HMOX1 inducers
The present invention is related to compounds of structure (I) as heme oxygenase 1 (HMOX 1) inducers. The present invention is also related a method of controlling the activity or the amount, or both the activity and the amount, of heme-oxygenase 1 in a mammalian subject. The definitions of the variables are provided herein.
1. A compound represented by structural formula (III-B):
or a pharmaceutically acceptable salt thereof, wherein
R 1 is —C(═O)NH(C 1 -C 4 )alkyl optionally substituted with —OH, —NH 2 , —(C 1 -C 4 )-alkoxy, or —(C 1 -C 4 )hydroxyalkoxy, and
R 2 is H.
2. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein
R 1 is —C(═O)NH(C 1 -C 4 )alkyl substituted with —OH.
3. The compound of claim 2 , wherein the compound is:
2-(benzo[d]oxazol-2-ylamino)-N-(2-hydroxyethyl)-1-methyl-1H-benzo[d]imidazole-5-carboxamide or a pharmaceutically acceptable salt thereof.
4. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein
R 1 is —C(═O)NH(C 1 -C 4 )alkyl substituted with —NH 2 .
5. The compound of claim 4 , wherein the compound is:
N-(2-aminoethyl)-2-(benzo[d]oxazol-2-ylamino)-1-methyl-1H-benzo[d]imidazole-5-carboxamide or a pharmaceutically acceptable salt thereof.
6. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein
R 1 is —C(═O)NH(C 1 -C 4 )alkyl substituted with —(C 1 -C 4 )hydroxyalkoxy.
7. The compound of claim 6 , wherein the compound is:
2-(benzo[d]oxazol-2-ylamino)-N-(2-(2-hydroxyethoxy)ethyl)-1-methyl-1H-benzo[d]imidazole-5-carboxamide or a pharmaceutically acceptable salt thereof.
8. A pharmaceutical composition comprising a pharmaceutically acceptable carrier or diluent and the compound of claim 1 , or a pharmaceutically acceptable salt thereof.
9. A method of increasing the activity of or the amount of HMOX-1 in a human subject comprising: administering to a human subject an effective amount of the compound of claim 1 , or a pharmaceutically acceptable salt thereof.
10. A method of activating transcription factor Nrf2 in a human subject comprising: administering to a human subject an effective amount of a compound of claim 1 , or a pharmaceutically acceptable salt thereof.
11. A method of reducing the amount of ROS in a human subject comprising: administering to a human subject an effective amount of the compound of claim 1 , or a pharmaceutically acceptable salt thereof.