Inhibitors of the fibroblast growth factor receptor
View Patent ↗Described herein are inhibitors of FGFR, pharmaceutical compositions including such compounds, and methods of using such compounds and compositions to inhibit the activity of tyrosine kinases.
1. A compound of Formula I, or a pharmaceutically acceptable salt thereof:
wherein:
Ring A is a 3-8 membered aryl, heteroaryl, heterocyclic or alicyclic group;
X is CH or N;
Y is CH or N—R 4 where R 4 is H or C 1-6 alkyl;
L is —[C(R 5 )(R 6 )] q —, where each of R 5 and R 6 is, independently, H or C 1-6 alkyl; wherein q is 0-4;
each of R 1 and R 3 is, independently, halo, cyano, optionally substituted C 1-6 alkoxy, hydroxy, oxo, amino, amido, alkyl urea, optionally substituted C 1-6 alkyl, optionally substituted C 1-6 heterocyclyl;
two R 2 are halo and two R 2 are C 1-6 alkoxy;
m is 0-3;
n is 4;
p is 0-2; and
Warhead is selected from:
wherein X is a leaving group selected from halo and triflate; and each of R a , R b , and R c is, independently, H; substituted or unsubstituted C 1-4 alkyl; or substituted or unsubstituted C 1-4 cycloalkyl.
2. The compound of claim 1 , wherein Warhead is
3. The compound of claim 1 , wherein A is aryl.
4. The compound of claim 3 , wherein A is phenyl.
5. The compound of claim 1 , wherein A is heteroaryl.
6. The compound of claim 5 , wherein A is selected from pyrrole, furan, thiophene, imidazole, oxazole, thiazole, triazole, pyrazole, pyridine, pyrazine, pyridazine and pyrimidine.
7. The compound of claim 1 , wherein A is heterocyclic.
8. The compound of claim 7 , wherein A is selected from pyrrolidine, piperidine, piperazine, and morpholine.
9. The compound of claim 1 , wherein A is alicyclic.
10. The compound of claim 1 , wherein X is N and Y is N—R 4 .
11. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a compound of Formula I, or a pharmaceutically acceptable salt thereof.