11-aza, 11-thia and 11-oxa sterol compounds and compositions
The invention provides compositions comprising formula 1 steroids, e.g., 16α-bromo-3β-hydroxy-5α-androstan-17-one hemihydrate and one or more excipients, including compositions that comprise a liquid formulation comprising less than about 3% v/v water. The compositions are useful to make improved pharmaceutical formulations. The invention also provides methods of intermittent dosing of steroid compounds such as analogs of 16α-bromo-3β-hydroxy-5α-androstan-17-one and compositions useful in such dosing regimens. The invention further provides compositions and methods to inhibit pathogen replication, ameliorate symptoms associated with immune dysregulation and to modulate immune responses in a subject using the compounds. The invention also provides methods to make and use these immunomodulatory compositions and formulations.
1. A compound having the structure
wherein the dotted lines are optional double bonds,
R 1 is —OH, ═O, an ester or an ether;
R 2 and R 4 independently are —OH, an ester or an ether;
R 3 is —OH, an ester, an ether or halogen;
R 5 is —CH 3 or —CH 2 OH;
R 6 is —H, —CH 3 or —CH 2 OH; and
R 8 is —S— or —NH—.
2. The compound of claim 1 wherein R 1 , R 2 and R 4 are —OH or an ester and R 3 is —OH or —Br.
3. The compound of claim 2 wherein R 5 is —CH 3 .
4. The compound of claim 3 wherein R 6 is —H or —CH 3 .
5. The compound of claim 4 wherein the compound has the structure
6. The compound of claim 5 wherein the compound has the structure
7. The compound of claim 4 wherein the compound has the structure
8. The compound of claim 1 wherein the compound has the structure
9. The compound of claim 4 wherein the compound has the structure
10. The compound of claim 1 wherein the compound has the structure
11. A pharmaceutical formulation comprising one or more excipients and a compound having the structure
wherein the dotted lines are optional double bonds,
R 1 is —OH, ═O, an ester or an ether;
R 2 and R 4 independently are —OH, an ester or an ether;
R 3 is —OH, an ester, an ether or halogen;
R 5 is —CH 3 or —CH 2 OH;
R 6 is —H, —CH 3 or —CH 2 OH; and
R 8 is —S— or —NH—.
12. The pharmaceutical formulation of claim 11 wherein R 1 , R 2 and R 4 are —OH or an ester and R 3 is —OH or —Br.
13. The pharmaceutical formulation of claim 12 wherein R 5 is —CH 3 .
14. The pharmaceutical formulation of claim 13 wherein R 6 is —H or —CH 3 .
15. The pharmaceutical formulation of claim 14 wherein the compound has the structure
16. The pharmaceutical formulation of claim 15 wherein the compound has the structure
17. The pharmaceutical formulation of claim 14 wherein the compound has the structure
18. The pharmaceutical formulation of claim 17 wherein the compound has the structure
19. The pharmaceutical formulation of claim 14 wherein the compound has the structure
20. The pharmaceutical formulation of claim 11 wherein the compound has the structure
21. A compound having the structure
wherein
R 1 is —OH, ═O, an ester or an ether;
R 2 and R 4 independently are —OH, an ester or an ether;
R 3 is —OH, an ester, an ether or halogen;
R 5 is —CH 3 or —CH 2 OH; and
R 6 is —H, —CH 3 or —CH 2 OH.
22. The compound of claim 21 wherein R 1 , R 2 and R 4 are —OH or an ester and R 3 is —OH or —Br.
23. The compound of claim 22 wherein R 5 is —CH 3 .
24. The compound of claim 23 wherein R 6 is —H or —CH 3 .
25. The compound of claim 24 wherein the compound has the structure
26. The compound of claim 25 wherein the compound has the structure
27. The compound of claim 26 wherein the compound has the structure