Heteroaryl compounds and uses thereof
The present invention provides compounds, pharmaceutically acceptable compositions thereof, and methods of using the same.
1. A method for inhibiting at least one mutant of epidermal growth factor receptor (“EGFR”) selectively as compared to wild-type epidermal growth factor receptor (“WT EGFR”), in a biological sample or in a patient, comprising contacting the biological sample with, or administering to the patient, a compound of formula I:
or a pharmaceutically acceptable salt thereof, wherein:
W is —O— or —NH—;
R 1 is —OR;
each R is independently C 1-4 alkyl or C 1-4 fluoroalkyl;
each of R 2 and R 3 is independently hydrogen, —OH, or —OR; and
R 4 is —CF 3 , Cl, or Br; and
wherein the compound is not
2. The method according to claim 1 , wherein said compound is sparing for WT EGFR.
3. The method according to claim 1 , wherein the at least one mutant of EGFR is T790M.
4. The method according to claim 2 , wherein the at least one mutant of EGFR is T790M.
5. The method according to claim 1 , wherein the at least one mutant of EGFR is an activating mutant.
6. The method according to claim 5 , wherein the activating mutant is selected from a deletion mutant and a point mutation.
7. The method according to claim 6 , wherein the deletion mutant is delE746-A750.
8. The method according to claim 6 , wherein the point mutation is selected from L858R and G719S.
9. The method according to claim 1 , wherein the compound selectively inhibits at least one activating mutant and T790M.
10. The method according to claim 9 wherein the activating mutant is selected from a deletion mutant and a point mutation.
11. The method according to claim 10 , wherein the deletion mutant is delE746-A750.
12. The method according to claim 10 , wherein the point mutation is selected from L858R and G719S.
13. A method for modulating a mutant epidermal growth factor receptor (“EGFR”) in a patient, comprising administering to the patient a compound of formula I:
or a pharmaceutically acceptable salt thereof, wherein:
W is —O— or —NH—;
R 1 is —OR;
each R is independently C 1-4 alkyl or C 1-4 fluoroalkyl;
each of R 2 and R 3 is independently hydrogen, —OH, or —OR; and
R 4 is —CF 3 , Cl, or Br, wherein the compound is not
14. The method according to claim 13 , wherein the patient is suffering from a cancer.
15. The method according to claim 14 , wherein the cancer is non-small cell lung cancer.
16. The method according to claim 1 , wherein the compound has at least one definition selected from (a), (b), (c), (d), or (e):
(a) W is —O—,
(b) R 1 is —OCH 3 ;
(c) R 2 is hydrogen or —OCH 3 ;
(d) R 3 is hydrogen or —OCH 3 ; or
(e) R 4 is —CF 3 or —Cl.
17. The method according to claim 16 , wherein the compound has at least two, at least three, or at least four definitions selected from (a), (b), (c), (d), or (e).
18. The method according to claim 1 , wherein the compound has at least one definition selected from (a), (b), (c), (d), or (e):
(a) W is —NH—;
(b) R 1 is —OCH 3 ;
(c) R 2 is hydrogen or —OCH 3 ;
(d) R 3 is hydrogen or —OCH 3 ; or
(e) R 4 is —CF 3 or —Cl.
19. The method according to claim 18 , wherein the compound has at least two, at least three, or at least four definitions selected from (a), (b), (c), (d), or (e).
20. The method according to claim 1 , wherein the compound is selected from:
or a pharmaceutically acceptable salt thereof.