IP Library › Granted Patent US 8,586,566
Granted Patent B2
US 8,586,566 · App. 13/311,106 · Granted Nov 19, 2013

Unsaturated heterocyclic derivatives

Inventors: Yihan Wang (Newton, MA); Wei-Sheng Huang (Acton, MA); Rajeswari Sundaramoorthi (Chennai, IN); Xiaotian Zhu (Newton, MA); R. Mathew Thomas (Sharon, MA); William C. Shakespeare (Southborough, MA); David C. Dalgarno (Brookline, MA); Tomi K. Sawyer (Southborough, MA)
Assignee: ARIAD Pharmaceuticals, Inc.
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Quick Facts
Patent No.
US 8,586,566
App. No.
13/311,106
Granted
Nov 19, 2013
Kind
B2
Abstract

This invention relates to specific compounds and their pharmaceutically acceptable salts of the general formula: wherein Q is —CR═CR′— and Ring A is an aryl, heteroaryl or heterocyclic ring or ring system. This invention also relates to pharmaceutical compositions comprising such specific compounds or their pharmaceutically acceptable salts and a pharmaceutically acceptable carrier or adjuvant.

Claims (291)

1. A compound selected from the group consisting of:

(E)-N-(4-methyl-3-(2-(6-(methylamino)-9H-purin-9-yl)vinyl)phenyl)-3-(trifluoromethyl)benzamide;

N-(4-Methyl-3-(2-(6-(methylamino)-9H-purin-9-yl)ethyl)phenyl)-(trifluoromethyl)benzamide;

(E)-N-(3-(2-(6-(4-(Dimethylphosphoryl)phenylamino)-9H-purin-9-yl)vinyl)-4-methylphenyl)-3-(trifluoromethyl)benzamide;

(E)-3-(2-(6-(Cyclopropylamino)-9H-purin-9-yl)vinyl)-4-methyl-N-(3-(4-methyl-1-imidazol-1-yl)-5-(trifluoromethyl)phenyl)benzamide;

(E)-3-(2-(6-(Cyclopropylamino)-9H-purin-9-yl)vinyl)-4-methyl-N-(3-(trifluoromethyl)phenyl)benzamide;

(E)-1-(3-(2-(6-(Cyclopropylamino)-9H-purin-9-yl)vinyl)-4-methylphenyl)-3-(3-(trifluoromethyl)phenyl)urea;

(E)-3-(2-(6-(Cyclopropylamino)-9H-purin-9-yl)vinyl)-4-methyl-N-(4-(trifluoromethyl)pyridin-2-yl)benzamide;

(E)-3-(2-(6-Amino-9H-purin-9-yl)vinyl)-4-methyl-N-(3-(4-methyl-1H-imidazol-1-yl)-5-(trifluoromethyl)phenyl)benzamide;

(E)-N-(4-Methyl-3-(2-(6-(pyridin-3-ylamino)-9H-purin-9-yl)vinyl)phenyl)-3-(trifluoromethyl)benzamide;

(E)-9-(2-(2-Chloro-4-methylpyridin-3-yl)vinyl)-N-(4-(dimethylphosphoryl)phenyl)-9H-purin-6-amine;

(E)-9-(2,6-dimethylstyryl)-N-(4-(dimethylphosphoryl)phenyl)-9H-purin-6-amine;

(E)-9-(2-chloro-6-methylstyryl)-N-(4-(dimethylphosphoryl)phenyl)-9H-purin-6-amine;

(E)-9-(2-chloro-6-fluorostyryl)-N-(4-(dimethylphosphoryl)phenyl)-9H-purin-6-amine;

(E)-9-(2-methyl-6-ethylstyryl)-N-(4-(dimethylphosphoryl)phenyl)-9H-purin-6-amine;

(E)-9-(2-methyl-6-aminostyryl)-N-(4-(dimethylphosphoryl)phenyl)-9H-purin-6-amine;

(E)-9-(2-methyl-6-aminostyryl)-N-(4-(dimethylphosphoryl)phenyl)-9H-purin-6-amine;

(E)-9-(2-(1H-indol-4-yl)vinyl)-N-(4-(dimethylphosphoryl)phenyl)-9H-purin-6-amine;

(E)-4-(2-(6-(4-(dimethylphosphoryl)phenylamino)-9H-purin-9-yl)vinyl)indolin-2-one;

(E)-9-(2-(1H-indazol-4-yl)vinyl)-N-(4-(dimethylphosphoryl)phenyl)-9H-purin-6-amine;

(E)-N-(4-(dimethylphosphoryl)phenyl)-9-(2-(5-methyl-1H-indazol-4-yl)vinyl)-9H-purin-6-amine;

(E)-N-(4-(dimethylphosphoryl)phenyl)-9-(2-(5-methyl-1H-indol-4-yl)vinyl)-9H-purin-6-amine;

(E)-9-(2,6-dimethylstyryl)-N-(4-(dipropylphosphoryl)phenyl)-2-isopropyl-9H-purin-6-amine;

(E)-N-(4-(dipropylphosphoryl)phenyl)-2-isopropyl-9-styryl-9H-purin-6-amine;

N-(4-(Dipropylphosphoryl)phenyl)-2-isopropyl-9-(2-methylprop-1-enyl)-9H-purin-6-amine;

9-(Cyclohexylidenemethyl)-N-(4-(dipropylphosphoryl)phenyl)-2-isopropyl-9H-purin-6-amine;

(E)-9-(2-cyclopropylvinyl)-N-(4-(dipropylphosphoryl)phenyl)-2-isopropyl-9H-purin-6-amine;

(E)-9-(2,6-dimethylstyryl)-N-(4-(dimethylphosphoryl)phenyl)-2-morpholino-9H-purin-6-amine;

(E)-9-(2,6-dimethylstyryl)-N 6 -(4-(dimethylphosphoryl)phenyl)-9H-purine-2,6-diamine;

(E)-2-(4-(9-(2,6-dimethylstyryl)-6-(4-(dimethylphosphoryl)phenylamino)-9H-purin-2-yl)piperazin-1-yl)ethanol;

(E)-9-(2,6-dimethylstyryl)-N 6 -(4-(dimethylphosphoryl)phenyl)-N 2 ,N 2 -dimethyl-9H-purine-2,6-diamine;

(E)-9-(2,6-dimethylstyryl)-N-(4-(dimethylphosphoryl)phenyl)-2-(pyrrolidin-1-yl)-9H-purin-6-amine;

(E)-9-(2,6-dimethylstyryl)-N 2 -(2-(dimethylamino)ethyl)-N 6 -(4-(dimethylphosphoryl)phenyl)-9H-purine-2,6-diamine;

(E)-9-(2,6-dimethylstyryl)-N 2 -(2-(dimethylamino)ethyl)-N 6 -(4-(dimethylphosphoryl)phenyl)-N 2 -ethyl-9H-purine-2,6-diamine;

(E)-9-(2,6-dimethylstyryl)-N 6 -(4-(dimethylphosphoryl)phenyl)-N 2 -(2-methoxyethyl)-9H-purine-2,6-diamine;

(E)-9-(2,6-dimethylstyryl)-N 2 -(4-aminocyclohexyl)-N 6 -(4-(dimethylphosphoryl)phenyl)-9H-purine-2,6-diamine;

(E)-9-(2,6-dimethylstyryl)-N-(4-(dimethylphosphoryl)phenyl)-2-(piperazin-1-yl)-9H-purin-6-amine;

(E)-9-(2,6-dimethylstyryl)-N 2 -cyclopropyl-N 6 -(4-(dimethylphosphoryl)phenyl)-9H-purine-2,6-diamine;

(R,E)-2-(9-(2,6-dimethylstyryl)-6-(4-(dipropylphosphoryl)phenylamino)-9H-purin-2-ylamino)-3-methylbutan-1-ol;

(E)-9-(2,6-dimethylstyryl)-2-(4-(aminomethyl)piperidin-1-yl)-N-(4-(dipropylphosphoryl)phenyl)-9H-purin-6-amine;

(E)-9-(2,6-dimethylstyryl)-N-(4-(dimethylphosphoryl)phenyl)-2-(1H-imidazol-1-yl)-9H-purin-6-amine;

(E)-9-(2,6-dimethylstyryl)-N-(4-(dimethylphosphoryl)phenyl)-2-(4-methyl-1H-imidazol-1-yl)-9H-purin-6-amine;

(E)-9-(2,6-dimethylstyryl)-N-(4-(dimethylphosphoryl)phenyl)-2-methoxy-9H-purin-6-amine;

(E)-9-(2,6-dimethylstyryl)-2-(2-(dimethylamino)ethoxy)-N-(4-(dipropylphosphoryl)phenyl)-9H-purin-6-amine;

(E)-9-(2,6-dimethylstyryl)-N-(4-(dimethylphosphoryl)phenyl)-2-(2-methoxyethoxy)-9H-purin-6-amine;

(E)-9-(2,6-dimethylstyryl)-N-(4-(dimethylphosphoryl)phenyl)-2-(tetrahydro-2H-pyran-4-yloxy)-9H-purin-6-amine;

(E)-9-(2,6-dimethylstyryl)-N-(4-(dimethylphosphoryl)phenyl)-2-(tetrahydrofuran-3-yloxy)-9H-purin-6-amine;

(E)-9-(2,6-dimethylstyryl)-2-(cyclopentyloxy)-N-(4-(dimethylphosphoryl)phenyl)-9H-purin-6-amine;

(E)-9-(2,6-dimethylstyryl)-N-(4-(dimethylphosphoryl)phenyl)-2-(1-methylpiperidin-4-yloxy)-9H-purin-6-amine;

(E)-9-(2,6-dimethylstyryl)-N-(4-(dimethylphosphoryl)phenyl)-2-(pyridin-3-yloxy)-9H-purin-6-amine;

(E)-9-(2,6-dimethylstyryl)-N-(4-(dimethylphosphoryl)phenyl)-2-(methylthio)-9H-purin-6-amine;

(E)-9-(2,6-dimethyl styryl)-N-(4-(dimethylphosphoryl)phenyl)-2-(methylsulfonyl)-9H-purin-6-amine;

(E)-9-(2,6-dimethylstyryl)-2-isopropyl-N-(4-(dimethylphosphoryl)phenyl)-9H-purin-6-amine;

(E)-9-(2,6-dimethylstyryl)-2-sec-butyl-N-(4-(dimethylphosphoryl)phenyl)-9H-purin-6-amine;

(E)-9-(2,6-dimethylstyryl)-2-cyclohexyl-N-(4-(dimethylphosphoryl)phenyl)-9H-purin-6-amine;

(E)-9-(2,6-dimethylstyryl)-2-cyclopentyl-N-(4-(dimethylphosphoryl)phenyl)-9H-purin-6-amine;

(E)-9-(2,6-dimethylstyryl)-N-(4-(dimethylphosphoryl)phenyl)-2-isobutyl-9H-purin-6-amine;

(E)-9-(2,6-dimethylstyryl)-N-(4-(dimethylphosphoryl)phenyl)-2-(pentan-3-yl)-9H-purin-6-amine;

(E)-3-(9-(2,6-dimethylstyryl)-6-(4-(dimethylphosphoryl)phenylamino)-9H-purin-2-yl)propanenitrile;

(E)-9-(2,6-dimethylstyryl)-2-(5-chlorothiophen-2-yl)-N-(4-(dimethylphosphoryl)phenyl)-9H-purin-6-amine;

(E)-9-(2,6-dimethylstyryl)-N-(4-(dimethylphosphoryl)phenyl)-2-(thiophen-2-yl)-9H-purin-6-amine;

(E)-9-(2,6-dimethylstyryl)-N-(4-(dimethylphosphoryl)phenyl)-2-(5-methylpyridin-2-yl)-9H-purin-6-amine;

(E)-9-(2,6-dimethylstyryl)-N-(4-(dimethylphosphoryl)phenyl)-2-(4-methylpyridin-2-yl)-9H-purin-6-amine;

(E)-N-(4-methyl-3-(2-(6-(2-N,N-dimethylaminoethylamino)-9H-purin-9-yl)vinyl)phenyl)-3-(trifluoromethyl)benzamide;

(E)-N-(4-methyl-3-(2-(6-(cyclopropylamino)-9H-purin-9-yl)vinyl)phenyl)-3-(trifluoromethyl)benzamide;

(E)-3-(2-(6-(Phenylamino)-9H-purin-9-yl)vinyl)-4-methyl-N-(3-(4-methyl-1-imidazol-1-yl)-5-(trifluoromethyl)phenyl)benzamide;

(E)-N-(4-Methyl-3-(2-(6-(pyridin-4-ylamino)-9H-purin-9-yl)vinyl)phenyl)-3-(trifluoromethyl)benzamide;

(E)-N-(4-Methyl-3-(2-(6-(pyridin-2-ylamino)-9H-purin-9-yl)vinyl)phenyl)-3-(trifluoromethyl)benzamide;

(E)-N-(4-methyl-3-(2-(6-(3-N,N-dimethylaminopropylamino)-9H-purin-9-yl)vinyl)phenyl)-3-(trifluoromethyl)benzamide;

(E)-3-(2-(6-(4-(Dimethylphosphoryl)phenylamino)-9H-purin-9-yl)vinyl)-4-methyl-N-(3-(trifluoromethyl)phenyl)benzamide;

(E)-3-(2-(6-(4-(Dimethylphosphoryl)phenylamino)-9H-purin-9-yl)vinyl)-4-methyl-N-(5-tert-butylisoxazol-3-yl)benzamide;

(E)-N-(4-Methyl-3-(2-(6-(pyrimidin-4-ylamino)-9H-purin-9-yl)vinyl)phenyl)-3-(trifluoromethyl)benzamide;

(E)-N-(4-methyl-3-(2-(6-(1-methylpiperidin-4-ylamino)-9H-purin-9-yl)vinyl)phenyl)-3-(trifluoromethyl)benzamide;

(E)-3-(2-(6-Cyclopropylamino)-9H-purin-9-yl)vinyl)-4-methyl-N-(5-tert-butylisoxazol-3-yl)benzamide;

(E)-3-(2-(6-Cyclopropylamino)-9H-purin-9-yl)vinyl)-4-methyl-N-(3-tert-butyl-1-methylpyrazol-5-yl)benzamide;

(E)-3-(2-(6-Cyclopropylamino)-9H-purin-9-yl)vinyl)-4-methyl-N-(3-tert-butylpyrazol-5-yl)benzamide;

(E)-3-(2-(6-Cyclopropylamino)-9H-purin-9-yl)vinyl)-4-methyl-N-(3-tert-butylphenyl)benzamide;

(E)-3-(2-(6-Cyclopropylamino)-9H-purin-9-yl)vinyl)-4-methyl-N-(4-chloro-3-trifluoromethylphenyl)benzamide;

(E)-3-(2-(6-Cyclopropylamino)-9H-purin-9-yl)vinyl)-4-methyl-N-(2-fluoro-5-trifluoromethylphenyl)benzamide;

(E)-3-(2-(6-Amino-9H-purin-9-yl)vinyl)-4-methyl-N-(4-(trifluoromethyl)pyridin-2-yl)benzamide;

(E)-N-(3-(2-(6-(4-(Dimethylphosphoryl)phenylamino)-9H-purin-9-yl)vinyl)-4-methylphenyl)nicotinamide;

(E)-N-(3-(2-(6-(4-(Dimethylphosphoryl)phenylamino)-9H-purin-9-yl)vinyl)-4-methylphenyl)-5-cyclopropylisoxazole-3-carboxamide;

(E)-N-(3-(2-(6-(4-cyanophenylamino)-9H-purin-9-yl)vinyl)-4-methylphenyl)-3-(trifluoromethyl)benzamide;

(E)-3-(2-(6-(Cyclopropylamino)-9H-purin-9-yl)vinyl)-4-methyl-N-(3-isopropylphenyl)benzamide; and

(E)-3-(2-(6-(Cyclopropylamino)-9H-purin-9-yl)vinyl)-4-methyl-N-(4-methylpyridin-2-yl)benzamide,

or a pharmaceutically acceptable salt thereof.

2. A compound according to claim 1 selected from the group consisting of:

(E)-N-(4-methyl-3-(2-(6-(methylamino)-9H-purin-9-yl)vinyl)phenyl)-3-(trifluoromethyl)benzamide;

N-(4-Methyl-3-(2-(6-(methylamino)-9H-purin-9-yl)ethyl)phenyl)-(trifluoromethyl)benzamide;

(E)-N-(3-(2-(6-(4-(Dimethylphosphoryl)phenylamino)-9H-purin-9-yl)vinyl)-4-methylphenyl)-3-(trifluoromethyl)benzamide;

(E)-3-(2-(6-(Cyclopropylamino)-9H-purin-9-yl)vinyl)-4-methyl-N-(3-(4-methyl-1-imidazol-1-yl)-5-(trifluoromethyl)phenyl)benzamide; and

(E)-3-(2-(6-(Cyclopropylamino)-9H-purin-9-yl)vinyl)-4-methyl-N-(3-(trifluoromethyl)phenyl)benzamide,

or a pharmaceutically acceptable salt thereof.

3. A compound according to claim 1 selected from the group consisting of:

(E)-1-(3-(2-(6-(Cyclopropylamino)-9H-purin-9-yl)vinyl)-4-methylphenyl)-3-(3-(trifluoromethyl)phenyl)urea;

(E)-3-(2-(6-(Cyclopropylamino)-9H-purin-9-yl)vinyl)-4-methyl-N-(4-(trifluoromethyl)pyridin-2-yl)benzamide;

(E)-3-(2-(6-Amino-9H-purin-9-yl)vinyl)-4-methyl-N-(3-(4-methyl-1H-imidazol-1-yl)-5-(trifluoromethyl)phenyl)benzamide;

(E)-N-(4-Methyl-3-(2-(6-(pyridin-3-ylamino)-9H-purin-9-yl)vinyl)phenyl)-3-(trifluoromethyl)benzamide; and

(E)-9-(2-(2-Chloro-4-methylpyridin-3-yl)vinyl)-N-(4-(dimethylphosphoryl)phenyl)-9H-purin-6-amine,

or a pharmaceutically acceptable salt thereof.

4. A compound according to claim 1 selected from the group consisting of:

(E)-9-(2,6-dimethylstyryl)-N-(4-(dimethylphosphoryl)phenyl)-9H-purin-6-amine;

(E)-9-(2-chloro-6-methylstyryl)-N-(4-(dimethylphosphoryl)phenyl)-9H-purin-6-amine;

(E)-9-(2-chloro-6-fluorostyryl)-N-(4-(dimethylphosphoryl)phenyl)-9H-purin-6-amine;

(E)-9-(2-methyl-6-ethylstyryl)-N-(4-(dimethylphosphoryl)phenyl)-9H-purin-6-amine; and

(E)-9-(2-methyl-6-aminostyryl)-N-(4-(dimethylphosphoryl)phenyl)-9H-purin-6-amine,

or a pharmaceutically acceptable salt thereof.

5. A compound according to claim 1 selected from the group consisting of:

(E)-9-(2-methyl-6-aminostyryl)-N-(4-(dimethylphosphoryl)phenyl)-9H-purin-6-amine;

(E)-9-(2-(1H-indol-4-yl)vinyl)-N-(4-(dimethylphosphoryl)phenyl)-9H-purin-6-amine;

(E)-4-(2-(6-(4-(dimethylphosphoryl)phenylamino)-9H-purin-9-yl)vinyl)indolin-2-one;

(E)-9-(2-(1H-indazol-4-yl)vinyl)-N-(4-(dimethylphosphoryl)phenyl)-9H-purin-6-amine; and

(E)-N-(4-(dimethylphosphoryl)phenyl)-9-(2-(5-methyl-1H-indazol-4-yl)vinyl)-9H-purin-6-amine,

or a pharmaceutically acceptable salt thereof.

6. A compound according to claim 1 selected from the group consisting of:

(E)-N-(4-(dimethylphosphoryl)phenyl)-9-(2-(5-methyl-1H-indol-4-yl)vinyl)-9H-purin-6-amine;

(E)-9-(2,6-dimethylstyryl)-N-(4-(dipropylphosphoryl)phenyl)-2-isopropyl-9H-purin-6-amine;

(E)-N-(4-(dipropylphosphoryl)phenyl)-2-isopropyl-9-styryl-9H-purin-6-amine;

N-(4-(Dipropylphosphoryl)phenyl)-2-isopropyl-9-(2-methylprop-1-enyl)-9H-purin-6-amine; and

9-(Cyclohexylidenemethyl)-N-(4-(dipropylphosphoryl)phenyl)-2-isopropyl-9H-purin-6-amine,

or a pharmaceutically acceptable salt thereof.

7. A compound according to claim 1 selected from the group consisting of:

(E)-9-(2-cyclopropylvinyl)-N-(4-(dipropylphosphoryl)phenyl)-2-isopropyl-9H-purin-6-amine;

(E)-9-(2,6-dimethyl styryl)-N-(4-(dimethylphosphoryl)phenyl)-2-morpholino-9H-purin-6-amine;

(E)-9-(2,6-dimethylstyryl)-N 6 -(4-(dimethylphosphoryl)phenyl)-9H-purine-2,6-diamine;

(E)-2-(4-(9-(2,6-dimethylstyryl)-6-(4-(dimethylphosphoryl)phenylamino)-9H-purin-2-yl)piperazin-1-yl)ethanol; and

(E)-9-(2,6-dimethylstyryl)-N 6 -(4-(dimethylphosphoryl)phenyl)-N 2 ,N 2 -dimethyl-9H-purine-2,6-diamine,

or a pharmaceutically acceptable salt thereof.

8. A compound according to claim 1 selected from the group consisting of:

(E)-9-(2,6-dimethylstyryl)-N-(4-(dimethylphosphoryl)phenyl)-2-(pyrrolidin-1-yl)-9H-purin-6-amine;

(E)-9-(2,6-dimethylstyryl)-N 2 -(2-(dimethylamino)ethyl)-N 6 -(4-(dimethylphosphoryl)phenyl)-9H-purine-2,6-diamine;

(E)-9-(2,6-dimethylstyryl)-N 2 -(2-(dimethylamino)ethyl)-N 6 -(4-(dimethylphosphoryl)phenyl)-N 2 -ethyl-9H-purine-2,6-diamine;

(E)-9-(2,6-dimethylstyryl)-N 6 -(4-(dimethylphosphoryl)phenyl)-N 2 -(2-methoxyethyl)-9H-purine-2,6-diamine; and

(E)-9-(2,6-dimethylstyryl)-N 2 -(4-aminocyclohexyl)-N 6 -(4-(dimethylphosphoryl)phenyl)-9H-purine-2,6-diamine,

or a pharmaceutically acceptable salt thereof.

9. A compound according to claim 1 selected from the group consisting of:

(E)-9-(2,6-dimethylstyryl)-N-(4-(dimethylphosphoryl)phenyl)-2-(piperazin-1-yl)-9H-purin-6-amine;

(E)-9-(2,6-dimethylstyryl)-N 2 -cyclopropyl-N 6 -(4-(dimethylphosphoryl)phenyl)-9H-purine-2,6-diamine;

(R,E)-2-(9-(2,6-dimethylstyryl)-6-(4-(dipropylphosphoryl)phenylamino)-9H-purin-2-ylamino)-3-methylbutan-1-ol;

(E)-9-(2,6-dimethylstyryl)-2-(4-(aminomethyl)piperidin-1-yl)-N-(4-(dipropylphosphoryl)phenyl)-9H-purin-6-amine; and

(E)-9-(2,6-dimethylstyryl)-N-(4-(dimethylphosphoryl)phenyl)-2-(1H-imidazol-1-yl)-9H-purin-6-amine,

or a pharmaceutically acceptable salt thereof.

10. A compound according to claim 1 selected from the group consisting of:

(E)-9-(2,6-dimethylstyryl)-N-(4-(dimethylphosphoryl)phenyl)-2-(4-methyl-1H-imidazol-1-yl)-9H-purin-6-amine;

(E)-9-(2,6-dimethylstyryl)-N-(4-(dimethylphosphoryl)phenyl)-2-methoxy-9H-purin-6-amine;

(E)-9-(2,6-dimethylstyryl)-2-(2-(dimethylamino)ethoxy)-N-(4-(dipropylphosphoryl)phenyl)-9H-purin-6-amine;

(E)-9-(2,6-dimethylstyryl)-N-(4-(dimethylphosphoryl)phenyl)-2-(2-methoxyethoxy)-9H-purin-6-amine; and

(E)-9-(2,6-dimethylstyryl)-N-(4-(dimethylphosphoryl)phenyl)-2-(tetrahydro-2H-pyran-4-yloxy)-9H-purin-6-amine,

or a pharmaceutically acceptable salt thereof.

11. A compound according to claim 1 selected from the group consisting of:

(E)-9-(2,6-dimethylstyryl)-N-(4-(dimethylphosphoryl)phenyl)-2-(tetrahydrofuran-3-yloxy)-9H-purin-6-amine;

(E)-9-(2,6-dimethylstyryl)-2-(cyclopentyloxy)-N-(4-(dimethylphosphoryl)phenyl)-9H-purin-6-amine;

(E)-9-(2,6-dimethylstyryl)-N-(4-(dimethylphosphoryl)phenyl)-2-(1-methylpiperidin-4-yloxy)-9H-purin-6-amine;

(E)-9-(2,6-dimethylstyryl)-N-(4-(dimethylphosphoryl)phenyl)-2-(pyridin-3-yloxy)-9H-purin-6-amine; and

(E)-9-(2,6-dimethylstyryl)-N-(4-(dimethylphosphoryl)phenyl)-2-(methylthio)-9H-purin-6-amine,

or a pharmaceutically acceptable salt thereof.

12. A compound according to claim 1 selected from the group consisting of:

(E)-9-(2,6-dimethylstyryl)-N-(4-(dimethylphosphoryl)phenyl)-2-(methylsulfonyl)-9H-purin-6-amine;

(E)-9-(2,6-dimethylstyryl)-2-isopropyl-N-(4-(dimethylphosphoryl)phenyl)-9H-purin-6-amine;

(E)-9-(2,6-dimethylstyryl)-2-sec-butyl-N-(4-(dimethylphosphoryl)phenyl)-9H-purin-6-amine;

(E)-9-(2,6-dimethylstyryl)-2-cyclohexyl-N-(4-(dimethylphosphoryl)phenyl)-9H-purin-6-amine; and

(E)-9-(2,6-dimethylstyryl)-2-cyclopentyl-N-(4-(dimethylphosphoryl)phenyl)-9H-purin-6-amine,

or a pharmaceutically acceptable salt thereof.

13. A compound according to claim 1 selected from the group consisting of:

(E)-9-(2,6-dimethylstyryl)-N-(4-(dimethylphosphoryl)phenyl)-2-isobutyl-9H-purin-6-amine;

(E)-9-(2,6-dimethylstyryl)-N-(4-(dimethylphosphoryl)phenyl)-2-(pentan-3-yl)-9H-purin-6-amine;

(E)-3-(9-(2,6-dimethylstyryl)-6-(4-(dimethylphosphoryl)phenylamino)-9H-purin-2-yl)propanenitrile;

(E)-9-(2,6-dimethylstyryl)-2-(5-chlorothiophen-2-yl)-N-(4-(dimethylphosphoryl)phenyl)-9H-purin-6-amine; and

(E)-9-(2,6-dimethylstyryl)-N-(4-(dimethylphosphoryl)phenyl)-2-(thiophen-2-yl)-9H-purin-6-amine,

or a pharmaceutically acceptable salt thereof.

14. A compound according to claim 1 selected from the group consisting of:

(E)-9-(2,6-dimethylstyryl)-N-(4-(dimethylphosphoryl)phenyl)-2-(5-methylpyridin-2-yl)-9H-purin-6-amine;

(E)-9-(2,6-dimethylstyryl)-N-(4-(dimethylphosphoryl)phenyl)-2-(4-methylpyridin-2-yl)-9H-purin-6-amine;

(E)-N-(4-methyl-3-(2-(6-(2-N,N-dimethylaminoethylamino)-9H-purin-9-yl)vinyl)phenyl)-3-(trifluoromethyl)benzamide;

(E)-N-(4-methyl-3-(2-(6-(cyclopropylamino)-9H-purin-9-yl)vinyl)phenyl)-3-(trifluoromethyl)benzamide; and

(E)-3-(2-(6-(Phenylamino)-9H-purin-9-yl)vinyl)-4-methyl-N-(3-(4-methyl-1-imidazol-1-yl)-5-(trifluoromethyl)phenyl)benzamide,

or a pharmaceutically acceptable salt thereof.

15. A compound according to claim 1 selected from the group consisting of:

(E)-N-(4-Methyl-3-(2-(6-(pyridin-4-ylamino)-9H-purin-9-yl)vinyl)phenyl)-3-(trifluoromethyl)benzamide;

(E)-N-(4-Methyl-3-(2-(6-(pyridin-2-ylamino)-9H-purin-9-yl)vinyl)phenyl)-3-(trifluoromethyl)benzamide;

(E)-N-(4-methyl-3-(2-(6-(3-N,N-dimethylaminopropylamino)-9H-purin-9-yl)vinyl)phenyl)-3-(trifluoromethyl)benzamide;

(E)-3-(2-(6-(4-(Dimethylphosphoryl)phenylamino)-9H-purin-9-yl)vinyl)-4-methyl-N-(3-(trifluoromethyl)phenyl)benzamide; and

(E)-3-(2-(6-(4-(Dimethylphosphoryl)phenylamino)-9H-purin-9-yl)vinyl)-4-methyl-N-(5-tert-butylisoxazol-3-yl)benzamide,

or a pharmaceutically acceptable salt thereof.

16. A compound according to claim 1 selected from the group consisting of:

(E)-N-(4-Methyl-3-(2-(6-(pyrimidin-4-ylamino)-9H-purin-9-yl)vinyl)phenyl)-3-(trifluoromethyl)benzamide;

(E)-N-(4-methyl-3-(2-(6-(1-methylpiperidin-4-ylamino)-9H-purin-9-yl)vinyl)phenyl)-3-(trifluoromethyl)benzamide;

(E)-3-(2-(6-Cyclopropylamino)-9H-purin-9-yl)vinyl)-4-methyl-N-(5-tert-butylisoxazol-3-yl)benzamide;

(E)-3-(2-(6-Cyclopropylamino)-9H-purin-9-yl)vinyl)-4-methyl-N-(3-tert-butyl-1-methylpyrazol-5-yl)benzamide; and

(E)-3-(2-(6-Cyclopropylamino)-9H-purin-9-yl)vinyl)-4-methyl-N-(3-tert-butylpyrazol-5-yl)benzamide,

or a pharmaceutically acceptable salt thereof.

17. A compound according to claim 1 selected from the group consisting of:

(E)-3-(2-(6-Cyclopropylamino)-9H-purin-9-yl)vinyl)-4-methyl-N-(3-tert-butylphenyl)benzamide;

(E)-3-(2-(6-Cyclopropylamino)-9H-purin-9-yl)vinyl)-4-methyl-N-(4-chloro-3-trifluoromethylphenyl)benzamide;

(E)-3-(2-(6-Cyclopropylamino)-9H-purin-9-yl)vinyl)-4-methyl-N-(2-fluoro-5-trifluoromethylphenyl)benzamide;

(E)-3-(2-(6-Amino-9H-purin-9-yl)vinyl)-4-methyl-N-(4-(trifluoromethyl)pyridin-2-yl)benzamide; and

(E)-N-(3-(2-(6-(4-(Dimethylphosphoryl)phenylamino)-9H-purin-9-yl)vinyl)-4-methylphenyl)nicotinamide,

or a pharmaceutically acceptable salt thereof.

18. A compound according to claim 1 selected from the group consisting of:

(E)-N-(3-(2-(6-(4-(Dimethylphosphoryl)phenylamino)-9H-purin-9-yl)vinyl)-4-methylphenyl)-5-cyclopropylisoxazole-3-carboxamide;

(E)-N-(3-(2-(6-(4-cyanophenylamino)-9H-purin-9-yl)vinyl)-4-methylphenyl)-3-(trifluoromethyl)benzamide;

(E)-3-(2-(6-(Cyclopropylamino)-9H-purin-9-yl)vinyl)-4-methyl-N-(3-isopropylphenyl)benzamide; and

(E)-3-(2-(6-(Cyclopropylamino)-9H-purin-9-yl)vinyl)-4-methyl-N-(4-methylpyridin-2-yl)benzamide,

or a pharmaceutically acceptable salt thereof.

19. A pharmaceutical composition comprising a compound selected from the group consisting of:

(E)-N-(4-methyl-3-(2-(6-(methylamino)-9H-purin-9-yl)vinyl)phenyl)-3-(trifluoromethyl)benzamide;

N-(4-Methyl-3-(2-(6-(methylamino)-9H-purin-9-yl)ethyl)phenyl)-(trifluoromethyl)benzamide;

(E)-N-(3-(2-(6-(4-(Dimethylphosphoryl)phenylamino)-9H-purin-9-yl)vinyl)-4-methylphenyl)-3-(trifluoromethyl)benzamide;

(E)-3-(2-(6-(Cyclopropylamino)-9H-purin-9-yl)vinyl)-4-methyl-N-(3-(4-methyl-1-imidazol-1-yl)-5-(trifluoromethyl)phenyl)benzamide;

(E)-3-(2-(6-(Cyclopropylamino)-9H-purin-9-yl)vinyl)-4-methyl-N-(3-(trifluoromethyl)phenyl)benzamide;

(E)-1-(3-(2-(6-(Cyclopropylamino)-9H-purin-9-yl)vinyl)-4-methylphenyl)-3-(3-(trifluoromethyl)phenyl)urea;

(E)-3-(2-(6-(Cyclopropylamino)-9H-purin-9-yl)vinyl)-4-methyl-N-(4-(trifluoromethyl)pyridin-2-yl)benzamide;

(E)-3-(2-(6-Amino-9H-purin-9-yl)vinyl)-4-methyl-N-(3-(4-methyl-1H-imidazol-1-yl)-5-(trifluoromethyl)phenyl)benzamide;

(E)-N-(4-Methyl-3-(2-(6-(pyridin-3-ylamino)-9H-purin-9-yl)vinyl)phenyl)-3-(trifluoromethyl)benzamide;

(E)-9-(2-(2-Chloro-4-methylpyridin-3-yl)vinyl)-N-(4-(dimethylphosphoryl)phenyl)-9H-purin-6-amine;

(E)-9-(2,6-dimethylstyryl)-N-(4-(dimethylphosphoryl)phenyl)-9H-purin-6-amine;

(E)-9-(2-chloro-6-methylstyryl)-N-(4-(dimethylphosphoryl)phenyl)-9H-purin-6-amine;

(E)-9-(2-chloro-6-fluorostyryl)-N-(4-(dimethylphosphoryl)phenyl)-9H-purin-6-amine;

(E)-9-(2-methyl-6-ethylstyryl)-N-(4-(dimethylphosphoryl)phenyl)-9H-purin-6-amine;

(E)-9-(2-methyl-6-aminostyryl)-N-(4-(dimethylphosphoryl)phenyl)-9H-purin-6-amine;

(E)-9-(2-methyl-6-aminostyryl)-N-(4-(dimethylphosphoryl)phenyl)-9H-purin-6-amine;

(E)-9-(2-(1H-indol-4-yl)vinyl)-N-(4-(dimethylphosphoryl)phenyl)-9H-purin-6-amine;

(E)-4-(2-(6-(4-(dimethylphosphoryl)phenylamino)-9H-purin-9-yl)vinyl)indolin-2-one;

(E)-9-(2-(1H-indazol-4-yl)vinyl)-N-(4-(dimethylphosphoryl)phenyl)-9H-purin-6-amine;

(E)-N-(4-(dimethylphosphoryl)phenyl)-9-(2-(5-methyl-1H-indazol-4-yl)vinyl)-9H-purin-6-amine;

(E)-N-(4-(dimethylphosphoryl)phenyl)-9-(2-(5-methyl-1H-indol-4-yl)vinyl)-9H-purin-6-amine;

(E)-9-(2,6-dimethylstyryl)-N-(4-(dipropylphosphoryl)phenyl)-2-isopropyl-9H-purin-6-amine;

(E)-N-(4-(dipropylphosphoryl)phenyl)-2-isopropyl-9-styryl-9H-purin-6-amine;

N-(4-(Dipropylphosphoryl)phenyl)-2-isopropyl-9-(2-methylprop-1-enyl)-9H-purin-6-amine;

9-(Cyclohexylidenemethyl)-N-(4-(dipropylphosphoryl)phenyl)-2-isopropyl-9H-purin-6-amine;

(E)-9-(2-cyclopropylvinyl)-N-(4-(dipropylphosphoryl)phenyl)-2-isopropyl-9H-purin-6-amine;

(E)-9-(2,6-dimethylstyryl)-N-(4-(dimethylphosphoryl)phenyl)-2-morpholino-9H-purin-6-amine;

(E)-9-(2,6-dimethylstyryl)-N 6 -(4-(dimethylphosphoryl)phenyl)-9H-purine-2,6-diamine;

(E)-2-(4-(9-(2,6-dimethyl styryl)-6-(4-(dimethylphosphoryl)phenylamino)-9H-purin-2-yl)piperazin-1-yl)ethanol;

(E)-9-(2,6-dimethylstyryl)-N 6 -(4-(dimethylphosphoryl)phenyl)-N 2 ,N 2 -dimethyl-9H-purine-2,6-diamine;

(E)-9-(2,6-dimethylstyryl)-N-(4-(dimethylphosphoryl)phenyl)-2-(pyrrolidin-1-yl)-9H-purin-6-amine;

(E)-9-(2,6-dimethylstyryl)-N 2 -(2-(dimethylamino)ethyl)-N 6 -(4-(dimethylphosphoryl)phenyl)-9H-purine-2,6-diamine;

(E)-9-(2,6-dimethylstyryl)-N 2 -(2-(dimethylamino)ethyl)-N 6 -(4-(dimethylphosphoryl)phenyl)-N 2 -ethyl-9H-purine-2,6-diamine;

(E)-9-(2,6-dimethylstyryl)-N 6 -(4-(dimethylphosphoryl)phenyl)-N 2 -(2-methoxyethyl)-9H-purine-2,6-diamine;

(E)-9-(2,6-dimethylstyryl)-N 2 -(4-aminocyclohexyl)-N 6 -(4-(dimethylphosphoryl)phenyl)-9H-purine-2,6-diamine;

(E)-9-(2,6-dimethylstyryl)-N-(4-(dimethylphosphoryl)phenyl)-2-(piperazin-1-yl)-9H-purin-6-amine;

(E)-9-(2,6-dimethylstyryl)-N 2 -cyclopropyl-N 6 -(4-(dimethylphosphoryl)phenyl)-9H-purine-2,6-diamine;

(R,E)-2-(9-(2,6-dimethylstyryl)-6-(4-(dipropylphosphoryl)phenylamino)-9H-purin-2-ylamino)-3-methylbutan-1-ol;

(E)-9-(2,6-dimethylstyryl)-2-(4-(aminomethyl)piperidin-1-yl)-N-(4-(dipropylphosphoryl)phenyl)-9H-purin-6-amine;

(E)-9-(2,6-dimethylstyryl)-N-(4-(dimethylphosphoryl)phenyl)-2-(1H-imidazol-1-yl)-9H-purin-6-amine;

(E)-9-(2,6-dimethylstyryl)-N-(4-(dimethylphosphoryl)phenyl)-2-(4-methyl-1H-imidazol-1-yl)-9H-purin-6-amine;

(E)-9-(2,6-dimethylstyryl)-N-(4-(dimethylphosphoryl)phenyl)-2-methoxy-9H-purin-6-amine;

(E)-9-(2,6-dimethylstyryl)-2-(2-(dimethylamino)ethoxy)-N-(4-(dipropylphosphoryl)phenyl)-9H-purin-6-amine;

(E)-9-(2,6-dimethylstyryl)-N-(4-(dimethylphosphoryl)phenyl)-2-(2-methoxyethoxy)-9H-purin-6-amine;

(E)-9-(2,6-dimethylstyryl)-N-(4-(dimethylphosphoryl)phenyl)-2-(tetrahydro-2H-pyran-4-yloxy)-9H-purin-6-amine;

(E)-9-(2,6-dimethylstyryl)-N-(4-(dimethylphosphoryl)phenyl)-2-(tetrahydrofuran-3-yloxy)-9H-purin-6-amine;

(E)-9-(2,6-dimethylstyryl)-2-(cyclopentyloxy)-N-(4-(dimethylphosphoryl)phenyl)-9H-purin-6-amine;

(E)-9-(2,6-dimethylstyryl)-N-(4-(dimethylphosphoryl)phenyl)-2-(1-methylpiperidin-4-yloxy)-9H-purin-6-amine;

(E)-9-(2,6-dimethylstyryl)-N-(4-(dimethylphosphoryl)phenyl)-2-(pyridin-3-yloxy)-9H-purin-6-amine;

(E)-9-(2,6-dimethylstyryl)-N-(4-(dimethylphosphoryl)phenyl)-2-(methylthio)-9H-purin-6-amine;

(E)-9-(2,6-dimethylstyryl)-N-(4-(dimethylphosphoryl)phenyl)-2-(methylsulfonyl)-9H-purin-6-amine;

(E)-9-(2,6-dimethylstyryl)-2-isopropyl-N-(4-(dimethylphosphoryl)phenyl)-9H-purin-6-amine;

(E)-9-(2,6-dimethylstyryl)-2-sec-butyl-N-(4-(dimethylphosphoryl)phenyl)-9H-purin-6-amine;

(E)-9-(2,6-dimethylstyryl)-2-cyclohexyl-N-(4-(dimethylphosphoryl)phenyl)-9H-purin-6-amine;

(E)-9-(2,6-dimethylstyryl)-2-cyclopentyl-N-(4-(dimethylphosphoryl)phenyl)-9H-purin-6-amine;

(E)-9-(2,6-dimethylstyryl)-N-(4-(dimethylphosphoryl)phenyl)-2-isobutyl-9H-purin-6-amine;

(E)-9-(2,6-dimethylstyryl)-N-(4-(dimethylphosphoryl)phenyl)-2-(pentan-3-yl)-9H-purin-6-amine;

(E)-3-(9-(2,6-dimethylstyryl)-6-(4-(dimethylphosphoryl)phenylamino)-9H-purin-2-yl)propanenitrile;

(E)-9-(2,6-dimethylstyryl)-2-(5-chlorothiophen-2-yl)-N-(4-(dimethylphosphoryl)phenyl)-9H-purin-6-amine;

(E)-9-(2,6-dimethylstyryl)-N-(4-(dimethylphosphoryl)phenyl)-2-(thiophen-2-yl)-9H-purin-6-amine;

(E)-9-(2,6-dimethylstyryl)-N-(4-(dimethylphosphoryl)phenyl)-2-(5-methylpyridin-2-yl)-9H-purin-6-amine;

(E)-9-(2,6-dimethylstyryl)-N-(4-(dimethylphosphoryl)phenyl)-2-(4-methylpyridin-2-yl)-9H-purin-6-amine;

(E)-N-(4-methyl-3-(2-(6-(2-N,N-dimethylaminoethylamino)-9H-purin-9-yl)vinyl)phenyl)-3-(trifluoromethyl)benzamide;

(E)-N-(4-methyl-3-(2-(6-(cyclopropylamino)-9H-purin-9-yl)vinyl)phenyl)-3-(trifluoromethyl)benzamide;

(E)-3-(2-(6-(Phenylamino)-9H-purin-9-yl)vinyl)-4-methyl-N-(3-(4-methyl-1-imidazol-1-yl)-5-(trifluoromethyl)phenyl)benzamide;

(E)-N-(4-Methyl-3-(2-(6-(pyridin-4-ylamino)-9H-purin-9-yl)vinyl)phenyl)-3-(trifluoromethyl)benzamide;

(E)-N-(4-Methyl-3-(2-(6-(pyridin-2-ylamino)-9H-purin-9-yl)vinyl)phenyl)-3-(trifluoromethyl)benzamide;

(E)-N-(4-methyl-3-(2-(6-(3-N,N-dimethylaminopropylamino)-9H-purin-9-yl)vinyl)phenyl)-3-(trifluoromethyl)benzamide;

(E)-3-(2-(6-(4-(Dimethylphosphoryl)phenylamino)-9H-purin-9-yl)vinyl)-4-methyl-N-(3-(trifluoromethyl)phenyl)benzamide;

(E)-3-(2-(6-(4-(Dimethylphosphoryl)phenylamino)-9H-purin-9-yl)vinyl)-4-methyl-N-(5-tert-butylisoxazol-3-yl)benzamide;

(E)-N-(4-Methyl-3-(2-(6-(pyrimidin-4-ylamino)-9H-purin-9-yl)vinyl)phenyl)-3-(trifluoromethyl)benzamide;

(E)-N-(4-methyl-3-(2-(6-(1-methylpiperidin-4-ylamino)-9H-purin-9-yl)vinyl)phenyl)-3-(trifluoromethyl)benzamide;

(E)-3-(2-(6-Cyclopropylamino)-9H-purin-9-yl)vinyl)-4-methyl-N-(5-tert-butylisoxazol-3-yl)benzamide;

(E)-3-(2-(6-Cyclopropylamino)-9H-purin-9-yl)vinyl)-4-methyl-N-(3-tert-butyl-1-methylpyrazol-5-yl)benzamide;

(E)-3-(2-(6-Cyclopropylamino)-9H-purin-9-yl)vinyl)-4-methyl-N-(3-tert-butylpyrazol-5-yl)benzamide;

(E)-3-(2-(6-Cyclopropylamino)-9H-purin-9-yl)vinyl)-4-methyl-N-(3-tert-butylphenyl)benzamide;

(E)-3-(2-(6-Cyclopropylamino)-9H-purin-9-yl)vinyl)-4-methyl-N-(4-chloro-3-trifluoromethylphenyl)benzamide;

(E)-3-(2-(6-Cyclopropylamino)-9H-purin-9-yl)vinyl)-4-methyl-N-(2-fluoro-5-trifluoromethylphenyl)benzamide;

(E)-3-(2-(6-Amino-9H-purin-9-yl)vinyl)-4-methyl-N-(4-(trifluoromethyl)pyridin-2-yl)benzamide;

(E)-N-(3-(2-(6-(4-(Dimethylphosphoryl)phenylamino)-9H-purin-9-yl)vinyl)-4-methylphenyl)nicotinamide;

(E)-N-(3-(2-(6-(4-(Dimethylphosphoryl)phenylamino)-9H-purin-9-yl)vinyl)-4-methylphenyl)-5-cyclopropylisoxazole-3-carboxamide;

(E)-N-(3-(2-(6-(4-cyanophenylamino)-9H-purin-9-yl)vinyl)-4-methylphenyl)-3-(trifluoromethyl)benzamide;

(E)-3-(2-(6-(Cyclopropylamino)-9H-purin-9-yl)vinyl)-4-methyl-N-(3-isopropylphenyl)benzamide; and

(E)-3-(2-(6-(Cyclopropylamino)-9H-purin-9-yl)vinyl)-4-methyl-N-(4-methylpyridin-2-yl)benzamide,

or a pharmaceutically acceptable salt thereof; and

a pharmaceutically acceptable carrier or adjuvant.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jun 23, 2021
From: ARIAD PHARMACEUTICALS, INC.
To: TAKEDA PHARMACEUTICAL COMPANY LIMITED
Reel/Frame 056637/0879 →
Continuity (3)
Continuation 11990299
Provisional Application 60707423 · Aug 11, 2005
Related Publication 20120178716A1 · Jul 12, 2012