Tricyclic heterocyclic compounds as phosphoinositide 3-kinase inhibitors

1. A compound of formula I:

or a pharmaceutically acceptable salt thereof, wherein:

W is selected from the group consisting of O, N—H, N—(C 1 -C 10 alkyl) and 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 0;

R 2 is LY;

each L is selected from the group consisting of a direct bond, C 1 -C 10 alkylene, C 2 -C 10 alkenylene and C 2 -C 10 alkynylene;

Y is an optionally substituted fused, bridged or spirocyclic non-aromatic 5-12 membered heterocycle containing up to 4 heteroatoms selected from N or O; and

each R 3 is independently selected from the group consisting of H, C 1 -C 10 alkyl, halogen, fluoro C 1 -C 10 alkyl, O—C 1 -C 10 alkyl, NH—C 1 -C 10 alkyl, S—C 1 -C 10 alkyl, O-fluoro C 1 -C 10 alkyl, NH-acyl, NH—C(O)—NH—C 1 -C 10 alkyl, C(O)—NH—C 1 -C 10 alkyl, aryl and heteroaryl.

2. The compound according to claim 1 , wherein R 1 is morpholine.

3. The compound according to claim 1 , wherein W is O.

4. The compound according to claim 1 , wherein X is CH.

5. The compound according to claim 1 , wherein R 3 is H.

6. The compound according to claim 1 , wherein L is C 1 -C 10 alkylene.

7. The compound according to claim 1 , wherein Y is selected from:

wherein:

A is selected from the group consisting of O, S, NR 4 , C 1 -C 3 alkylene, C 2 -C 3 alkenylene and C 2 -C 3 alkynylene, wherein C 1 -C 3 alkylene, C 2 -C 3 alkenylene and C 2 -C 3 alkynylene are optionally substituted;

W is selected from the group consisting of NR 4 , O and CH 2 ;

wherein R 4 is selected from the group consisting of H, C 1 -C 10 alkyl, C 2 -C 10 alkenyl and C 2 -C 10 alkynyl, wherein C 1 -C 10 alkyl, C 2 -C 10 alkenyl and C 2 -C 10 alkynyl are optionally substituted;

p is 1

each m is independently selected from the group consisting of 0, 1 and 2; and

each n is independently selected from the group consisting of 1, 2, and 3.

8. The compound according to claim 7 , wherein A is O or C 1 -C 3 alkylene.

9. The compound according to claim 7 , wherein W is O or CH 2 .

10. The compound according to claim 1 , wherein the compound is a compound selected from the group consisting of:

or a pharmaceutically acceptable salt of any of the foregoing.

11. A pharmaceutical composition comprising the compound according to claim 1 , and a pharmaceutically acceptable excipient.

12. A compound represented by:

or a pharmaceutically acceptable salt thereof, wherein:

R 33 is independently selected for each occurrence from the group consisting of H, halogen, NH—C 1-3 alkyl, NH 2 , C 1-6 alkyl and O—C 1-6 alkyl, wherein C 1-6 alkyl for each occurrence is optionally substituted by one, two or three substituents selected from halogen or hydroxyl;

R 34 is selected from H or C 1-3 alkyl; and

R 44 and R 45 , when taken together with the nitrogen to which they are attached form a 7-10 membered bicyclic spirocycle or bridged heterocycle each having an additional heteroatom selected from the group consisting of O, S, and NR 55 , wherein R 55 is H or C 1-3 alkyl.

13. The compound of claim 12 , wherein R 44 and R 45 , when taken together with the nitrogen to which they are attached form a 7-8 membered bicyclic bridged heterocycle represented by:

wherein:

D is selected from the group consisting of O, S and NR 55 ;

E is (CH 2 ) r , wherein r is 1 or 2,

V is O or NR 55 , and

R 55 is H or C 1-3 alkyl.

14. The compound of claim 12 , wherein R 44 and R 45 , when taken together with the nitrogen to which they are attached form a 7-10 membered spirocycle having one additional heteroatom selected from O or NR 55 , wherein R 55 is H or C 1-3 alkyl.