Inhibitors of the fibroblast growth factor receptor
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 1, or 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, or 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 the group consisting of
wherein X is halo or triflate; and
each of R a , R b , and R c is independently, H, substituted or unsubstituted C 1-4 alkyl, substituted or unsubstituted C 1-4 cycloalkyl, or cyano.
2. The compound of claim 1 , wherein X is N and Y is CH.
3. The compound of claim 2 , wherein A is phenyl.
4. The compound of claim 1 , wherein two R 2 are chloro and two R 2 are methoxy.
5. The compound of claim 4 , wherein R 1 is methyl.
6. The compound of claim 5 , wherein q is 0.
7. The compound of claim 1 , wherein Warhead is
8. A compound selected from the group consisting of:
or a pharmaceutically acceptable salt thereof.
9. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a compound of claim 1 .