HETEROCYCLIC COMPOUNDS AND USES THEREOF
The present invention provides compounds, pharmaceutically acceptable compositions thereof, and methods of using the same.
1 - 36 . (canceled)
37 . A method for selectively inhibiting at least one mutant of EGFR as compared to 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-a
or a pharmaceutically acceptable salt thereof, wherein:
n is 0, 1, or 2;
m is 0, 1, or 2, wherein m and n are not simultaneously 0;
W is —NH—;
R 1 is —OR;
each R is independently C 1-4 alkyl or C 1-4 fluoroalkyl;
R 2 is —CF 3 , Cl, or Br; and
G is —O—.
38 . The method according to claim 37 , wherein said method is sparing for WT EGFR.
39 . The method according to claim 37 , wherein the at least one mutant is T790M.
40 . The method according to claim 38 , wherein the at least one mutant is T790M.
41 . The method according to claim 37 , wherein the at least one mutant of EGFR is an activating mutant.
42 . The method according to claim 39 , wherein the at least one activating mutant of EGFR is a deletion mutant.
43 . The method according to claim 41 , wherein the at least one activating mutant of EGFR is a point mutation.
44 . The method according to claim 42 , wherein the at least one activating mutant is delE746-A750.
45 . The method according to claim 43 , wherein the at least one activating mutant is L858R.
46 . The method according to claim 43 , wherein the at least one activating mutant is G719S.
47 . The method according to claim 37 , wherein the compound selectively inhibits at least one activating mutant and T790M.
48 . The method according to claim 47 , wherein the at least one activating mutant of EGFR is a deletion mutant.
49 . The method according to claim 47 , wherein the at least one mutant of EGFR is a point mutation.
50 . The method according to claim 48 , wherein the at least one activating mutant is delE746-A750.
51 . The method according to claim 49 , wherein the at least one activating mutant is L858R.
52 . The method according to claim 49 , wherein the at least one activating mutant is G719S.
53 . (canceled)
54 . A method for treating a mutant EGFR-mediated disorder or condition in a patient, comprising administering to the patient a compound of formula I-a:
or a pharmaceutically acceptable salt thereof, wherein:
n is 0, 1, or 2;
m is 0, 1, or 2, wherein m and n are not simultaneously 0;
W is —NH—;
R 1 is —OR;
each R is independently C 1-4 alkyl or C 1-4 fluoroalkyl;
R 2 is —CF 3 , Cl, or Br; and
G is —O—.
55 . The method according to claim 54 , wherein the disorder or condition is a cancer.
56 . The method according to claim 55 , wherein the cancer is non-small cell lung cancer.
57 - 62 . (canceled)
63 . The method according to claim 37 , wherein the compound is of formula II:
or a pharmaceutically acceptable salt thereof.
64 . The compound according to claim 63 , wherein R 2 is —CF 3 .
65 . The compound according to claim 63 , wherein R 2 is Cl.
66 . The compound according to claim 63 , wherein the compound is selected from: selected from:
or a pharmaceutically acceptable salt thereof.