Tricyclic heterocyclic compounds as phosphoinositide 3-kinase inhibitors
Compounds of formula (I) or a pharmaceutically acceptable salt thereof, wherein: W is O, N—H, N-(C 1 -C 10 alkyl) or S; each X is independently CH or N; R 1 is a 5 to 7-membered saturated or unsaturated, optionally substituted heterocycle containing at least 1 heteroatom selected from N or O; R 2 is (LQ) m Y; and each R 3 is independently H, C 1 -C 10 alkyl, aryl or heteroaryl, are surprisingly found to be inhibitors of PI3K-p110δ, and therefore have utility in therapy.
1. A compound represented by formula I:
or a pharmaceutically acceptable salt thereof, wherein:
W is O;
Xis CH;
R 2 is (LQ) m Y;
m is 1;
L is: C 1 alkylene;
Q is selected from the group consisting of: heteroarylene, —NR 3 —, —C(O)—, —NR 4 R 5 —, and —C(O)NR 4 R 5 , where R 4 and R 5 together with the nitrogen to which they are attached form a 5 to 7-membered heterocycle linker;
Y is selected from the group consisting of: H, C 1 -C 10 alkyl, C 3 -C 10 cycloalkyl, —OR 3 , —N(R 3 ) 2 , —SO 2 —R 3 , —SO 2 —N(R 3 ) 2 , halogen, —CN, and —C(halogen) b R 3 ( 3−b ),
b is from 1 to 3; and
R 3 is independently selected for each occurrence from H or C 1 -C 10 alkyl.
2. The compound according to claim 1 , wherein both of the R 3 groups that are attached to the 6,5-ring system in formula I are H.
3. The compound according to claim 1 , wherein Q is —NR 4 R 5 wherein R 4 and R 5 together with the nitrogen to which they are attached form a 5 to 7-membered heterocycle linker having an additional heteroatom O; and Y is H.
4. A compound selected from the structures shown below:
or a pharmaceutically acceptable salt thereof.
5. A pharmaceutical composition comprising a compound according to claim 1 , and a pharmaceutically acceptable excipient.
6. The compound according to claim 1 , wherein Q is selected from —NR 3 —and —NR 4 R 5 —.