Inhibitors of the fibroblast growth factor receptor

Patent metadata

Field	Value
Publication number	US-9340514-B2
Application number	US-201514677162-A
Country	US
Kind code	B2
Filing date	Apr 2, 2015
Priority date	Jul 11, 2012
Publication date	May 17, 2016
Grant date	May 17, 2016

Abstract

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.

First claim

We claim:

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.

Assignees

• Blueprint Medicines Corp

Inventors

• Bifulco Jr Neil
• Brooijmans Natasja
• Hodous Brian L
• Kim Joseph L
• Miduturu Chandrasekhar V

Classifications

• A61P35/00

  Antineoplastic agents · CPC title

• A61P3/06

  Antihyperlipidemics · CPC title

• A61P25/00

  Drugs for disorders of the nervous system · CPC title

• A61P1/16

  for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics · CPC title

• A61K31/4375 Primary

  the heterocyclic ring system containing a six-membered ring having nitrogen as a ring heteroatom, e.g. quinolizines, naphthyridines, berberine, vincamine · CPC title