SHIP1 modulators and methods related thereto
View Patent ↗Compounds of structure (I): including stereoisomers and pharmaceutically acceptable salts thereof, wherein X, R 1 , R 2 , R 3 , R 4 , R 5 , R 6 and R 7 are as defined herein. Such compounds have activity as SHIP1 modulators, and thus may be used to treat any of a variety of diseases, disorders or conditions that would benefit from SHIP1 modulation. Compositions comprising a compound of structure (I) in combination with a pharmaceutically acceptable carrier or diluent are also disclosed, as are methods of SHIP1 modulation by administration of such compounds to an animal in need thereof.
1. A compound of the following structure (I):
or a stereoisomer or pharmaceutically acceptable salt thereof, wherein:
X is O or S(O) p where p is 0, 1 or 2;
R 1 , R 2 , R 3 , R 4 , R 5 and R 6 are independently hydrogen, halogen, hydroxyl, cyano, unsubstituted or substituted alkyl, unsubstituted or substituted alkoxy, —COOR 8 , —NR 9 R 10 , —CONR 11 R 12 , —NR 13 COR 14 or —OSO 2 R 15 ;
R 7 is hydrogen; and
R 8 , R 9 , R 10 , R 11 , R 12 , R 13 , R 14 and R 15 are independently hydrogen, unsubstituted or substituted alkyl or unsubstituted or substituted alkoxy, or R 9 /R 10 or R 11 /R 12 taken together with the nitrogen to which they are attached form a heterocycle.
2. The compound of claim 1 , wherein X is O of the following structure (II):
3. The compound of claim 1 , wherein X is S(O) p of the following structure (III):
4. The compound of claim 3 , wherein p is 0 of the following structure (III-a):
5. The compound of claim 3 , wherein p is 1 of the following structure (III-b):
6. The compound of claim 3 , wherein p is 2 of the following structure (III-c):
7. The compound of claim 1 of the following stereochemistry:
8. The compound of claim 1 , wherein R 5 and R 6 are both hydrogen.
9. The compound of claim 1 , wherein R 1 and R 3 are both hydrogen.
10. The compound of claim 1 , wherein R 2 and R 4 are both hydrogen.
11. The compound of claim 1 , wherein R 1 , R 2 , R 3 and R 4 are independently hydrogen, hydroxyl, alkyl or alkoxy.
12. The compound of claim 1 , wherein R 1 , R 2 , R 3 and R 4 are independently hydrogen, hydroxyl, alkyl, alkoxy, cyano, amino, —COOH, —OSO 2 R 15 or —CONHCH 3 .
13. The compound of claim 1 , wherein at least one of R 1 , R 2 , R 3 and R 4 is —NR 9 R 10 or —CONR 11 R 12 , and wherein R 9 /R 10 or R 11 /R 12 taken together with the nitrogen to which they are attached form a heterocycle.
14. The compound of claim 1 , wherein at least one of R 1 , R 2 , R 3 and R 4 is —COOR 8 , —NR 9 R 10 , —CONR 11 R 12 , —NR 13 COR 14 , wherein R 8 , R 9 , R 10 , R 11 , R 12 , R 13 and R 14 are independently substituted alkyl or —O-(substituted alkyl), wherein the alkyl is substituted with —C(═O)R a , —C(═O)OR a , —C(═O)NR b R c , —OC(═O)NR b R c , —NR b R c , —NR a C(═O)R b , —NR a C(═O)OR b or —NR a C(═O)NR b R c , and wherein R a , R b and R c are the same or different and independently hydrogen or alkyl.
15. The compound of claim 1 , wherein at least one of R 1 , R 2 , R 3 and R 4 is substituted alkyl or —O-(substituted alkyl), wherein the alkyl is substituted with —C(═O)R a , —C(═O)OR a , —C(═O)NR b R c , —OC(═O)NR b R c , —NR b R c , —NR a C(═O)R b , —NR a C(═O)OR b or —NR a C(═O)NR b R c , and wherein R a , R b and R c are the same or different and independently hydrogen or alkyl, or R b /R c taken together with the nitrogen to which they are attached form a heterocycle.
16. A compound selected from the group consisting of:
17. A composition comprising a compound of claim 1 in combination with a pharmaceutically acceptable carrier or diluent.