Methods of inhibiting Ire1
Disclosed herein are, inter alia, methods for inhibiting Ire1 activity.
1. A method of decreasing Ire1 activity by contacting Ire1 with an effective amount of a compound having the formula:
wherein Z 1 and Z 2 are independently N;
R 1 and R 2 are independently hydrogen, substituted or unsubstituted alkyl, or substituted or unsubstituted heteroalkyl;
ring A is arylenyl;
ring B is aryl;
R 3 is independently halogen, —CN, —CF 3 , —SH, —N(O), —N(O) 2 , —NH 2 , —C(O)H, —C(O)OH, —N═NH, —NH—C(O)H, —NH—C(O)—OH, —C(O)NH 2 , —NHS 2 H, —S(O) 2 NH 2 , —OH, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;
R 5 is independently halogen, —CN, —CF 3 , —SH, —N(O), —N(O) 2 , —NH 2 , —C(O)H, —C(O)OH, —N═NH, —NH—C(O)H, —NH—C (O)—OH, —C(O)NH 2 , —NHSO 2 H, —SO 2 NH 2 , —OH, or unsubstituted C 1 -C 4 alkyl or substituted or unsubstituted 2 to 4 membered heteroalkyl;
x is 0;
y is an integer from 0 to 5;
L 1 is a bond, substituted or unsubstituted alkylene, or substituted or unsubstituted heteroalkylene;
L 2 is —C(O)—;
L 3 is a bond or —N(H)—; and
L 4 is —NH—.
2. The method of claim 1 , wherein R 1 and R 2 are independently hydrogen or C 1-10 unsubstituted alkyl.
3. The method claim 1 , wherein ring A is unsubstituted phenylenyl.
4. The method of claim 1 , wherein ring B is phenyl.
5. The method of claim 1 , wherein R 3 is substituted or unsubstituted C 1-10 alkyl, substituted or unsubstituted C 3-8 cycloalkyl, or substituted or unsubstituted 5-6 membered heterocycloalkyl.
6. The method of claim 1 , wherein R 5 is —CF 3 , F, Br, Cl, I, NO 2 , CH 3 , C 2 H 5 , SH, OH, OMe, CN, SMe, NO, or C(O)H.
7. The method of claim 1 , wherein y is 0 or 1.
8. The method of claim 1 , wherein L 1 is a bond or substituted or unsubstituted alkylene.
9. The method of claim 1 , wherein L 3 is a bond.
10. The method of claim 1 , wherein L 3 is —N(H)—.
11. The method claim 1 , wherein the compound is one of the formulae:
12. The method of claim 1 , wherein the method comprises decreasing hIre1 activity.
13. The method claim 1 , wherein R 1 and R 2 are hydrogen.
14. The method claim 1 , wherein L 1 is a substituted or unsubstituted methylene.
15. The method claim 1 , wherein L 1 is unsubstituted methylene.
16. The method of claim 1 , wherein R 3 is unsubstituted C 1-4 alkyl, unsubstituted C 3-6 cycloalkyl, or unsubstituted 5-membered heterocycloalkyl.