Quinazoline based EGFR inhibitors
The present invention relates to quinazoline containing zinc-binding moiety based derivatives of formula I that have enhanced and unexpected properties as inhibitors of epidermal growth factor receptor tyrosine kinase (EGFR-TK) and their use in the treatment of EGFR-TK related diseases and disorders such as cancer.
1. A compound represented by formula (IV):
or a pharmaceutically acceptable salt or ester thereof, wherein
B is an unsubstituted or hydroxy substituted C 3 to C 9 alkylene; and
R 1 is selected from hydrogen, hydroxy, C 1 to C 4 alkoxy or substituted C 1 to C 4 alkoxy.
2. The compound of claim 1 or a pharmaceutically acceptable salt or ester thereof wherein B is an unsubstituted or hydroxy substituted straight chain C 5 to C 7 alkylene.
3. The compound of claim 2 or a pharmaceutically acceptable salt or ester thereof wherein R 1 is hydroxy or methoxy and B is an unsubstituted or hydroxy substituted-straight chain C 6 alkylene.
4. A pharmaceutical composition comprising as an active ingredient a compound of claim 1 or a pharmaceutically acceptable salt or ester thereof and a pharmaceutical acceptable carrier.
5. A compound represented by formula (V):
or a pharmaceutically acceptable salt or ester thereof, wherein
B is an unsubstituted or hydroxy substituted C 3 to C 9 alkylene; and
R 1 is selected from hydrogen, hydroxy, C 1 to C 4 alkoxy or substituted C 1 to C 4 alkoxy.
6. The compound of claim 5 or a pharmaceutically acceptable salt or ester thereof wherein B is an unsubstituted or hydroxy substituted straight chain C 5 to C 7 alkylene.
7. The compound of claim 6 or a pharmaceutically acceptable salt or ester thereof wherein R 1 is hydroxy or methoxy and B is an unsubstituted or hydroxy substituted straight chain C 6 alkylene.
8. A pharmaceutical composition comprising as an active ingredient a compound of claim 5 or a pharmaceutically acceptable salt or ester thereof and a pharmaceutical acceptable carrier.
9. A compound of the formula:
or a pharmaceutically acceptable salt or ester thereof.
10. A pharmaceutical composition comprising as an active ingredient a compound of claim 9 or a pharmaceutically acceptable salt or ester thereof and a pharmaceutical acceptable carrier.