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 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 .