Oxysterols for activation of hedgehog signaling, osteoinduction, antiadipogenesis, and Wnt signaling

1. A compound having Formula I,

wherein q is a single bond or a double bond,

wherein t is a single bond,

wherein at least one of q and t is a single bond,

wherein M is selected from the group consisting of hydrogen (—H), hydroxy (—OH), formoxy (—O(C═O)H), acyloxy (—O(C═O)—C 1-6 alkyl), alkoxy (—O—C 1-6 alkyl), sulfhydryl (—SH), alkylthio (—S—C 1-6 alkyl), amino (—NH 2 ), methylamino (—NHCH 3 ), alkylamino (—NH—C 1-6 alkyl), formamido (—NH(C═O)H), acetamido (—NH(C═O)CH 3 ), and alkylamido (—NH(C═O)—C 1-6 alkyl),

wherein E is C 1-6 alkyl,

wherein R 2 is selected from the group consisting of C 2-6 alkyl, C 2-6 alkenys, C 8-12 phenalkyl, thiophene-substituted C 5-11 alkyl, C 5-12 aralkenyl, C 5-12 aralkynyl, halogen-substituted C 4-12 aralkyl, halogen-substituted C 5-12 aralkenyl halogen-substituted C 5-12 aralkynyl, alkyl-substituted C 5-18 aralkyl alkyl-substituted C 6-18 aralkenyl, alkyl-substituted C 6-18 aralkynyl, hydroxy-substituted C 6 alkyl, and hydroxy-substituted C 2-6 alkenyl,

wherein when q is a single bond, M is hydroxy, and E is methyl, then R 2 is not 4-methylpentyl vinyl, 1-hydroxzy-4-methylpentyl, 3-hydroxy-3-methylbutyl, 4-hydroxy-4methylpentyl 1,4-dihydroxy-4-methylpentyl, 1,5-dihydroxy-4-methylpentyl, or 2-phenylethenyl,

wherein when q is a single bond, M is hydroxy, and E is methyl, then R 2 is not 4-methylpentyl or 4-methyl-pent-3-enyl,

wherein when q is a double bond, M is hydrogen, and E is methyl, then R 2 is not ethyl, vinyl, n-propyl, allyl, 1-propenyl, n-butyl, t-butyl, 1-methylpropyl, n-pentyl, 3-methylbutyl, 3-methylpentyl, 4-methylpentyl, 4-methylpent-3-enyl, 4-methylpent-4-enyl, 1-hydroxy-4-methylpentyl, 4-hydroxy-4-methylpentyl, 4-hydroxy-4-methylpent-1-enyl, 4-hydroxy-4-methylpent-2-enyl, 1,4-dihydroxy-4-methylpentyl, 1-(2-pyridinyl)ethyl, or 3 -methyl-4-hydroxybutyl,

wherein when q is a double bond, M is hydrogen, and E is 4-methylpentyl, then R 2 is not hydroxymethyl,

wherein when q is a double bond and M is hydrogen, then R 2 is not methyl-substituted benzyl,

wherein the compound is not

 and

wherein the compound is inductive of a biological response in a mammalian cell, the response selected from the group consisting of stimulated osteoblastic differentiation, inhibited adipocyte differentiation, stimulated cartilage formation, stimulated hair growth, and/or stimulated angiogenesis.

2. The compound of claim 1 ,

wherein the compound is selected from the group consisting of

3. A bioactive composition comprising a compound of claim 1 and a pharmaceutically acceptable carrier.

4. The bioactive composition of claim 3 , further comprising at least one additional agent, selected from the group consisting of parathyroid hormone, sodium fluoride, insulin-like growth factor I (ILGF-I), insulin-like growth factor II (ILGF-II), transforming growth factor beta (TGF-β), a cytochrome P450 inhibitor, an osteogenic prostanoid, bone morphogenetic protein 2 (BMP 2), bone morphogenetic protein 4 (BMP 4), bone morphogenetic protein 7 (BMP 7), and bone morphogenetic protein 14 (BMP 14).

5. The compound of claim 1 , wherein q is a single bond.

6. The compound of claim 5 , wherein E is —CH 3 .

7. The compound of claim 6 , wherein M is —OH or —O(C═O)CH 3 .

8. The compound of claim 7 , wherein R 2 is selected from the group consisting of C 2-6 alkyl, C 2-6 alkenyl, C 8-12 phenalkyl, thiophene-substituted C 5-11 alkyl, C 5-12 aralkynyl, and hydroxy-substituted C 6 alkyl.

9. The compound of claim 8 , wherein the compound is

10. The compound of claim 8 , wherein the compound is

11. The compound of claim 1 , wherein q is a double bond.

12. The compound of claim 11 , wherein E is —CH 3 .

13. The compound of claim 12 , wherein M is hydrogen.

14. The compound of claim 13 , wherein R 2 is selected from the group consisting of C 2-6 alkenyl, C 8-12 phenalkyl, thiophene-substituted C 5-11 alkyl, C 5-12 aralkynyl, and halogen-substituted C 4-12 aralkyl.