Pyrrolopyrimidine compounds and their uses
View Patent ↗The present application describes organic compounds that are useful for the treatment, prevention and/or amelioration of diseases, particularly pyrrolopyrimidine compounds and derivatives are described which inhibit protein kinases. The organic compounds are useful in treating proliferative disease.
1. A compound of Formula I:
or a pharmaceutically acceptable salt thereof, wherein:
the dashed line indicates a double bond;
A is N;
R 2 is hydrogen and R 3 is selected from the group consisting of hydrogen, hydroxyl, C 1 -C 3 -alkyl, C 3 -C 8 -cycloalkyl, heterocyclyl, aryl, heteroaryl, substituted C 1 -C 3 -alkyl, substituted C 3 -C 8 -cycloalkyl, substituted heterocyclyl, substituted aryl and substituted heteroaryl;
R 4 is selected from the group consisting of hydrogen, branched C 1 -C 5 -alkyl, branched C 1 -C 5 -alkyl substituted by phenyl and C 3 -C 6 -cycloalkyl;
X is CR 11 and Y is CR 12 ;
R 11 is hydrogen or C 1 -C 3 -alkyl and
R 12 is BC(O)NR 13 R 14 ; wherein B is a bond, C 1 -C 3 -alkyl or branched C 1 -C 3 -alkyl; wherein R 13 and R 14 are each, independently, selected from the group consisting of hydrogen, C 1 -C 3 -alkyl, C 3 -C 8 -cycloalkyl, heterocyclyl, aryl, heteroaryl, substituted alkyl, substituted cycloalkyl, substituted heterocyclyl, substituted aryl, and substituted heteroaryl.
2. The compound of claim 1 , wherein R 4 is C(H)(CH 2 CH 3 ) 2 , C(H)(CH 2 CH 3 )Ph, CH 2 CH 3 , cyclopropyl, cyclopentyl or cyclohexyl.
3. The compound of claim 1 , wherein R 3 is an aryl group, which is further independently substituted one or more times by halogen, C 1 -C 4 -alkoxy, R 15 -amine, R 15 -heterocycle, or R 15 -heteroaryl, wherein R 15 is a bond, C(O), N(H)C(O), N(H)SO 2 , OC(O) or (CH 2 ) 1-4 , wherein the (CH 2 ) 1-4 group may be interrupted by O, N(CH 3 ) or N(H).
4. The compound of claim 3 , wherein the aryl group is phenyl.
5. The compound of claim 1 , wherein the phenyl group is R 3 is phenyl which is further independently substituted one or more times with fluoro, methoxy, diethylamine, R 15 -piperazinyl, R 15 -morpholinyl, R 15 -piperidinyl, R 15 -triazolyl, R 15 -phenyl, R 15 -pyridinyl, R 15 -piperazinyl, R 15 -indazolyl, R 15 -pyrrolidinyl or R 15 -imidazolyl, wherein the piperazinyl, morpholinyl, piperidinyl, triazolyl, phenyl, pyridinyl, piperazinyl, indazolyl, pyrrolidinyl or imidazolyl groups may be further substituted with C 1 -C 4 -alkyl, C(O)C 1 -C 4 -alkyl, S(O) 2 C 1 -C 4 -alkyl, OH, C(O)(CH 2 ) 1-3 CN or N(H)C(O)C 1 -C 4 -alkyl and wherein R 15 is a bond, C(O), N(H)C(O), N(H)SO 2 , OC(O) or (CH 2 ) 1-4 , wherein the (CH 2 ) 1-4 group may be interrupted by O, N(CH 3 ) or N(H).
6. The compound of claim 1 , wherein R 3 is phenyl which is further substituted by N(H)C(O)aryl, C(O)N(H)C 1 -C 4 -alkyl, C(O)N(C 1 -C 4 -alkyl) 2 or C(O)N(H)C 3 -C 6 -cycloalkyl.
7. The compound of claim 1 , wherein the compound is selected from the group consisting of
8. A compound of Formula I:
or a pharmaceutically acceptable salt thereof, wherein:
the dashed line indicates a double bond;
A is N;
R 2 is hydrogen and R 3 is selected from the group consisting of hydrogen, hydroxyl, C 1 -C 3 -alkyl, C 3 -C 8 -cycloalkyl, heterocyclyl, aryl, heteroaryl, substituted C 1 -C 3 -alkyl, substituted C 3 -C 8 -cycloalkyl, substituted heterocyclyl, substituted aryl and substituted heteroaryl;
R 4 is branched or linear C 1 -C 5 -alkyl, wherein the branched C 1 -C 5 -alkyl group may be interrupted by one or more heteroatoms, and/or substituted with one or more heteroatoms, halogens, C 3 -C 8 cycloalkyl groups, substituted C 3 -C 8 cycloalkyl groups, C 3 -C 8 hetrocyclyl groups, aryl groups, heteroaryl groups, substituted aryl groups, or substituted heteroaryl groups;
X is CR 11 and Y is CR 12 ;
R 11 is hydrogen or C 1 -C 3 -alkyl and
R 12 is BC(O)NR 13 R 14 ; wherein B is a bond, C 1 -C 3 -alkyl or branched C 1 -C 3 -alkyl; wherein R 13 and R 14 are each, independently, selected from the group consisting of hydrogen, C 1 -C 3 -alkyl, C 3 -C 8 -cycloalkyl, heterocyclyl, aryl, heteroaryl, substituted alkyl, substituted cycloalkyl, substituted heterocyclyl, substituted aryl, and substituted heteroaryl.
9. A pharmaceutical composition comprising a compound according to claim 1 or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier or excipient.