Cyclopamine analogs
The invention provides derivatives of cyclopamine having the following formula:
1. A compound having the structure:
where R is selected from the group consisting of —H, —OH, and a nitrogen protecting group,
or a pharmaceutically acceptable salt thereof.
2. The compound of claim 1 , wherein R is —OH.
3. The compound of claim 1 , wherein R is a nitrogen protecting group selected from the group consisting of formyl, chloroacetyl, trichloroacetyl, trifluoroacetyl, phenyl acetyl, benzoyl, benzamide, alkyl carbamate, aralkyl carbamate, aryl carbamate, allyl, aralkyl, alkoxymethyl, aralkoxymethyl, N-2-cyanoethyl, diarylphosphinamide, dialkylphosphinamidate, diarylphosphinamidate, and trialkylsilyl.
4. The compound of claim 3 , where the nitrogen protecting group is benzyl carbamate,
or benzoyl,
5. The compound of claim 1 , wherein R is H, and the compound is in the form of a pharmaceutically acceptable quaternary ammonium salt.
6. The compound of claim 5 , wherein the pharmaceutically acceptable salt is an inorganic acid addition salt.
7. The compound of claim 6 , where the inorganic acid addition salt is a hydrochloride salt.
8. A crystalline form of the compound of claim 7 .
9. A pharmaceutical composition comprising a compound having the structure:
where R is selected from the group consisting of —H, —OH, and a nitrogen protecting group, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient.
10. The composition of claim 9 , wherein R is —OH.
11. The composition of claim 9 , wherein R is H, and the compound is in the form of a pharmaceutically acceptable quaternary ammonium salt.
12. The composition of claim 11 , wherein the pharmaceutically acceptable salt is an inorganic acid addition salt.
13. The composition of claim 12 , where the inorganic acid addition salt is a hydrochloride salt.
14. The composition of claim 13 , wherein the composition is in liquid form.
15. The composition of claim 9 , in a form suitable for topical application.