Preparation method of dihydroindene amide compounds, their pharmaceutical compositions containing compounds thereof and use as protein kinases inhibitor
The invention provides a new kind of dihydroindene amide compounds of general formula I or their pharmaceutically acceptable salts or prodrug thereof which can be used as protein kinase inhibitor. The invention provides a preparation method of the kind of compounds, the pharmaceutical compositions containing the compounds, the method for preventing or curing the diseases related to the abnormity of activities of protein kinases, especially Abl, Bcr-Abl, c-Kit and PDGFR, using them as protein kinase inhibitor, and their preparation use of drug used for preventing or curing the diseases related to the abnormity of activities of protein kinases, especially Abl, Bcr-Abl, c-Kit and PDGFR.
1. A compound of Formula I:
or its pharmaceutically acceptable salt or prodrug thereof, wherein:
R 1 is a piperazinyl, which can be optionally substituted by 1, 2, 3 or 4 R 1a ;
R 1a is H, halogen, cyano-group, C 1-6 alkyl, C 1-6 hydroxyalkyl, C 1-6 haloalkyl, C 1-6 cyanoalkyl, OR a , SR a , NR b R c , NR b C(O)R d , NR b S(O) 2 R d , C(O)NR b R c , C(O)R d , C(O)OR a , S(O) 2 R d , C 2-6 alkenyl, C 2-6 alkynyl, aryl, heteroaryl, cycloalkyl or heterocycloalkyl, wherein the said C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, aryl, heteroaryl, cycloalkyl or heterocycloalkyl can be optionally substituted with 1, 2 or 3 groups independently selected from cyano-group, halogen, OR a , SR a , NR b R c , NR b (CO)R d , NR b S(O) 2 R d , C(O)NR b R c , S(O) 2 NR b R c , C(O)R d , C(O)OR a , S(O) 2 R d , C 1-6 haloalkyl, C 1-6 hydroxyalkyl, C 1-6 cyanoalkyl, aryl, heteroaryl, cycloalkyl, and heterocycloalkyl;
Alternatively, two R 1a groups taken together with the atoms attached to them can form a cycloalkyl and heterocycloalkyl of 3, 4, 5, 6 or 7-membered ring, and can be optionally substituted by 1, 2 or 3 groups independently selected from cyano-group, halogen, OR a , SR a , NR b R c , NR b (CO)R d , NR b S(O) 2 R d , C(O)NR b R c , S(O) 2 NR b R c , C(O)R d , C(O)OR a , S(O) 2 R d , C 1-6 haloalkyl, C 1-6 hydroxyalkyl, C 1-6 cyanoalkyl, C 2-6 alkenyl, C 2-6 alkynyl, aryl, heteroaryl, cycloalkyl, and heterocycloalkyl;
R 2 is H, halogen, cyano-group, OR a , SR a , NR b R c , C 1-6 alkyl, C 1-6 hydroxyalkyl, C 1-6 haloalkyl, C 1-6 cyanoalkyl, C 2-6 alkenyl or C 2-6 alkynyl;
Alternatively, two R 2 groups taken together with the atoms attached to them can form a cycloalkyl and heterocycloalkyl of 3, 4, 5, 6 or 7-membered ring, and can be optionally substituted by 1, 2 or 3 groups independently selected from cyano-group, halogen, OR a , SR a , NR b R c , NR b (CO)R d , NR b S(O) 2 R d , C(O)NR b R c , S(O) 2 NR b R c , C(O)R d , C(O)OR a , S(O) 2 R d , C 1-6 haloalkyl, C 1-6 hydroxyalkyl, C 1-6 cyanoalkyl, C 2-6 alkenyl, and C 2-6 alkynyl;
R 3 is H, halogen, cyano-group, OR a , SR a , NR b R c , C 1-6 alkyl, C 1-6 hydroxyalkyl, C 1-6 haloalkyl, C 1-6 cyanoalkyl, C 2-6 alkenyl, C 2-6 alkynyl, cycloalkyl, or heterocycloalkyl;
Alternatively, two R 3 groups taken together with the atoms attached to them can form a cycloalkyl and heterocycloalkyl of 5, 6 or 7-membered ring, and can be optionally substituted by 1, 2 or 3 groups independently selected from halogen, cyano-group, OR a , SR a , NR b R c , C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 hydroxyalkyl, C 1-6 cyanoalkyl, C 2-6 alkenyl, and C 2-6 alkynyl;
W—X is amide bond;
Y is heteroaryl, which can be optionally substituted by 1, 2 or 3 R 4 ;
Z is heteroaryl, which can be optionally substituted by 1, 2 or 3 R 5 ;
R 4 and R 5 are independently selected from halogen, cyano-group, OR a , SR a , NR b R c , C 1-6 alkyl, C 1-6 hydroxyalkyl, C 1-6 haloalkyl, C 1-6 cyanoalkyl, C 2-6 alkenyl, C 2-6 alkynyl, NR b (CO)R d , C(O)NR b R c , NR b S(O) 2 R d , S(O) 2 NR b R c , C(O)R d , C(O)OR a , S(O) 2 R d , cycloalkyl, heterocycloalkyl, aryl, and heteroaryl;
Alternatively, two R 4 or two R 4 groups taken together with the atoms attached to them respectively, can form a cycloalkyl and heterocycloalkyl of 5, 6 or 7-membered ring, and can be optionally substituted by 1, 2 or 3 groups independently selected from halogen, cyano-group, OR a , SR a , NR b R c , C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 hydroxyalkyl, C 1-6 cyanoalkyl, C 2-6 alkenyl, and C 2-6 alkynyl;
R a , R b , R c and R d are independently selected from H, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 hydroxyalkyl, C 1-6 cyanoalkyl, C 2-6 alkenyl, C 2-6 alkynyl, aryl, heteroaryl, cycloalkyl, and heterocycloalkyl;
Alternatively, the R b and R c groups taken together with the nitrogen atom attached to them can form a heterocycloalkyl of 4, 5, 6 or 7-membered ring, and can be optionally substituted by 1, 2 or 3 groups independently selected from halogen, cyano-group, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 hydroxyalkyl, C 1-6 cyanoalkyl, C 2-6 alkenyl, C 2-6 alkynyl, aryl, heteroaryl, cycloalkyl, and heterocycloalkyl;
n is an integer from zero to four; and
m is an integer from zero to two.
2. A compound of Formula II:
or its pharmaceutically acceptable salt or prodrug,
wherein:
R 1 is a piperazinyl, which can be optionally substituted by 1, 2, 3 or 4 R 1a ;
R 1a is H, halogen, cyano-group, C 1-6 alkyl, C 1-6 hydroxyalkyl, C 1-6 haloalkyl, C 1-6 cyanoalkyl, OR a , SR a , NR b R c , NR b C(O)R d , NR b S(O) 2 R d , C(O)NR b R c , C(O)R d , C(O)OR a , S(O) 2 R d , C 2-6 alkenyl, C 2-6 alkynyl, aryl, heteroaryl, cycloalkyl or heterocycloalkyl, wherein the said C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, aryl, heteroaryl, cycloalkyl or heterocycloalkyl can be optionally substituted with 1, 2 or 3 groups independently selected from cyano-group, halogen, OR a , SR a , NR b R c , NR b (CO)R d , NR b S(O) 2 R d , C(O)NR b R c , S(O) 2 NR b R c , C(O)R d , C(O)OR a , S(O) 2 R d , C 1-6 haloalkyl, C 1-6 hydroxyalkyl, C 1-6 cyanoalkyl, aryl, heteroaryl, cycloalkyl, and heterocycloalkyl;
Alternatively, two R 1a groups taken together with the atoms attached to them can form a cycloalkyl and heterocycloalkyl of 3, 4, 5, 6 or 7-membered ring, and can be optionally substituted by 1, 2 or 3 groups independently selected from cyano-group, halogen, OR a , SR a , NR b R c , NR b (CO)R d , NR b S(O) 2 R d , C(O)NR b R c , S(O) 2 NR b R c , C(O)R d , C(O)OR a , S(O) 2 R d , C 1-6 haloalkyl, C 1-6 hydroxyalkyl, C 1-6 cyanoalkyl, C 2-6 alkenyl, C 2-6 alkynyl, aryl, heteroaryl, cycloalkyl, and heterocycloalkyl;
Y is heteroaryl, which can be optionally substituted by 1, 2 or 3 R 4 ;
Z is heteroaryl, which can be optionally substituted by 1, 2 or 3 R 5 ;
R 4 and R 5 are independently selected from halogen, cyano-group, OR a , SR a , NR b R c , C 1-6 alkyl, C 1-6 hydroxyalkyl, C 1-6 haloalkyl, C 1-6 cyanoalkyl, C 2-6 alkenyl, C 2-6 alkynyl, NR b (CO)R d , C(O)NR b R c , NR b S(O) 2 R d , S(O) 2 NR b R c , C(O)R d , C(O)OR a , S(O) 2 R d , cycloalkyl, heterocycloalkyl, aryl, and heteroaryl;
Alternatively, two R 4 or two R 4 groups taken together with the atoms attached to them respectively, can form a cycloalkyl and heterocycloalkyl of 5, 6 or 7-membered ring, and can be optionally substituted by 1, 2 or 3 groups independently selected from halogen, cyano-group, OR a , SR a , NR b R c , C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 hydroxyalkyl, C 1-6 cyanoalkyl, C 2-6 alkenyl, and C 2-6 alkynyl;
R a , R b , R c and R d are independently selected from H, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 hydroxyalkyl, C 1-6 cyanoalkyl, C 2-6 alkenyl, C 2-6 alkynyl, aryl, heteroaryl, cycloalkyl, and heterocycloalkyl;
Alternatively, the R b and R c groups taken together with the nitrogen atom attached to them can form a heterocycloalkyl of 4, 5, 6 or 7-membered ring, and can be optionally substituted by 1, 2 or 3 groups independently selected from halogen, cyano-group, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 hydroxyalkyl, C 1-6 cyanoalkyl, C 2-6 alkenyl, C 2-6 alkynyl, aryl, heteroaryl, cycloalkyl, and heterocycloalkyl.
3. The compound or its pharmaceutically acceptable salt or prodrug thereof according to claim 1 , wherein:
R 1 is a piperidinyl, which can be optionally substituted by 1, 2, 3 or 4 R 1a ;
R 1a is H, halogen, cyano-group, C 1-6 alkyl, C 1-6 hydroxyalkyl, C 1-6 haloalkyl, C 1-6 cyanoalkyl, OR a , SR a , NR b R c , NR b C(O)R d , NR b S(O) 2 R d , C(O)NR b R c , C(O)R d , C(O)OR a , S(O) 2 R d , C 2-6 alkenyl, C 2-6 alkynyl, aryl, heteroaryl, cycloalkyl or heterocycloalkyl, wherein the said C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, aryl, heteroaryl, cycloalkyl and heterocycloalkyl can be optionally substituted by 1, 2 or 3 groups independently selected from cyano-group, halogen, OR a , SR a , NR b R c , NR b (CO)R d , NR b S(O) 2 R d , C(O)NR b R c , S(O) 2 NR b C(O)R d , C(O)OR a , S(O) 2 R d , C 1-6 haloalkyl, C 1-6 hydroxyalkyl, C 1-6 cyanoalkyl, aryl, heteroaryl, cycloalkyl, and heterocycloalkyl;
Alternatively, two R 1a groups taken together with the atoms attached to them can form a cycloalkyl and heterocycloalkyl of 3, 4, 5, 6 or 7-membered ring, and can be optionally substituted by 1, 2 or 3 groups independently selected from cyano-group, halogen, OR a , SR a , NR b R c , NR b (CO)R d , NR b S(O) 2 R d , C(O)NR b R c , S(O) 2 NR b R c , C(O)R d , C(O)OR a , S(O) 2 R d , C 1-6 haloalkyl, C 1-6 hydroxyalkyl, C 1-6 cyanoalkyl, C 2-6 alkenyl, C 2-6 alkynyl, aryl, heteroaryl, cycloalkyl, and heterocycloalkyl;
Y is selected from pyridyl, pyrimidyl, pyridazinyl, pyrazinyl, triazinyl, thiazolyl, isothiazolyl, imidazolyl, oxazolyl, isoxazolyl, triazolyl or pyrazolyl, and can be substituted by 1, 2, or 3 R 4 ;
Z is selected from pyridyl, pyrimidyl, pyridazinyl, pyrazinyl, triazinyl, thiazolyl, isothiazolyl, imidazolyl, oxazolyl, isoxazolyl, triazolyl, pyrazolyl, azotic oxazolyl, pyrindol, pyrrolo-pyrimidyl, pyrazolo-pyridyl, pyrazolo-pyrimidyl, quinolyl, isoquinolyl, quinazolyl, piperazinyl or morpholinyl, and can be substituted by 1, 2, or 3 R 5 ;
R 4 and R 5 are independently selected from halogen, cyano-group, OR a , SR a , NR b R c , C 1-6 alkyl, C 1-6 hydroxyalkyl, C 1-6 haloalkyl, C 1-6 cyanoalkyl, C 2-6 alkenyl, C 2-6 alkynyl, NR b (CO)R d , C(O)NR b R c , NR b S(O) 2 R d , S(O) 2 NR b R c , C(O)R d , C(O)OR a , S(O) 2 R d , cycloalkyl, heterocycloalkyl, aryl, and heteroaryl;
Alternatively, two R 4 or two R 5 groups taken together with the atoms attached to them respectively, can form a cycloalkyl and heterocycloalkyl of 5, 6 or 7-membered ring, and can be optionally substituted by 1, 2 or 3 groups independently selected from halogen, cyano-group, OR a , SR a , NR b R c , C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 hydroxyalkyl, C 1-6 cyanoalkyl, C 2-6 alkenyl, and C 2-6 alkynyl;
R a , R b , R c and R d are independently selected from H, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 hydroxyalkyl, C 1-6 cyanoalkyl, C 2-6 alkenyl, C 2-6 alkynyl, aryl, heteroaryl, cycloalkyl, and heterocycloalkyl; and
Alternatively, R b and R c taken together with the nitrogen atom attached to them respectively, can form a heterocycloalkyl of 4, 5, 6 or 7-membered ring, and can be optionally substituted by 1, 2 or 3 groups independently selected from halogen, cyano-group, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 hydroxyalkyl, C 1-6 cyanoalkyl, C 2-6 alkenyl, C 2-6 alkynyl, aryl, heteroaryl, cycloalkyl, and heterocycloalkyl.
4. The compound or its pharmaceutically acceptable salt or prodrug thereof according to claim 1 , having Formula IIa:
wherein:
R 6 and R 7 are independently selected from H, cyano-group, C 1-6 alkyl, C 1-6 hydroxyalkyl, C 1-6 haloalkyl, C 1-6 cyanoalkyl, C 2-6 alkenyl, and C 2-6 alkynyl;
Alternatively, R 6 and R 7 taken together with the atoms attached to them respectively, can form a 5, 6 or 7-membered carbocyclic or heterocyclic ring, and can be optionally substituted by 1, 2 or 3 groups independently selected from halogen, cyano-group, OR a , SR a , NR b R c , C 1-6 alkyl, C 1-6 hydroxyalkyl, C 1-6 haloalkyl, C 1-6 cyanoalkyl, C 2-6 alkenyl and C 2-6 alkynyl;
R 8 is H, C 1-6 alkyl, C 2-6 hydroxyalkyl, C 2-6 haloalkyl, C 1-6 cyanoalkyl, C(O)NR b R c , C(O)R d , C(O)OR a , S(O) 2 R d , C 3-6 alkenyl, C 3-6 alkynyl, aryl, heteroaryl, cycloalkyl or heterocycloalkyl, wherein the said C 1-6 alkyl, C 3-6 alkenyl, C 3-6 alkynyl, aryl, heteroaryl, cycloalkyl and heterocycloalkyl can be optionally substituted by 1, 2 or 3 groups independently selected from halogen, cyano-group, OR a , SR a and NR b R c ;
Y is selected from pyridyl, pyrimidyl, pyridazinyl, pyrazinyl, triazinyl, thiazolyl, isothiazolyl, imidazolyl, oxazolyl, isoxazolyl, triazolyl or pyrazolyl, and can be substituted by 1, 2, or 3 R 4 ;
Z is selected from pyridyl, pyrimidyl, pyridazinyl, pyrazinyl, triazinyl, thiazolyl, isothiazolyl, imidazolyl, oxazolyl, isoxazolyl, triazolyl, pyrazolyl, azotic oxazolyl, pyrindol, pyrrolo-pyrimidyl, pyrazolo-pyridyl, pyrazolo-pyrimidyl, quinolyl, isoquinolyl, quinazolyl, piperazinyl or morpholinyl, and can be substituted by 1, 2, or 3 R 5 ;
R 4 and R 5 are independently selected from halogen, cyano-group, OR a , SR a , NR b R c , C 1-6 alkyl, C 1-6 hydroxyalkyl, C 1-6 haloalkyl, C 1-6 cyanoalkyl, C 2-6 alkenyl, C 2-6 alkynyl, NR b (CO)R d , C(O)NR b R c , NR b S(O) 2 R d , S(O) 2 NR b R c , C(O)R d , C(O)OR a , S(O) 2 R d , cycloalkyl, heterocycloalkyl, aryl, and heteroaryl;
Alternatively, two R 4 or two R 5 groups taken together with the atoms attached to them respectively, can form a cycloalkyl and heterocycloalkyl of 5, 6 or 7-membered ring, and can be optionally substituted by 1, 2 or 3 groups independently selected from halogen, cyano-group, OR a , SR a , NR b R c , C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 hydroxyalkyl, C 1-6 cyanoalkyl, C 2-6 alkenyl and C 2-6 alkynyl;
R a , R b , R c and R d are independently selected from H, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 hydroxyalkyl, C 1-6 cyanoalkyl, C 2-6 alkenyl, C 2-6 alkynyl, aryl, heteroaryl, cycloalkyl, and heterocycloalkyl;
Alternatively, R b and R c taken together with the nitrogen atom attached to them respectively, can form a heterocycloalkyl of 4, 5, 6 or 7-membered ring, and can be optionally substituted by 1, 2 or 3 groups independently selected from halogen, cyano-group, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 hydroxyalkyl, C 1-6 cyanoalkyl, C 2-6 alkenyl, C 2-6 alkynyl, aryl, heteroaryl, cycloalkyl and heterocycloalkyl; and
p is an integer from one to two.
5. The compound or its pharmaceutically acceptable salt or prodrug thereof according to claim 1 , having formula IIb:
wherein:
R 9 and R 10 are independently selected from H, C 1-6 alkyl, C 2-6 hydroxyalkyl, C 2-6 haloalkyl, C 1-6 cyanoalkyl, C(O)NR b R c , C(O)R d , C(O)OR a , S(O) 2 R d , C 3-6 alkenyl, C 3-6 alkynyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl, wherein the said C 1-6 alkyl, C 3-6 alkenyl, C 3-6 alkynyl, aryl, heteroaryl, cycloalkyl and heterocycloalkyl can be optionally substituted by 1, 2 or 3 groups independently selected from halogen, cyano-group, OR a , SR a or NR b R c ;
Alternatively, R 9 and R 10 taken together with the atoms attached to them respectively, can form a cycloalkyl or heterocycloalkyl of 5, 6 or 7-membered ring, and can be optionally substituted by 1, 2 or 3 groups independently selected from halogen, cyano-group, OR a , SR a , NR b R c , C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 hydroxyalkyl, C 1-6 cyanoalkyl, C 2-6 alkenyl, C 2-6 alkynyl, aryl, heteroaryl, cycloalkyl and heterocycloalkyl;
R 11 is H, halogen, cyano-group, OR a , SR a , NR b R c , C 1-6 alkyl, C 1-6 hydroxyalkyl, C 1-6 haloalkyl, C 1-6 cyanoalkyl, C 2-6 alkenyl, C 2-6 alkynyl;
Y is selected from pyridyl, pyrimidyl, pyridazinyl, pyrazinyl, triazinyl, thiazolyl, isothiazolyl, imidazolyl, oxazolyl, isoxazolyl, triazolyl or pyrazolyl, and can be substituted by 1, 2, or 3 R 4 ;
Z is selected from pyridyl, pyrimidyl, pyridazinyl, pyrazinyl, triazinyl, thiazolyl, isothiazolyl, imidazolyl, oxazolyl, isoxazolyl, triazolyl, pyrazolyl, azotic oxazolyl, pyrindol, pyrrolo-pyrimidyl, pyrazolo-pyridyl, pyrazolo-pyrimidyl, quinolyl, isoquinolyl, quinazolyl, piperazinyl or morpholinyl, and can be substituted by 1, 2, or 3 R 5 ;
R 4 and R 5 are independently selected from halogen, cyano-group, OR a , SR a , NR b R c , C 1-6 alkyl, C 1-6 hydroxyalkyl, C 1-6 haloalkyl, C 1-6 cyanoalkyl, C 2-6 alkenyl, C 2-6 alkynyl, NR b (CO)R d , C(O)NR b R c , NR b S(O) 2 R d , S(O) 2 NR b R c , C(O)R d , C(O)OR a , S(O) 2 R d , cycloalkyl, heterocycloalkyl, aryl, and heteroaryl;
Alternatively, two R 4 or two R 5 groups taken together with the atoms attached to them respectively, can form a cycloalkyl or heterocycloalkyl of 5, 6 or 7-membered ring, and can be optionally substituted by 1, 2 or 3 groups independently selected from halogen, cyano-group, OR a , SR a , NR b R c , C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 hydroxyalkyl, C 1-6 cyanoalkyl, C 2-6 alkenyl, and C 2-6 alkynyl;
R a , R b , R c and R d are independently selected from H, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 hydroxyalkyl, C 1-6 cyanoalkyl, C 2-6 alkenyl, C 2-6 alkynyl, aryl, heteroaryl, cycloalkyl, and heterocycloalkyl;
Alternatively, R b and R c taken together with the nitrogen atom attached to them respectively, can form a heterocycloalkyl of 4, 5, 6 or 7-membered ring, and can be optionally substituted by 1, 2 or 3 groups independently selected from halogen, cyano-group, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 hydroxyalkyl, C 1-6 cyanoalkyl, C 2-6 alkenyl, C 2-6 alkynyl, aryl, heteroaryl, cycloalkyl and heterocycloalkyl; and
q is an integer from zero to three.
6. The compound or its pharmaceutically acceptable salt or prodrug thereof according to claim 1 , wherein the said compound is selected from:
1-(4-Methylpiperazin-1-yl)-N-(4-methyl-3-[(4-pyridin-3-ylpyrimidin-2-yl)amino]phenyl)-2,3-dihydro-1H-inden-5-carboxamide;
tert-Butyl 4-{5-[({(4-methyl-3-[(4-pyridin-3-ylpyrimidin-2-yl)amino]phenyl}amino)carbonyl)-2,3-dihydro-1H-inden-1-yl}piperazin-1-carboxylate;
N-(4-Methyl-3-[(4-pyridin-3-ylpyrimidin-2-yl)amino]phenyl)-1-piperazin-1-yl-2,3-dihydro-1H-indene-5-carboxamide;
1-(4-Ethylpiperazin-1-yl)-N-(4-methyl-3-[(4-pyridin-3-ylpyrimidin-2-yl)amino]phenyl)-2,3-dihydro-1H-indene-5-carboxamide;
1-(4-Isopropylpiperazin-1-yl)-N-(4-methyl-3-[(4-pyridin-3-ylpyrimidin-2-yl)amino]phenyl)-2,3-dihydro-1H-indene-5-carboxamide;
1-[4-(2-Hydroxyethyl)piperazin-1-yl]-N-(4-methyl-3-[(4-pyridin-3-ylpyrimidin-2-yl)amino]phenyl)-2,3-dihydro-1H-indene-5-carboxamide;
1-[4-Acetylpiperazin-1-yl)-N-(4-methyl-3-[(4-pyridin-3-ylpyrimidin-2-yl)amino]phenyl)-2,3-dihydro-1H-indene-5-carboxamide;
N-[3-(4,5′-Bipyrimidin-2-ylamino)-4-methylphenyl]-1-(4-methylpiperazin-1-yl)-2,3-dihydro-1H-indene-5-carboxamide;
1-[(3S)-3-(Dimethylamino)pyrrolidin-1-yl]-N-{4-methyl-3-[(4-pyridin-3-ylpyrimidin-2-yl)amino]phenyl}-2,3-dihydro-1H-indene-5-carboxamide;
1-[(3R)-3-(Dimethylamino)pyrrolidin-1-yl]-N-{4-methyl-3-[(4-pyridin-3-ylpyrimidin-2-yl)amino]phenyl}-2,3-dihydro-1H-indene-5-carboxamide;
(1S)-1-(4-Methylpiperazin-1-yl)-N-(4-methyl-3-[(4-pyridin-3-ylpyrimidin-2-yl)amino]phenyl)-2,3-dihydro-1H-indene-5-carboxamide;
(1R)-1-(4-Methylpiperazin-1-yl)-N-(4-methyl-3-[(4-pyridin-3-ylpyrimidin-2-yl)amino]phenyl)-2,3-dihydro-1H-indene-5-carboxamide;
(1S)—N-[3-(4,5′-Bipyrimidin-2-ylamino)-4-methylphenyl]-1-(4-methylpiperazin-1-yl)-2,3-dihydro-1H-indene-5-carboxamide;
(1R)—N-[3-(4,5′-Bipyrimidin-2-ylamino)-4-methylphenyl]-1-(4-methylpiperazin-1-yl)-2,3-dihydro-1H-indene-5-carboxamide;
(1S)-1-(4-Methylpiperazin-1-yl)-N-(4-methyl-3-[(4-pyridin-4-ylpyrimidin-2-yl)amino]phenyl)-2,3-dihydro-1H-indene-5-carboxamide; and
(1S)-1-(4-Methylpiperazin-1-yl)-N-(4-methyl-3-[(4-pyridin-3-ylpyrimidin-2-yl)amino]phenyl)-2,3-dihydro-1H-indene-5-carboxamide sulfate.
7. A pharmaceutical composition, wherein said pharmaceutical composition comprises the compound or pharmaceutically acceptable salt or prodrug of claim 1 , and at least one pharmaceutically acceptable carrier.