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US 2012/0238564 A1Published application
Imidazo pyrazines
AssigneeHoffmann-La Roche Inc.
InventorsKin-Chun Luk, Michael Soth
Life of this patent
Estimating the term…
Abstract
Compounds of formula and pharmaceutically acceptable salts thereof are described, as well as the pharmaceutical compositions containing said compounds and their pharmaceutically acceptable salts, and the use of said compounds and pharmaceutical compositions for the treatment, control or amelioration of AML.
Claims32
A compound of formula I
- wherein
- X is selected from CH or N,
- R1 and R2 are independently selected from the group consisting of
- (a) H,
- (b) C1-4 alkyl,
- (c) C1-4 alkyl substituted with up to 3 groups selected from cycloalkyl, heterocycle, OR5, NR5R6, SO2R7 or CN,
- (d) heterocycle,
- (e) heterocycle substituted with up to three groups selected from C1-4 alkyl, OR8, NR8R9 or CN,
- (f) cycloalkyl, and
- (g) cycloalkyl substituted with up to three groups selected from C1-4 alkyl, OR8, NR8R9 or CN;
- or
- alternatively, NR1R2 together can be a heterocycle that optionally may be substituted with C1-4 alkyl;
- R3 is selected from the group consisting of
- (a) C1-6 alkyl
- (b) C1-6 alkyl substituted with up to 3 groups selected from
- aryl,
- aryl substituted with Cl, F, CH3, or CF3,
- heteroaryl,
- cycloalkyl,
- heterocycle,
- OH,
- OCH3,
- NR8R9, and
- CN;
- (c) aryl,
- (d) aryl substituted with Cl, F, C1-4 alkyl or CF3,
- (e) heteroaryl,
- (f) cycloalkyl optionally substituted with OR5, and
- (g) heterocycle;
- R4, R8 and R9 are independently selected from the group consisting of
- (a) H, and
- (b) C1-4 alkyl;
- or
- alternatively, NR3R4 together can be a heterocycle that optionally is substituted with C1-4 alkyl;
- R5 and R6 are independently selected from the group consisting of
- (a) H, and
- (b) C1-4 alkyl;
- and
- R7 is selected from the group
- (a) C1-4 alkyl, and
- (b) cycloalkyl;
- or a pharmaceutically acceptable salt thereof.
39 more elements
A compound selected from the group comprising:
- Isopropyl-[3-(2-phenylamino-pyrimidin-4-yl)-imidazo[1,2-a]pyrazin-8-yl]-amine;
- 2-[3-(2-Phenylamino-pyrimidin-4-yl)-imidazo[1,2-a]pyrazin-8-ylamino]-ethanol;
- (2-Methanesulfonyl-ethyl)-{3-[2-(tetrahydro-pyran-4-ylamino)-pyrimidin-4-yl]-imidazo[1,2-a]pyrazin-8-yl}-amine;
- (2-Methanesulfonyl-ethyl)-[3-(2-morpholin-4-yl-pyrimidin-4-yl)-imidazo[1,2-a]pyrazin-8-yl]-amine;
- [3-(2-Isopropylamino-pyrimidin-4-yl)-imidazo[1,2-a]pyrazin-8-yl]-(2-methanesulfonyl-ethyl)-amine;
- 4-[4-(8-Isopropylamino-imidazo[1,2-a]pyrazin-3-yl)-pyrimidin-2-ylamino]-cyclohexanol;
- Isopropyl-{3-[2-(tetrahydro-pyran-4-ylamino)-pyrimidin-4-yl]-imidazo[1,2-a]pyrazin-8-yl}-amine;
- Isopropyl-[3-(2-morpholin-4-yl-pyrimidin-4-yl)-imidazo[1,2-a]pyrazin-8-yl]-amine;
- Methyl-[3-(2-phenylamino-pyrimidin-4-yl)-imidazo[1,2-a]pyrazin-8-yl]-amine;
- Methyl-[3-(2-morpholin-4-yl-pyrimidin-4-yl)-imidazo[1,2-a]pyrazin-8-yl]-amine;
- and
- Piperidin-4-yl-{3-[2-(tetrahydro-pyran-4-ylamino)-pyrimidin-4-yl]-imidazo[1,2-a]pyrazin-8-yl}-amine;
- or a pharmaceutically acceptable salt of any of the foregoing compounds.
10 more elements
A compound selected from the group comprising:
- [3-(2-Morpholin-4-yl-pyrimidin-4-yl)-imidazo[1,2-a]pyrazin-8-yl]-piperidin-4-yl-amine;
- [3-(2-Isopropylamino-pyrimidin-4-yl)-imidazo[1,2-a]pyrazin-8-yl]-piperidin-4-yl-amine;
- Isopropyl-[3-(2-isopropylamino-pyrimidin-4-yl)-imidazo[1,2-a]pyrazin-8-yl]-amine;
- [3-(2-Methylamino-pyrimidin-4-yl)-imidazo[1,2-a]pyrazin-8-yl]-piperidin-4-yl-amine;
- 4-{4-[8-(2-Methanesulfonyl-ethylamino)-imidazo[1,2-a]pyrazin-3-yl]-pyrimidin-2-ylamino}-cyclohexanol;
- 2-{3-[2-(Tetrahydro-pyran-4-ylamino)-pyrimidin-4-yl]-imidazo[1,2-a]pyrazin-8-ylamino}-ethanol;
- 2-[3-(2-Morpholin-4-yl-pyrimidin-4-yl)-imidazo[1,2-a]pyrazin-8-ylamino]-ethanol;
- 2-[3-(2-Isopropylamino-pyrimidin-4-yl)-imidazo[1,2-a]pyrazin-8-ylamino]-ethanol;
- 2-[3-(2-Methylamino-pyrimidin-4-yl)-imidazo[1,2-a]pyrazin-8-ylamino]-ethanol;
- Isopropyl-[3-(2-methylamino-pyrimidin-4-yl)-imidazo[1,2-a]pyrazin-8-yl]-amine;
- and
- (2-Methanesulfonyl-ethyl)-[3-(2-methylamino-pyrimidin-4-yl)-imidazo[1,2-a]pyrazin-8-yl]-amine;
- or a pharmaceutically acceptable salt of any of the foregoing compounds.
10 more elements
A compound selected from the group comprising:
- Methyl-{3-[2-(tetrahydro-pyran-4-ylamino)-pyrimidin-4-yl]-imidazo[1,2-a]pyrazin-8-yl}-amine;
- Methyl-[3-(2-methylamino-pyrimidin-4-yl)-imidazo[1,2-a]pyrazin-8-yl]-amine;
- N1-{4-[8-(4-Methyl-piperazin-1-yl)-imidazo[1,2-a]pyrazin-3-yl]-pyrimidin-2-yl}-1-phenyl-ethane-1,2-diamine;
- hydrochloride;
- N1-{4-[8-(4-Methyl-piperazin-1-yl)-imidazo[1,2-a]pyrazin-3-yl]-pyrimidin-2-yl}-1-phenyl-propane-1,3-diamine;
- hydrochloride;
- N1-{6-[8-(4-Methyl-piperazin-1-yl)-imidazo[1,2-a]pyrazin-3-yl]-pyridin-2-yl}-1-phenyl-ethane-1,2-diamine;
- hydrochloride;
- Benzyl-{6-[8-(4-methyl-piperazin-1-yl)-imidazo[1,2-a]pyrazin-3-yl]-pyridin-2-yl}-amine;
- Benzyl-{4-[8-(4-methyl-piperazin-1-yl)-imidazo[1,2-a]pyrazin-3-yl]-pyrimidin-2-yl}-amine;
- (2-Chloro-benzyl)-{4-[8-(4-methyl-piperazin-1-yl)-imidazo[1,2-a]pyrazin-3-yl]-pyrimidin-2-yl}-amine;
- hydrochloride;
- (4-Chloro-benzyl)-{4-[8-(4-methyl-piperazin-1-yl)-imidazo[1,2-a]pyrazin-3-yl]-pyrimidin-2-yl}-amine;
- hydrochloride;
- N1-{6-[8-(4-Methyl-piperazin-1-yl)-imidazo[1,2-a]pyrazin-3-yl]-pyridin-2-yl}-1-phenyl-propane-1,3-diamine;
- hydrochloride;
- and
- {4-[8-(4-Methyl-piperazin-1-yl)-imidazo[1,2-a]pyrazin-3-yl]-pyrimidin-2-yl}-thiophen-3-ylmethyl-amine;
- or a pharmaceutically acceptable salt of any of the foregoing compounds.
16 more elements
A compound selected from the group comprising:
- 1-(3-Chloro-phenyl)-N-1-{4-[8-(4-methyl-piperazin-1-yl)-imidazo[1,2-a]pyrazin-3-yl]-pyrimidin-2-yl}-propane-1,3-diamine;
- hydrochloride;
- {4-[8-(4-Methyl-piperazin-1-yl)-imidazo[1,2-a]pyrazin-3-yl]-pyrimidin-2-yl}-thiophen-2-ylmethyl-amine;
- hydrochloride;
- (2-Chloro-benzyl)-{6-[8-(4-methyl-piperazin-1-yl)-imidazo[1,2-a]pyrazin-3-yl]-pyridin-2-yl}-amine;
- hydrochloride;
- (3-Chloro-benzyl)-{4-[8-(4-methyl-piperazin-1-yl)-imidazo[1,2-a]pyrazin-3-yl]-pyrimidin-2-yl}-amine;
- hydrochloride;
- N-{3-[2-(3-Chloro-benzylamino)-pyrimidin-4-yl]-imidazo[1,2-a]pyrazin-8-yl}-cyclohexane-1,4-diamine;
- hydrochloride;
- N-[3-(2-Benzylamino-pyrimidin-4-yl)-imidazo[1,2-a]pyrazin-8-yl]-cyclohexane-1,4-diamine;
- hydrochloride;
- N1-{4-[8-(4-Methyl-piperazin-1-yl)-imidazo[1,2-a]pyrazin-3-yl]-pyrimidin-2-yl}-1-thiophen-3-yl-propane-1,3-diamine;
- hydrochloride;
- (4-Chloro-benzyl)-{6-[8-(4-methyl-piperazin-1-yl)-imidazo[1,2-a]pyrazin-3-yl]-pyridin-2-yl}-amine;
- hydrochloride;
- [3-(2-Benzylamino-pyrimidin-4-yl)-imidazo[1,2-a]pyrazin-8-yl]-(2-morpholin-4-yl-ethyl)-amine;
- hydrochloride;
- N-[3-(6-Benzylamino-pyridin-2-yl)-imidazo[1,2-a]pyrazin-8-yl]-cyclohexane-1,4-diamine;
- hydrochloride;
- N1-{4-[8-(4-Methyl-piperazin-1-yl)-imidazo[1,2-a]pyrazin-3-yl]-pyrimidin-2-yl}-1-thiophen-3-yl-ethane-1,2-diamine;
- hydrochloride;
- N-{3-[2-(3-Amino-1-phenyl-propylamino)-pyrimidin-4-yl]-imidazo[1,2-a]pyrazin-8-yl}-cyclohexane-1,4-diamine;
- hydrochloride;
- and
- N-{3-[2-(2-Amino-1-phenyl-ethylamino)-pyrimidin-4-yl]-imidazo[1,2-a]pyrazin-8-yl}-cyclohexane-1,4-diamine;
- hydrochloride;
- or a pharmaceutically acceptable salt of any of the foregoing compounds.
25 more elements
A compound selected from the group comprising:
- 1-(3-Chloro-phenyl)-N-1-{4-[8-(4-methyl-piperazin-1-yl)-imidazo[1,2-a]pyrazin-3-yl]-pyrimidin-2-yl}-ethane-1,2-diamine;
- hydrochloride;
- N-{3-[6-(2-Amino-1-phenyl-ethylamino)-pyridin-2-yl}-imidazo[1,2-a]pyrazin-8-yl]-cyclohexane-1,4-diamine;
- hydrochloride;
- N-{3-[6-(3-Amino-1-phenyl-propylamino)-pyridin-2-yl]-imidazo[1,2-a]pyrazin-8-yl}-cyclohexane-1,4-diamine;
- hydrochloride;
- N-{3-[6-(3-Chloro-benzylamino)-pyridin-2-yl]-imidazo[1,2-a]pyrazin-8-yl}-cyclohexane-1,4-diamine;
- hydrochloride;
- N-{3-[2-(2-Chloro-benzylamino)-pyrimidin-4-yl]-imidazo[1,2-a]pyrazin-8-yl}-cyclohexane-1,4-diamine;
- hydrochloride;
- N-(3-{6-[(Thiophen-3-ylmethyl)-amino]-pyridin-2-yl}-imidazo[1,2-a]pyrazin-8-yl)-cyclohexane-1,4-diamine;
- hydrochloride;
- N-{3-[6-(2-Chloro-benzylamino)-pyridin-2-yl]-imidazo[1,2-a]pyrazin-8-yl}-cyclohexane-1,4-diamine;
- hydrochloride;
- N-{3-[6-(4-Chloro-benzylamino)-pyridin-2-yl]-imidazo[1,2-a]pyrazin-8-yl}-cyclohexane-1,4-diamine;
- hydrochloride;
- N-(3-{6-[(Thiophen-2-ylmethyl)-amino]-pyridin-2-yl}-imidazo[1,2-a]pyrazin-8-yl)-cyclohexane-1,4-diamine;
- hydrochloride;
- {3-[2-(2-Chloro-benzylamino)-pyrimidin-4-yl]-imidazo[1,2-a]pyrazin-8-yl}-(2-morpholin-4-yl-ethyl)-amine;
- hydrochloride;
- {3-[2-(3-Chloro-benzylamino)-pyrimidin-4-yl]-imidazo[1,2-a]pyrazin-8-yl}-(2-morpholin-4-yl-ethyl)-amine;
- hydrochloride;
- 1-(3-Chloro-phenyl)-N-1-{6-[8-(2-morpholin-4-yl-ethylamino)-imidazo[1,2-a]pyrazin-3-yl]-pyridin-2-yl}-propane-1,3-diamine hydrochloride;
- and
- 1-(3-Chloro-phenyl)-N-1-{6-[8-(2-morpholin-4-yl-ethylamino)-imidazo[1,2-a]pyrazin-3-yl]-pyridin-2-yl}-ethane-1,2-diamine hydrochloride;
- or a pharmaceutically acceptable salt of any the foregoing compounds.
23 more elements
Dependencies are inferred from the claim text.