo—C 1 -C 6 alkoxy, —C 1 -C 6 alkoxy, —C 3 -C 8 cycloalkyl, —(CR 1 R 2 ) p —C 6 -C 10 aryl, —C 6 -C 10 aryl, —NHCOMe, —S(O) 2 Me, aryloxy, heterocyclyl and heteroaryl group;
a stereoisomer, tautomer, N-oxide or a pharmaceutically acceptable salt thereof.
10. The compound according to claim 1 , wherein
R a , R b and R d are independently selected from hydrogen and —C 1 -C 4 alkyl;
R c is heteroaryl;
R e is hydrogen or —C 1 -C 4 alkyl;
Q is —SO 2 ;
R f is —C 1 -C 8 alkyl, —(CR 1 R 2 ) p —C 6 -C 14 aryl, —C 3 -C 8 cycloalkyl, —C 6 -C 14 aryl, heterocyclyl or heteroaryl;
R 1 and R 2 are independently selected from hydrogen and lower alkyl;
p is independently an integer from 1 to 3;
wherein each of the above alkyl, cycloalkyl, aryl, heterocyclyl and heteroaryl are unsubstituted or substituted with one or more of the same or different groups selected from halogen, hydroxy, carbonyl, carboxy, ester, ether, acyl, acyloxy, cyano, amino, amide, imino, alkylthio, thioester, sulfonyl, nitro, —C 1 -C 6 alkyl, halo—C 1 -C 6 alkyl, halo—C 1 -C 6 alkoxy, —C 1 -C 6 alkoxy, —C 3 -C 8 cycloalkyl, —(CR 1 R- 2 ) p —C 6 -C 10 aryl, —C 6 -C 10 aryl, —NHCOMe, —S(O) 2 Me, aryloxy, heterocyclyl and heteroaryl group; or
a stereoisomer, tautomer, N-oxide or a pharmaceutically acceptable salt thereof.
11. The compound according to claim 1 , wherein
R a , R b and R d are independently selected from hydrogen and methyl;
R c is heteroaryl selected from indolyl, pyrrolyl, pyridyl, pyrimidinyl and quinolinyl, wherein each of indolyl, pyrrolyl, pyridyl, pyrimidinyl and quinolinyl is optionally substituted with one or more groups selected from halogen, —C 1 -C 6 -alkyl, —C 1 -C 6 -alkoxy, and halo—C 1 -C 6 -alkyl;
R e is hydrogen or —C 1 -C 4 alkyl;
Q is —SO 2 ;
R f is —(CH 2 ) p —C 6 -C 14 aryl, —C 3 -C 8 cycloalkyl, —C 6 -C 14 aryl, heteroaryl or heterocyclyl;
R 1 and R 2 are independently selected from hydrogen and lower alkyl;
p is independently an integer from 1 to 3;
wherein each of the above alkyl, cycloalkyl, aryl, heterocyclyl and heteroaryl are unsubstituted or substituted with one or more of the same or different groups selected from halogen, hydroxy, carbonyl, carboxy, ester, ether, acyl, acyloxy, cyano, amino, amide, imino, alkylthio, thioester, sulfonyl, nitro, —C 1 -C 6 alkyl, halo—C 1 -C 6 alkyl, halo—C 1 -C 6 alkoxy, —C 1 -C 6 alkoxy, —C 3 -C 8 cycloalkyl, —(CR 1 R 2 ) p —C 6 -C 10 aryl, —C 6 -C 10 aryl, —NHCOMe, —S(O) 2 Me, aryloxy, heterocyclyl and heteroaryl group; or
a stereoisomer, tautomer, N-oxide or a pharmaceutically acceptable salt thereof.
12. The compound according to claim 1 , selected from:
N-methyl-N′-((6-(pyridin-3-yl)imidazo[1,2-a]pyridin-3-yl)methylene)benzenesulfonohydrazide;
N,3-dimethyl-N′-((6-pyridin-3-yl)imidazo[1,2-a]pyridine-3-yl)methylene) benzenesulfonohydrazide;
N,4-dimethyl-N′-((6-(pyridine-3-yl)imidazo[1,2-a]pyridine-3-yl)methylene) benzenesulfonohydrazide;
2-Fluoro-N-methyl-N′-((6-(pyridine-3-yl)imidazo[1,2-a]pyridine-3-yl)methylene) benzenesulfonohydrazide;
3-Fluoro-N-methyl-N′-((6-(pyridine-3-yl)imidazo[1,2-a]pyridine-3-yl) methylene)benzenesulfonohydrazide;
4-Fluoro-N-methyl-N′-((6-(pyridine-3-yl)imidazo[1,2-a]pyridine-3-yl)methylene) benzenesulfonohydrazide;
3-Bromo-N-methyl-N′-((6-(pyridine-3-yl)imidazo[1,2-a]pyridine-3-yl)methylene) benzenesulfonohydrazide;
4-Bromo-N-methyl-N′-((6-(pyridine-3-yl)imidazo[1,2-a]pyridine-3-yl)methylene) benzenesulfonohydrazide;
2-Cyano-N-methyl-N′-((6-(pyridine-3-yl)imidazo[1,2-a]pyridine-3-yl)methylene) benzenesulfonohydrazide;
(E)-3-cyano-N-methyl-N′-((6-(pyridin-3-yl)imidazo[1,2-a]pyridin-3-yl)methylene)benzenesulfonohydrazide;
4-Cyano-N-methyl-N′-((6-(pyridine-3-yl)imidazo[1,2-a]pyridine-3-yl)methylene) benzenesulfonohydrazide;
4-Methoxy-N-methyl-N′-((6-(pyridine-3-yl)imidazo[1,2-a]pyridine-3-yl) methylene)benzenesulfonohydrazide;
2,4-Difluoro-N-methyl-N′-((6-(pyridine-3-yl)imidazo[1,2-a]pyridine-3-yl)methylene) benzenesulfonohydrazide;
2,6-Difluoro-N-methyl-N′-((6-(pyridine-3-yl)imidazo[1,2-a]pyridine-3-yl)methylene) benzenesulfonohydrazide;
3,4-difluoro-N-methyl-N′-((6-(pyridine-3-yl)imidazo[1,2-a]pyridine-3-yl)methylene) benzenesulfonohydrazide;
3,5-Difluoro-N-methyl-N′-((6-(pyridine-3-yl)imidazo[1,2-a]pyridine-3-yl)methylene) benzenesulfonohydrazide;
3-Chloro-2-fluoro-N-methyl-N′-((6-(pyridine-3-yl)imidazo[1,2-a]pyridine-3-yl) methylene)benzenesulfonohydrazide;
3-Chloro-4-fluoro-N-methyl-N′-((6-(pyridine-3-yl)imidazo[1,2-a]pyridine-3-yl) methylene)benzenesulfonohydrazide;
2-Fluoro-N,5-dimethyl-N′-((6-(pyridine-3-yl)imidazo[1,2-a]pyridine-3-yl)methylene) benzenesulfonohydrazide;
3-Fluoro-N,4-dimethyl-N′-((6-(pyridine-3-yl)imidazo[1,2-a]pyridine-3-yl)methylene) benzenesulfonohydrazide;
5-Fluoro-N,2-dimethyl-N′-((6-(pyridine-3-yl)imidazo[1,2-a]pyridine-3-yl)methylene) benzenesulfonohydrazide;
3-(3-((2-(5-fluoro-2-methylphenylsulfonyl)-2-methylhydrazono)methyl)imidazo[1,2-a]pyridin-6-yl)pyridine 1-oxide;
4-Bromo-N,3-dimethyl-N′-((6-(pyridine-3-yl)imidazo[1,2-a]pyridine-3-yl) methylene)benzenesulfonohydrazide;
N-methyl-N′-((6-(pyridine-3-yl)imidazo[1,2-a]pyridine-3-yl)methylene)-3,5-bis (trifluoromethyl)benzenesulfonohydrazide;
3-Cyano-4-fluoro-N-methyl-N′-((6-(pyridine-3-yl)imidazo[1,2-a]pyridine-3-yl) methylene)benzenesulfonohydrazide;
N,2-dimethyl-5nitro-N′-((6-pyridin-3-yl)imidazo[1,2-a]pyridine-3-yl) methylene)benzenesulfonohydrazide;
2-Bromo-4,6-difluoro-N-methyl-N′-((6-(pyridine-3-yl)imidazo[1,2-a]pyridine-3-yl) methylene)benzenesulfonohydrazide;
N,2,4,6-tetramethyl-N′-((6-(pyridine-3-yl)imidazo[1,2-a]pyridine-3-yl)methylene) benzenesulfonohydrazide;
N-methyl-1-phenyl-N′-((6-pyridin-3-yl)imidazo[1,2-a]pyridine-3-yl)methylene) benzenesulfonohydrazide;
N-methyl-N′-((6-(pyridine-3-yl)imidazo[1,2-a]pyridine-3-yl)methylene)thiophene-2-sulfonohydrazide;
N-methyl-N′-((6-(pyridine-3-yl)imidazo[1,2-a]pyridine-3-yl)methylene) quinoline-8-sulfonohydrazide;
N-methyl-N′-((6-(pyridine-3-yl)imidazo[1,2-a]pyridine-3-yl)methylene) cyclohexanesulfonohydrazide;
3-Fluoro-N,4-dimethyl-N′-((6-(pyridine-3-yl)imidazo[1,2-a]pyridine-3-yl)methylene) benzenesulfonohydrazide;
3-Cyano-4-fluoro-N-methyl-N′-((6-(pyridine-3-yl)imidazo[1,2-a]pyridine-3-yl) methylene)benzenesulfonohydrazide;
(E)-2,3,4-Trifluoro-N-methyl-N′-((6-(pyridin-3-yl)imidazo[1,2-a]pyridin-3-yl) methylene)benzenesulfonohydrazide;
(E)-4-bromo-2,5-difluoro-N-methyl-N′-((6-(pyridin-3-yl)imidazo[1,2-a]pyridin-3-yl) methylene)benzenesulfonohydrazide;
(E)-2-bromo-4-fluoro-N-methyl-N′-((6-(pyridin-3-yl)imidazo[1,2-a]pyridin-3-yl) methylene)benzenesulfonohydrazide;
(E)-N-methyl-N′-((6-(pyridin-3-yl)imidazo[1,2-a]pyridin-3-yl)methylene)-3-(trifluoromethyl) benzenesulfonohydrazide;
(E)-4-bromo-2,6-dichloro-N-methyl-N′-((6-(pyridin-3-yl)imidazo[1,2-a]pyridin-3-yl) methylene)benzenesulfonohydrazide;
(E)-3-chloro-N-methyl-N′-((6-(pyridin-3-yl)imidazo[1,2-a]pyridin-3-yl) methylene)benzenesulfonohydrazide;
(E)-2-chloro-N-methyl-N′-((6-(pyridin-3yl)imidazo[1,2-a]pyridin-3-yl)methylene)-4-(trifluoromethyl)benzenesulfonohydrazide;
(E)-2-chloro-4-fluoro-N-methyl-N′((6-(pyridin-3-yl)imidazo[1,2-a]pyridin-3-yl) methylene)benzenesulfonoydrazide;
(E)-N,1,2-trimethyl-N′-((6-(pyridin-3-yl)imidazo[1,2-a]pyridin-3-yl)methylene)-1H-imidazole-4-sulfonohydrazide;
(E)-4-chloro-N,2,5-trimethyl-N′((6-(pyridin-3-yl)imidazo [1,2-a]pyridin-3-yl)methylene) benzenesulfonohydrazide;
(E)-2,5-difluoro-N-methyl-N′-((6-(pyridin-3-yl)imidazo[1,2-a]pyridin-3-yl)methylene) benzenesulfonohydrazide;
(E)-5-fluoro-2-methoxy-N-methyl-N′((6-(pyridin-3-yl)imidazo[1,2-a]pyridin-3-yl) methylene)benzenesulfonohydrazide;
(E)-4-Iodo-N-methyl-N′-((6-(pyridin-3-yl)imidazo[1,2-a]pyridin-3-yl) methylene)benzenesulfonohydrazide;
(E)-2′-Fluoro-N-methyl-N′-((6-(pyridin-3-yl)imidazo[1,2-a]pyridin-3-yl)methylene)-5′-(trifluoromethyl)biphenyl-4-sulfonohydrazide;
4-Methyl-3-(1-methyl-2-((6-(pyridin-3-yl)imidazo[1,2-a]pyridin-3-yl)methylene) hydrazinylsulfonyl)benzoic acid;
4-Methoxy-3-(1-methyl-2-((6-(pyridin-3-yl)imidazo[1,2-a]pyridin-3-yl) methylene)hydrazinylsulfonyl)benzamide;
(E)-N,2,5-trimethyl-N′((6-(pyridin-3-yl)imidazo[1,2-a]pyridin-3-yl)methylene) benzenesulfonohydrazide;
(E)-2,5-dibromo-N-methyl-N′-((6-(pyridin-3-yl)imidazo[1,2-a]pyridin-3-yl)methylene) benzenesulfonohydrazide;
(E)-2,5-dimethoxy-N-methyl-N′((6-(pyridin-3-yl)imidazo[1,2-a]pyridin-3-yl)methylene) benzenesulfonohydrazide;
(E)-N,2-dimethyl-N′-((6-(pyridin-3-yl)imidazo[1,2-a]pyridin-3-yl)methylene) benzenesulfonohydrazide;
(E)-N-methyl-N′-((6-(pyridin-3-yl)imidazo[1,2-a]pyridin-3-yl)methylene)-2-(trifluoromethoxy )benzenesulfonohydrazide;
(E)-5-chloro-2-methoxy-N-methyl-N-′-((6-(pyridin-3-yl)imidazo[1,2-a]pyridin-3-yl) methylene)benzenesulfonohydrazide;
(E)-4-bromo-N-methyl-N′-((6-(pyridin-3-yl)imidazo[1,2-a]pyridin-3-yl)methylene)-2-(trifluoromethoxy)benzenesulfonohydrazide;
(E)-2-bromo-N-methyl-N′-((6-(pyridin-3-yl)imidazo[1,2-a]pyridin-3-yl)methylene)-5-(trifluoromethyl)benzenesulfonohydrazide;
(E)-N-methyl-2-nitro-N′-((6-(pyridin-3-yl)imidazo[1,2-a]pyridin-3-yl) methylene)benzenesulfonohydrazide;
(E)-N-methyl-2-(methylsulfonyl)-N′-((6-(pyridin-3-yl)imidazo[1,2-a]pyridin-3-yl) methylene)benzenesulfonohydrazide
(E)-N-methyl-2-phenoxy-N′-((6-(pyridin-3-yl)imidazo[1,2-a]pyridin-3-yl) methylene)benzenesulfonohydrazide;
(E)-N-methyl-N′-((6-(pyridin-3-yl)imidazo[1,2-a]pyridin-3-yl)methylene) hexane-1-sulfonohydrazide;
(E)-N-methyl-2-morpholino-N′-((6-(pyridin-3-yl)imidazo[1,2-a]pyridin-3-yl)methylene)-5-(trifluoromethyl)benzenesulfonohydrazide;
(E)-N,2-dimethyl-5-(methylsulfonyl)-N′-((6-(pyridin-3-yl)imidazo[1,2-a]pyridin-3-yl) methylene)benzenesulfonohydrazide;
(E)-2-bromo-N-methyl-N′-((6-(pyridin-3-yl)imidazo[1,2-a]pyridin-3-yl)methylene) benzenesulfonohydrazide;
(E)-2-chloro-N-methyl-N′-((6-(pyridin-3-yl)imidazo[1,2-a]pyridin-3-yl)methylene)-5-(trifluoromethyl)benzenesulfonohydrazide;
(E)-N-methyl-6-morpholino-N′-((6-(pyridin-3-yl)imidazo[1,2-a]pyridin-3-yl)methylene) pyridine-3-sulfonohydrazide
(E)-Methyl1-methyl-5-(1-methyl-2-((6-(pyridin-3-yl)imidazo[1,2-a]pyridin-3-yl) methylene)hydrazinylsulfonyl)-1H-pyrrole-2-carboxylate;
(E)-N,4-dimethyl-N′-((6-(pyridin-3-yl)imidazo[1,2-a]pyridin-3-yl)methylene)-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazine-7-sulfonohydrazide;
(E)-N-methyl-N′-((6-(pyridin-3-yl)imidazo[1,2-a]pyridin-3-yl)methylene)pyridine-3-sulfonohydrazide;
(E)-N-methyl-4-phenoxy-N′-((6-(pyridin-3-yl)imidazo[1,2-a]pyridin-3-yl)methylene) benzenesulfonohydrazide;
(E)-Methyl3-(1-methyl-2-((6-(pyridin-3-yl)imidazo[1,2-a]pyridin-3-yl)methylene) hydrazinylsulfonyl)thiophene-2-carboxylate;
(E)-N-methyl-N′-((6-(pyridin-3-yl)imidazo[1,2-a]pyridin-3-yl)methylene)biphenyl-4-sulfonohydrazide;
(E)-Methyl5-(1-methyl-2-((6-(pyridin-3-yl)imidazo[1,2-a]pyridin-3-yl)methylene)hydrazinylsulfonyl) furan-2-carboxylate;
(E)-4-chloro-N-methyl-3-nitro-N′-((6-(pyridin-3-yl)imidazo[1,2-a]pyridin-3-yl)methylene) benzenesulfonohydrazide;
(E)-5-bromo-2-methoxy-N-methyl-N′-((6-(pyridin-3-yl)imidazo[1,2-a]pyridin-3-yl) methylene)benzenesulfonohydrazide;
(E)-3-chloro-N,2-dimethyl-N′-((6-(pyridin-3-yl)imidazo[1,2-a]pyridin-3-yl)methylene) benzenesulfonohydrazide;
(E)-5-chloro-2-fluoro-N-methyl-N′-((6-(pyridin-3-yl)imidazo[1,2-a]pyridin-3-yl) methylene)benzenesulfonohydrazide;
(E)-4-Fluoro-N,2-dimethyl-N′-((6-(pyridin-3-yl)imidazo[1,2-a]pyridin-3-yl)methylene) benzenesulfonohydrazide;
(E)-2-methoxy-N,6-dimethyl-N′-((6-(pyridin-3-yl)imidazo[1,2-a]pyridin-3-yl) methylene)benzenesulfonohydrazide;
(E)-4-Bromo-2-chloro-N-methyl-N′-((6-(pyridin-3-yl)imidazo[1,2-a]pyridin-3-yl) methylene)benzenesulfonohydrazide;
(E)-2-chloro-N-methyl-N′-((6-(pyridin-3-yl)imidazo[1,2-a]pyridin-3-yl)methylene) benzenesulfonohydrazide;
(E)-N-(4-(1-methyl-2-((6-(pyridin-3-yl)imidazo[1,2-a]pyridin-3-yl)methylene) hydrazinylsulfonyl)phenyl)acetamide;
N′-((6-(6-fluoropyridine-3-yl)imidazo[1,2-a]pyridine-3-yl)methylene)-n,2-dimethyl-5-nitrobenzenesulfonohydrazide;
(E)-N-ethyl-2-methyl-5-nitro-N′-((6-(pyridin-3-yl)imidazo[1,2-a]pyridin-3-yl) methylene)benzenesulfonohydrazide;
N,2-dimethyl-5-nitro-N′-((6-(pyridine-4-yl)imidazo[1,2-a]pyridine-3-yl)methylene) benzenesulfonohydrazide;
5-Fluoro-N,2-dimethyl-N′-((6-(pyridine-4-yl)imidazo[1,2-a]pyridine-3-yl)methylene) benzenesulfonohydrazide;
(E)-5-Fluoro-N′-((6-(2-fluoropyridin-3-yl)imidazo[1,2-a]pyridin-3-yl)methylene)-N,2-dimethylbenzenesulfonohydrazide;
(E)-5-Fluoro-N′-((6-(2-fluoropyridin-3-yl)imidazo[1,2-a]pyridin-3-yl)methylene)-2-methoxy-N-methylbenzenesulfonohydrazide;
(E)-3-fluoro-N′-((6-(2-fluoropyridin-3-yl)imidazo[1,2-a]pyridin-3-yl)methylene)-N-methylbenzenesulfonohydrazide;
(E)-5-chloro-2-fluoro-N′46-(2-fluoropyridin-3-yl)imidazo[1,2-a]pyridin-3-yl)methylene)-N-methylbenzenesulfonohydrazide;
(E)-5-bromo-N′-((6-(2-fluoropyridin-3-yl)imidazo[1,2-a]pyridin-3-yl)methylene)-2-methoxy-N-methylbenzenesulfonohydrazide
(E)-N′-((6-(2-fluoropyridin-3-yl)imidazo[1,2-a]pyridin-3-yl)methylene)-2,5-dimethoxy-N-methylbenzenesulfonohydrazide;
(E)-N′-((6-(2-fluoropyridin-3-yl)imidazo[1,2-a]pyridin-3-yl)methylene)-N,2-dimethyl-5-(methylsulfonyl)benzenesulfonohydrazide;
(E)-N′-((6-(2-fluoropyridin-3-yl)imidazo[1,2-a]pyridin-3-yl)methylene)-N-methylhexane-1-sulfonohydrazide;
(E)-N′-((6-(2-fluoropyridin-3-yl)imidazo[1,2-a]pyridin-3-yl)methylene)-2-methoxy-N,4-dimethylbenzenesulfonohydrazide;
(E)-2-bromo-N′-((6-(2-fluoropyridin-3-yl)imidazo[1,2-a]pyridin-3-yl)methylene)-N-methylbenzenesulfonohydrazide;
(E)-2-cyano-N′-((6-(2-fluoropyridin-3-yl)imidazo[1,2-a]pyridin-3-yl)methylene)-N-methylbenzenesulfonohydrazide;
(E)-N′-((6-(2-fluoropyridin-3-yl)imidazo[1,2-a]pyridin-3-yl)methylene)-2-methoxy-N,5-dimethylbenzenesulfonohydrazide;
N,2-Dimethyl-5-nitro-N′-((6-(quinolin-3-yl)imidazo[1,2-a]pyridine-3-yl)methylene) benzenesulfonohydrazide;
(E)-5-Fluoro-N,2-dimethyl-N′-((8-methyl-6-(pyridin-3-yl)imidazo[1,2-a]pyridin-3-yl)methylene)benzenesulfonohydrazide;
(E)-3,5-Difluoro-N-methyl-N′-((8-methyl-6-(pyridin-3-ypimidazo[1,2-a]pyridin-3-yl)methylene)benzenesulfonohydrazide;
(E)-4-Bromo-2,6-difluoro-N-methyl-N′-((8-methyl-6-(pyridin-3-yl)imidazo[1,2-a]pyridin-3-yl)methylene)benzenesulfonohydrazide;
(E)-N,3-dimethyl-N′-((8-methyl-6-(pyridin-3-yl)imidazo[1,2-a]pyridin-3-yl)methylene)benzenesulfonohydrazide;
(E)-2-cyano-N-methyl-N′-((8-methyl-6-(pyridin-3-yl)imidazo[1,2-a]pyridin-3-yl)methylene)benzenesulfonohydrazide;
(E)-3-cyano-4-fluoro-N-methyl-N′-((8-methyl-6-(pyridin-3-yl)imidazo[1,2-a]pyridin-3-yl)methylene)benzenesulfonohydrazide;
(E)-3-cyano-N-methyl-N′-((8-methyl-6-(pyridin-3-yl)imidazo[1,2-a]pyridin-3-yl)methylene)benzenesulfonohydrazide;
(E)-4-Bromo-N,3-dimethyl-N′-((8-methyl-6-(pyridin-3-yl)imidazo[1,2-a]pyridin-3-yl)methylene)benzenesulfonohydrazide;
(E)-3-Methoxy-N-methyl-N′-((8-methyl-6-(pyridin-3-yl)imidazo[1,2-a]pyridin-3-yl)methylene)benzenesulfonohydrazide;
(E)-N-methyl-N′-((8-methyl-6-(pyridin-3-yl)imidazo[1,2-a]pyridin-3-yl)methylene)-3-nitrobenzenesulfonohydrazide;
(E)-3-Chloro-N-methyl-N′-((8-methyl-6-(pyridin-3-yl)imidazo[1,2-a]pyridin-3-yl)methylene)benzenesulfonohydrazide;
(E)-N-methyl-N′-((8-methyl-6-(pyridin-3-yl)imidazo[1,2-a]pyridin-3-yl)methylene)-3-(trifluoromethyl)benzenesulfonohydrazide;
(E)-2-Bromo-4,6-difluoro-N-methyl-N′-((8-methyl-6-(pyridin-3-yl)imidazo[1,2-a]pyridin-3-yl)methylene)benzenesulfonohydrazide;
(E)-4-Chloro-N-methyl-N′-((8-methyl-6-(pyridin-3-yl)imidazo[1,2-a]pyridin-3-yl)methylene)-3-nitrobenzenesulfonohydrazide;
(E)-2-Bromo-4-fluoro-N-methyl-N′((8-methyl-6-(pyridin-3-yl)imidazo[1,2-a]pyridin-3-yl)methylene)benzenesulfonohydrazide;
(E)-N′-((6-(1H-indol-2-yl)imidazo[1,2-a]pyridin-3-yl)methylene)-5-fluoro-N,2-dimethylbenzenesulfonohydrazide;
(E)-5-fluoro-N,2-dimethyl-N′-((6-(1-methyl-1H-indol-3-yl)imidazo[1,2-a]pyridin-3-yl)methylene benzenesulfonohydrazide;
2-Cyano-N-methyl-N′((7-methyl-6-(pyridin-3-yl)imidazo [1,2-a]pyridin-3-yl)methylene) benzenesulfonohydrazide;
5-Fluoro-N,2-dimethyl-N′-((7-methyl-6-(pyridin-3-yl)imidazo [1,2-a]pyridin-3-yl) methylene)benzenesulfonohydrazide;
N,3-dimethyl-N′-((7-methyl-6-(pyridin-3-yl)imidazo [1,2-a]pyridin-3-yl) methylene)benzenesulfonohydrazide;
3-Fluoro-N-methyl-N′((7-methyl-6-(pyridin-3-yl)imidazo[1,2-a]pyridin-3-yl)methylene) benzenesulfonohydrazide;
3-Chloro-N-methyl-N′-((7-methyl-6-(pyridin-3-yl)imidazo[1,2-a]pyridin-3-yl)methylene )benzenesulfonohydrazide;
N-methyl-N′-((7-methyl-6-(pyridin-3-yl)imidazo[1,2-a]pyridin-3-yl)methylene)-3-(trifluoromethyl)benzenesulfonohydrazide;
3-Bromo-N-methyl-N′((7-methyl-6-(pyridin-3-yl)imidazo[1,2-a]pyridin-3-yl) methylene)benzenesulfonohydrazide;
5-Fluoro-N,2-dimethyl-N′-((7-methyl-6-(pyridin-3-yl)imidazo [1,2-a]pyridin-3-yl) methylene)benzenesulfonohydrazide;
N′-((6-(2,4-dimethoxypyrimidin-5-yl)imidazo[1,2-a]pyridin-3-yl)methylene)-5-fluoro-N,2-dimethylbenzenesulfonohydrazide;
(E)-5-Fluoro-N,2-dimethyl-N′-((5-methyl-6-(pyridin-3-yl)imidazo[1,2-a]pyridin-3-yl)methylene)benzenesulfonohydrazide;
(E)-N,3-dimethyl-N′-((5-methyl-6-(pyridin-3-yl)imidazo[1,2-a]pyridin-3-yl)methylene)benzenesulfonohydrazide;
(E)-5-fluoro-N,2-dimethyl-N′-((6-(6-methylpyridin-3-yl)imidazo[1,2-a]pyridin-3-yl)methylene)benzenesulfonohydrazide;
(E)-N-methyl-N′-((6-(6-methylpyridin-3-yl)imidazo[1,2-a]pyridin-3-yl)methylene)-2-(trifluoromethoxy)benzenesulfonohydrazide;
(E)-5-Fluoro-2-methoxy-N-methyl-N′-((6-(6-methylpyridin-3-yl)imidazo [1,2-a]pyridin-3-yl)methylene)benzenesulfonohydrazide;
(E)-N,2-dimethyl-N′((6-(6-methylpyridin-3-yl)imidazo[1,2-a]pyridin-3-yl)methylene)benzenesulfonohydrazide;
(E)-5-fluoro-N′-((6-(5-fluoropyridin-3-yl)imidazo[1,2-a]pyridin-3-yl)methylene)-N,2-dimethyl benzenesulfonohydrazide;
(E)-5-Fluoro-N′((6-(5-fluoropyridin-3-yl)imidazo[1,2-a]pyridin-3-yl)methylene)-2-methoxy-N-methyl benzenesulfonohydrazide;
(E)-5-Fluoro-N′-((6-(6-fluoro-5-methylpyridin-3-yl)imidazo[1,2-a]pyridin-3-yl)methylene)-N,2-dimethyl benzenesulfonohydrazide;
(E)-N′-((6-(6-Chloropyridins-3-yl)imidazo[1,2-a]pyridin-3-yl)methylene)-5-fluoro-N,2-dimethylbenzenesulfonohydrazide;
(E)-N′-((6-(1H-Pyrrol-2-yl)imidazo[1,2-a]pyridin-3-yl)methylene)-5-fluoro-N,2-dimethyl benzenesulfonohydrazide;
(E)-5-fluoro-N′-((6-(6-methoxypyridin-3-yl)imidazo[1,2-a]pyridin-3-yl)methylene)-N,2-dimethyl benzenesulfonohydrazide;
(E)-5-Fluoro-N-((6-(2-methoxypyrimidin-5-yl)imidazo[1,2-a]pyridine-3-yl)methylene)-N,2-dimethylbenzenesulfonohydrazide;
(E)-5-fluoro-N,2-dimethyl-N′-((6-(5-(trifluoromethyl)pyridin-3-yl)imidazo [1,2-a]pyridin-3-yl)methylene)benzenesulfonohydrazide;
(E)-5-Fluoro-N,2-dimethyl-N-((6-(pyrimidin-5-ypimidazo[1,2-a]pyridin-3-yl)methylene)benzenesulfonohydrazide;
(E)-N-benzyl-1-methyl-2-((6-(pyridin-3-yl)imidazo[1,2-a]pyridin-3-yl)methylene)hydrazinecarboxamide;
(E)-1-methyl-2-((6-(pyridin-3-yl)imidazo[1,2-a]pyridin-3-yl)methylene)-N-p-tolylhydrazinecarboxamide;
(E)-N-(2-fluoro-5-methylphenyl)-1-methyl-2-((6-(pyridin-3-yl)imidazo[1,2-a]pyridin-3-yl)methylene)hydrazinecarboxamide;
(E)-N-(5-fluoro-2-methylphenyl)-1-methyl-2-((6-(pyridin-3-yl)imidazo[1,2-a]pyridin-3-yl)methylene)hydrazinecarboxamide;
N-benzyl-2-((6-bromoimidazo[1,2-a]pyridin-3-yl)methylene)-1-methyl hydrazinecarboxamide;
(6-bromoimidazo[1,2-a]pyridin-3-yl)methylene)-N-(2-fluoro-5-methylphenyl)-1-methylhydrazinecarboxamide;
(6-bromoimidazo[1,2-a]pyridin-3-yl)methylene)-N-(5-fluoro-2-methlphenyl)-1-methylhydrazinecarboxamide;
(E)-1-methyl-N-(2-morpholinoethyl)-2-((6-(pyridin-3-yl)imidazo[1,2-a]pyridin-3-yl)methylene)hydrazinecarbothioamide;
(E)-N-(4-cyanophenyl)-1-methyl-2-((6-(pyridin-3-yl)imidazo[1,2-a]pyridin-3-yl)methylene)hydrazinecarbothioamide;
(E)-N-(4-methoxyphenyl)-1-methyl-2-((6-(pyridin-3-yl)imidazo[1,2-a]pyridin-3-yl)methylene)hydrazinecarbothioamide;
2-((6-bromoimidazo[1,2-a]pyridin-3-yl)methylene)-1-methyl-N-(2-morpholinoethyl)hydrazinecarbothioamide;
2-((6-bromoimidazo[1,2-a]pyridin-3-yl)methylene)-1-methyl-N-(4-(trifluoromethyl)phenyl)hydrazinecarbothioamide; or
a stereoisomer, tautomer, N-oxide or a pharmaceuticallyacceptable salt thereof.
13. A pharmaceutical composition, comprising a therapeutically effective amount of a compound of formula (I) according claim 1 or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable excipient or carrier.
14. A method for the treatment of a disease mediated by PI3K (phosphatidylinositol-3-kinase) or mTOR (mammalian target of rapamycin) or STAT3(Signal transducer and activator of transcription 3) or a combination thereof, comprising, administering to a mammal in need thereof a therapeutically effective amount of a compound of formula (I) according to claim 1 or a pharmaceutically acceptable salt thereof, wherein the disease is cancer is selected from the group consisting of small-cell-lung cancer, non-small-cell lung cancer, prostate cancer, ovarian cancer, colorectal cancer, pancreatic cancer, breast cancer and glioblastoma.
15. A method for the treatment of a disease mediated by TNF-αor IL-6 , comprising administering to a mammal in need thereof a therapeutically effective amount of a compound of formula (I) according to claim 1 or a pharmaceutically acceptable salt thereof, wherein the disease mediated by TNF-αor IL-6 is selected from the group consisting of psoriasis, inflammatory bowel disease, inflammation, rheumatoid arthritis, juvenile rheumatoid arthritis, psoriatic arthritis, osteoarthritis, refractory rheumatoid arthritis, chronic non-rheumatoid arthritis, osteoporosis/bone resorption, Crohn's disease, atherosclerosis, ulcerative colitis, and ankylosing spondylitis.
16. The method according to claim 15 , wherein the disease mediated by TNF-α or IL-6is selected from the group consisting of rheumatoid arthritis, Crohn's disease, ulcerative colitis, psoriasis and atherosclerosis.
17. A process for the preparation of a compound of formula (I)
wherein, Q is SO 2 ; R a , R b and R d are hydrogen or methyl; R c , R e and R f are as defined for formula (I) in claim 1 , comprising
refluxing a compound of formula (3)
with a compound of formula H 2 N—NH—R e in presence of an alcoholic solvent followed by reacting with a compound of formula R f SO 2 X, wherein Q is SO 2 ; X is halogen, R a , R b and R d are independently hydrogen or methyl, R c , R e and R f are as defined above for formula (I) in presence of pyridine as a base;
optionally converting the resulting compound into a pharmaceutically acceptable salt.
18. A process for the preparation of a compound of formula (I)
wherein, Q is —C(O)NH or —C(S)NH; R a , R b and R d are independently hydrogen or methyl, R c , R e and R f are as defined for formula (I) in claim 1 , which comprises, refluxing a compound of formula (3)
with a compound of formula H 2 N—NH—R e in presence of an alcoholic solvent followed by reacting with a compound of formula O═C═N═R f or S═C═N═R f , wherein R a , R b and R d are hydrogen or methyl, R c , R e and R f are as defined above for formula (I);
optionally converting the resulting compound into a pharmaceutically acceptable salt.