Morphan and morphinan analogues, and methods of use
The present application relates to analogues of morphan and morphinan, compositions thereof, and methods for treating a disease or condition comprising administering an effective amount of the compounds or compositions to a subject in need thereof.
1. A compound of Formula III:
or a pharmaceutically acceptable salt thereof, wherein
R 1 is C 1 -C 6 alkyl, C 2 -C 6 alkenyl, cycloalkyl, heterocyclyl, hydroxyalkyl, or alkoxyalkyl;
R 2 and R 3 , together with the carbon atoms to which they are attached, form a 6-membered unsubstituted carbocyclic ring, or a 6-membered carbocyclic ring optionally substituted with a NR 50 R 60 group, wherein R 50 and R 60 are each independently H, alkyl, or substituted acyl;
R 4 and R 5 are each, independently, H, hydroxyl, or taken together with the carbon atom to which they are attach to, form a C═O group;
R 6 is unsubstituted or substituted C 6 -C 10 aryl, or substituted or unsubstituted heteroaryl comprising one or two 5- or 6-membered rings and 1-4 heteroatoms selected from N, O and S; and
R 7 and R 8 are each, independently, H or hydroxyl.
2. The compound of claim 1 , wherein R 1 is C 2 -C 6 alkenyl or cycloalkyl.
3. The compound of claim 2 , wherein R 1 is cyclopropyl or cyclobutyl.
4. The compound of claim 1 , wherein R 2 and R 3 , together with the carbon atoms to which they are attached form a 6-membered unsubstituted carbocyclic ring.
5. The compound of claim 1 , wherein substituted acyl is:
wherein
R 11 is linear or branched C 1 -C 6 alkyl;
R 12 is halo, C 1 -C 6 alkyl, or C 1 -C 6 alkyl alkoxy; and
R 13 is aryl or heteroaryl.
6. The compound of claim 1 , wherein R 4 and R 5 , taken together with the carbon atom to which they are attached, form a C═O group.
7. The compound of claim 1 , wherein R 4 and R 5 are each, independently, H or hydroxyl.
8. The compound of claim 1 , wherein R 6 is substituted heteroaryl comprising one or two 5- or 6-membered rings and 1-4 heteroatoms selected from N, O, and S.
9. The compound of claim 1 , wherein R 6 is unsubstituted or substituted C 6 -C 10 aryl.