Ingenol analogs, pharmaceutical compositions and methods of use thereof

1. A compound according to formula (II):

or a pharmaceutically acceptable salt thereof:

X is selected from O or N, wherein when X is O, then R 3 is absent;

R 1 is optionally present, and when present, the group:

is represented as:

and R 1 is —C(O)R 4 ;

R 2 and R 3 are independently selected from the group consisting of —H, methyl, —C(O)R 10 , —C(O)N(R 6 ) 2 , —S(O) 2 CH 3 , (C 6 )heteroaryl and (C 9 )heteroaryl, wherein when X is N, then R 2 and R 3 may be taken together to form a pyrrolidine group optionally substituted by one or more R 12 ;

R 4 is —N(R 6 ) R 7 ;

R 6 is methyl;

R 7 is phenyl optionally substituted with one or more R 13 ;

R 10 is selected from the group consisting of (C 1 -C 4 )alkyl, (C 3 -C 9 )cyclohexyl, (C 5 -C 6 )heterocycle, and phenyl, wherein the cyclohexyl, (C 5 -C 6 ) heterocycle and phenyl are optionally substituted with one or more R 11 ; and

wherein R 11 ,R 12 and R 13 are independently selected from the group consisting of methyl, methoxy, oxo, trifluoromethyl and chloro;

with the proviso that when X is O and R 2 is H, R 1 is not present.

2. The compound according to claim 1 , wherein R 6 is methyl and R 7 is aryl substituted by chloro.

3. The compound according to claim 1 , wherein R 2 is —C(O)R 10 .

4. The compound according to claim 3 , wherein R 10 is aryl or methyl.

5. The compound according to claim 1 , wherein X is N.

6. The compound according to claim 5 , wherein R 2 and R 3 together form a (C 2 -C 9 ) heteroaryl.

7. The compound according claim 1 , wherein R 1 is absent.

8. The compound according to claim 7 , wherein X is O and R 2 is H.

9. A compound selected from the group consisting of:

((1aR,2S,5R,5aS,6S,8aS,9R, 10aR)-6-(((4-chlorophenyl) (methyl)carbamoyl)oxy)- 5,5a-dihydroxy-1,1,7,9- tetramethyl-11-oxo- 1a,2,5,5a,6,9,10,10a- octahydro-1H-2,8a- methanocyclopenta[a] cyclopropa[e][10]annulen- 4-yl)methyl acetate

((1aR,2S,5R,5aS,6S,8aS, 9R,10aR)-6-(((4- chlorophenyl) (methyl)carbamoyl)oxy)- 5,5a-dihydroxy-1,1,7,9- tetramethyl-11-oxo- 1a,2,5,5a,6,9,10,10a- octahydro-1H-2,8a- methanocyclopenta [a]cyclopropa[e][10] annulen-4-yl)methyl benzoate

(1aR,2S,5R,5aS,6S,8aS, 9R,10aR)-4-((1,3- dioxoisoindolin-2- yl)methyl)-5,5a-dihydroxy- 1,1,7,9-tetramethyl-11- oxo-1a,2,5,5a,6,9,10,10a- octahydro-1H-2,8a- methanocyclopenta[a] cyclopropa[e][10]annulen- 6-yl(4-chlorophenyl) (methyl)carbamate

(1aR,2S,5R,5aS,8aS,9R, 10aR)-5,5a-dihydroxy-4- (hydroxymethyl)-1,1,7,9- tetramethyl- 1a,2,5,5a,10,10a- hexahydro-1H-2,8a- methanocyclopenta[a] cyclopropa[e][10]annulene- 6,11(9H)-dione

((1aR,2S,5R,5aR,6S,8aS, 9R,10aR)-5,5a,6- trihydroxy-1,1,7,9- tetramethyl-11-oxo- 1a,2,5,5a,6,9,10,10a- octahydro-1H-2,8a- methanocyclopenta[a] cyclopropa[e][10]annulen-4- yl)methyl (4- chlorophenyl)(methyl) Carbamate

((1aR,2S,5R,5aR,6S,8aS, 9R,10aR)-5,5a,6- trihydroxy-1,1,7,9- tetramethyl-11-oxo- 1a,2,5,5a,6,9,10,10a- octahydro-1H-2,8a- methanocyclopenta[a] cyclopropa[e][10]annulen-4- yl)methyl phenylcarbamate

((1aR,2S,5R,5aR,6S,8aS, 9R,10aR)-5,5a,6- trihydroxy-1,1,7,9- tetramethyl-11-oxo- 1a,2,5,5a,6,9,10,10a- octahydro-1H-2,8a- methanocyclopenta[a] cyclopropa[e][10]annulen-4- yl)methyl butylcarbamate

((1aR,2S,5R,5aR,6S,8aS, 9R,10aR)-5,5a,6- trihydroxy-1,1,7,9- tetramethy1-11-oxo- 1a,2,5,5a,6,9,10,10a- octahydro-1H-2,8a- methanocyclopenta[a] cyclopropa[e][10]annulen-4- yl)methyl benzylcarbamate

((1aR,2S,5R,5aR,6S,8aS, 9R,10aR)-5,5a,6- trihydroxy-1,1,7,9- tetramethyl-11-oxo- 1a,2,5,5a,6,9,10,10a- octahydro-1H-2,8a- methanocyclopenta[a] cyclopropa[e][10] annulen-4- yl)methyl cyclohexyl(methyl) Carbamate

((1aR,2S,5R,5aR,6S,8aS, 9R,10aR)-5,5a,6- trihydroxy-1,1,7,9- tetramethyl-11-oxo- 1a,2,5,5a,6,9,10,10a- octahydro-1H-2,8a- methanocyclopenta[a] cyclopropa[e][10]annulen-4- yl)methyl indoline-1- carboxylate

(1aR,2S,5R,5aS,6S,8aS, 9R,10aR)-5,5a-dihydroxy-4- (((indoline-1- carbonyl)oxy)methyl)- 1,1,7,9-tetramethyl-11- oxo-1a,2,5,5a,6,9,10,10a- octahydro-1H-2,8a- methanocyclopenta[a] cyclopropa[e][10]annulen- 6-yl indoline-1-carboxylate

(1aR,2S,5R,5aR,6S,8aS, 9R,10aR)-5,5a,6-trihydroxy- 1,1,7,9-tetramethyl-4-(((5- (trifluoromethyl)pyrimidin- 2-yl)oxy)methyl)- 1a,2,5,5a,6,9,10,10a- octahydro-1H-2,8a- methanocyclopenta[a] cyclopropa[e][10]annulen- 11-one

and pharmaceutically acceptable salts thereof.

10. A pharmaceutical composition comprising a compound according to claim 1 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient.

11. The composition of claim 10 , wherein the compound is present in an amorphous form.

12. The composition of claim 10 , wherein the composition is in a tablet form.

13. The composition of claim 10 , wherein the compound is present as a spray dried dispersion.