Tetrol steroids and esters
The invention provides compositions comprising formula 1 steroids, e.g., 16α-bromo-3β-hydroxy-5α-androstan-17-one hemihydrate and one or more excipients, typically wherein the composition comprises less than about 3% 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 (viral) replication, ameliorate symptoms associated with immune dysregulation and to modulate immune responses in a subject using certain steroids and steroid analogs. The invention also provides methods to make and use these immunomodulatory compositions and formulations.
1. A pharmaceutical formulation comprising one or more excipients and a compound having the structure
wherein the hydrogen atom at the C5-position, if present, is in the α- or β-configuration;
R 1 is —OH;
R 2 , R 3 and R 4 independently are —OH or an ester;
R 5 is —CH 3 or —CH 2 OH; and
R 6 is —H, —CH 3 or —CH 2 OH.
2. The pharmaceutical formulation of claim 1 having the structure
3. The pharmaceutical formulation of claim 2 wherein R 1 , R 2 , R 3 and R 4 are —OH.
4. The pharmaceutical formulation of claim 1 wherein R 5 and R 6 are —CH 3 .
5. The pharmaceutical formulation of claim 3 wherein R 6 is —H and R 5 is —CH 3 or —CH 2 OH.
6. The pharmaceutical formulation of claim 2 wherein R 2 and R 4 are —OH and R 3 is —OH, —O—C(O)—CH 3 , —O—C(O)—C 2 H 5 or —O—C(O)—CH 2 CH 2 CH 3 .
7. The pharmaceutical formulation of claim 1 having the structure
8. The pharmaceutical formulation of claim 7 wherein R 1 , R 2 , R 3 and R 4 are —OH and the pharmaceutical formulation is an oral formulation.
9. The pharmaceutical formulation of claim 7 wherein R 5 is —CH 2 OH.
10. The pharmaceutical formulation of claim 7 wherein R 6 is —H and R 5 is —CH 3 or —CH 2 OH.
11. The pharmaceutical formulation of claim 7 wherein R 2 and R 4 are —OH and R 3 is —OH, —O—C(O)—CH 3 , —O—C(O)—C 2 H 5 or —O—C(O)—CH 2 CH 2 CH 3 .
12. The pharmaceutical formulation of claim 11 wherein R 3 is —O—C(O)—CH 3 , —O—C(O)—C 2 H 5 or —O—C(O)—CH 2 CH 2 CH 3 .