Small molecule transcription modulators of bromodomains
This disclosure relates generally to compounds and compositions comprising one or more indole analogs. These compounds are useful for treating diseases associated with NF-kB and p53 activity, such as cancer and inflammatory diseases.
1. A compound of formula (1):
or a pharmaceutically acceptable salt form thereof,
wherein:
Y 1 is selected from the group consisting of: H, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, halo, and OR 3 ;
Y 2 is selected from the group consisting of H, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, halo, and OR 3 ;
X 1 and X 2 are independently selected from the group consisting of: H, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, halo, —NO 2 , —OH, —O(C 1 -C 6 alkyl), —O(C 1 -C 6 haloalkyl), —S(C 1 -C 6 alkyl), —NR 1 R 2 , —NR 1 (C(O)R 2 ), —C(O)(C 1 -C 6 alkyl), —C(O)OR 1 , —C(O)NR 1 R 2 , C 5 -C 14 aryl, and C 4 -C 14 heteroaryl;
each R 1 and R 2 are independently selected from H and C 1 -C 6 alkyl;
each R 3 is independently selected from H, C 1 -C 6 alkyl, and C 5 -C 14 aryl;
n and m are independently integers from 1 to 6.
2. The compound of claim 1 , wherein Y 1 is —OR 3 or C 1 -C 6 alkyl.
3. The compound of claim 1 , wherein Y 1 is —OH or —OPh.
4. The compound of claim 1 , wherein Y 1 is CH 3 or CH 2 CH 3 .
5. The compound of claim 1 , wherein Y 2 is selected from the group consisting of H, C 1 -C 6 alkyl, and —OR 3 .
6. The compound of claim 1 , wherein Y 2 is H.
7. The compound of claim 1 , wherein X 1 and X 2 are H.
8. The compound of claim 1 , wherein the compound of formula (1) is selected from the group consisting of:
or a pharmaceutically acceptable salt form thereof.
9. A pharmaceutical composition comprising a compound of claim claim 1 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient.
10. A method for ameliorating one or more symptoms of and/or ameliorating the underlying metabolic causes of symptoms of a neurological disorder in a patient where NF-kB is implicated in the pathology of the disorder, the method comprising administering a therapeutically effective amount of a compound of claim 1 , or a pharmaceutically acceptable salt form thereof, to the patient.