Substituted benzofuranyl and benzoxazolyl compounds and uses thereof
View Patent ↗The invention generally relates to substituted benzofuranyl and substituted benzoxazolyl compounds, and more particularly to a compound represented by Structural Formula (A): or a pharmaceutically acceptable salt thereof, wherein the variables are as defined and described herein. The invention also includes the synthesis and use of a compound of Structural Formula (A), or a pharmaceutically acceptable salt or composition thereof, e.g., in the treatment of cancer (e.g., mantle cell lymphoma), and other diseases and disorders.
1. A compound, represented by Structural Formula XII
or a pharmaceutically acceptable salt thereof, wherein:
m′ is 1 or 2;
Z 5 is —N— or —C(H)—;
R 20 is (C 1 -C 4 )alkyl, (C 1 -C 4 )haloalkyl, —O—(C 0 -C 4 alkylene)carbocyclyl, —O—(C 0 -C 4 alkylene)heterocyclyl, —C(H)(OH)-carbocyclyl, —C(H)(OH)-heterocyclyl, —C(H)(CH 3 )-carbocyclyl, —C(H)(CH 3 )-heterocyclyl, —C(O)(C 1 -C 4 )alkyl, —C(S)(C 1 -C 4 )alkyl, —C(O)(C 0 -C 4 alkylene)NR 11 R 12 , —C(S)(C 0 -C 4 alkylene)NR 11 R 12 , —S(O) 2 (C 1 -C 4 )alkyl, —S(O) 2 NR 11 R 12 or —C(O)NR 13 NR 11 R 12 , wherein:
R 11 and R 12 are each independently hydrogen, optionally substituted (C 1 -C 4 ) alkyl, optionally substituted carbocyclyl, or optionally substituted heterocyclyl; or
R 11 and R 12 are taken together with the nitrogen atom to which they are commonly attached to form an optionally substituted heterocyclyl; and
R 13 is hydrogen or optionally substituted (C 1 -C 4 )alkyl;
each R 21 , if present, is independently halo;
q is 0, 1, 2, 3 or 4;
each of Z 6 and Z 7 is independently —N— or —C(H)—, wherein no more than one of Z 6 and Z 7 is nitrogen;
each R 22 , if present, is independently halo, cyano, (C 1 -C 3 )alkyl, halo(C 1 -C 3 )alkyl, hydroxy, (C 1 -C 3 )alkoxy or halo(C 1 -C 3 )alkoxy; and
q′ is 0, 1, 2 or 3.
2. The compound of claim 1 , wherein q is 0, 1 or 2.
3. The compound of claim 1 , wherein R 21 , for each occurrence and if present, is fluoro.
4. The compound of claim 1 , wherein R 20 is —C(O)(C 0 -C 4 alkylene)NR 11 R 12 or —C(S)(C 0 -C 4 alkylene)NR 11 R 12 , wherein R 11 and R 12 are taken together with the nitrogen atom to which they are commonly attached to form an optionally substituted (C 3 -C 7 )heterocyclyl having 1 or 2 heteroatoms independently selected from nitrogen, oxygen and sulfur.
5. The compound of claim 1 , wherein the heterocyclyl formed by R 11 and R 12 taken together with the nitrogen atom to which they are commonly attached is optionally substituted with 1, 2, 3 or 4 substituents independently selected from halo, hydroxyl, halo(C 1 -C 3 )alkyl, (C 1 -C 3 )alkyl and (C 1 -C 3 )alkoxy.
6. The compound of claim 1 , wherein Z 5 is —C(H)—.
7. The compound of claim 1 , wherein Z 5 is —N—.
8. The compound of claim 1 , wherein the heterocyclyl formed by R 11 and R 12 taken together with the nitrogen atom to which they are commonly attached is optionally substituted with 1 or 2 substituents independently selected from halo, (C 1 -C 3 )alkyl, halo(C 1 -C 3 )alkyl, hydroxy, (C 1 -C 3 )alkoxy and halo(C 1 -C 3 )alkoxy.
9. The compound of claim 1 , represented by Structural Formula XI:
or a pharmaceutically acceptable salt thereof.
10. A compound selected from any one of the compounds in Table 1, or a pharmaceutically acceptable salt thereof.
11. A pharmaceutical composition comprising:
a compound of claim 1 , or a pharmaceutically acceptable salt thereof; and
a pharmaceutically acceptable carrier.
12. A method of treating cancer in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of a compound of claim 1 .
13. The method of claim 12 , wherein the cancer is lymphoma.
14. The method of claim 12 , wherein the cancer is cervical cancer.
15. The method of claim 12 , wherein the cancer is mantle cell lymphoma.
16. A compound represented by the following structural formula:
or a pharmaceutically acceptable salt thereof.