Fused tricyclic ring derivatives as Src homology-2 phosphate inhibitors
The present disclosure provides certain fused tricyclic ring derivatives that are Src Homology-2 phosphatase (SHP2) inhibitors and are therefore useful for the treatment of diseases treatable by inhibition of SHP2. Also provided are pharmaceutical compositions containing such compounds and processes for preparing such compounds.
1. A compound of Formula (A):
wherein X is halogen or thiol;
Y is null, CH 2 , O, or C═O;
Z is CH 2 or O; and
R is selected from null, hydrogen, alkyl, alkoxy, hydroxyl, methoxyalkoxy, heterocyclylmethyloxy, and cycloalkylmethoxymethyl.
2. The compound of claim 1 , wherein X is halogen.
3. The compound of claim 1 , wherein X is iodine or bromine.
4. The compound of claim 1 , where X is thiol.
5. The compound of claim 1 , wherein Y is O.
6. The compound of claim 1 , wherein Y is CH 2 .
7. The compound of claim 1 , where Z is O.
8. The compound of claim 1 , where Z is CH 2 .
9. The compound of claim 1 , that is ((6aS,8S)-4-iodo-6a,7, tetrahydro-6H-pyrido[3,2-b]pyrrolo[1,2-d][1,4]oxazin-8-yl)methanol:
10. The compound of claim 1 , that is (6aS,8S)-4-iodo-6a,7,8,9-tetrahydro-6H-pyrido[3,2-b]pyrrolo[1,2-d][1,4]oxazin-8-ol: