7-dehydrocholesterol derivatives and methods using same

1. A compound of formula (I), or a salt or solvate thereof:

wherein in (I):

R 1 is CR 5 or N, wherein:

if R 1 is CR 5 , then

R 3 is selected from the group consisting of —O(CR 5 ) n R 6 , —O(CR 5 ) n alkoxy, —O(CR 5 ) n+1 OH, —OC(═O)(CR 5 ) n R 6 and —OC(═O)(CR 5 ) n OR 5 and

if R 1 is N, then R 3 is selected from the group consisting of —O(CR 5 ) n R 6 , —O(CR 5 ) n+1 OR 5 , —OC(═O)(CR 5 ) n R 6 and —OC(═O)(CR 5 ) n OR 5 ;

R 2 is selected from the group consisting of O, S, C(R 4 ) 2 , and N(R 4 );

each occurrence of R 4 is independently selected from the group consisting of H, alkyl, substituted alkyl, cycloalkyl, substituted cycloalkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, aryl, substituted aryl, arylalkyl, substituted arylalkyl, heteroaryl, substituted heteroaryl, heteroarylalkyl, substituted heteroarylalkyl, OR 5 , and N(R 5 ) 2 ;

each occurrence of R 5 is independently selected from the group consisting of H, alkyl, substituted alkyl, cycloalkyl, substituted cycloalkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, aryl, substituted aryl, arylalkyl, substituted arylalkyl, heteroaryl, substituted heteroaryl, heteroarylalkyl, and substituted heteroarylalkyl;

R 6 is selected from the group consisting of F, Cl, Br, I, mesyl, tosyl, —OSi(R 5 ) 3 , —C(═O)OR 5 , and —C(═O)R 5 ;

the dotted line is a single or double bond; and,

n is an integer ranging from 1 to 5.

2. A compound of formula (I), or a salt or solvate thereof:

wherei in (I)

R 1 is N;

R 2 is N(R 4 );

R 3 is selected from the group consisting of —O(CR 5 ) n R 6 , —OC(═O)(CR 5 ) n OR 5 , and —OC(═O)C(R 5 )═C(R 5 ) 2 ;

R 4 is independently selected from the group consisting of H, alkyl, substituted alkyl, cycloalkyl, substituted cycloalkyl, alkenyl, substituted arylalkyl, heteroaryl, substituted heteroaryl, heteroarylalkyl, substituted heteroarylalkyl, OR 5 , and N(R 5 ) 2 ;

each occurrence of R 5 is independently selected from the group consisting of H, alkyl, substituted alkyl, cycloalkyl, substituted cycloalkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkenyl, aryl, substituted aryl, arylalkyl, substituted arylalkyl, heteroaryl, substituted heteroaryl, heteroarylalkyl, and substituted heteroarylalkyl;

R 6 is selected from the group consisting of F, Cl, Br, I, mesyl, tosyl, —OSi(R 5 ) 3 , —C(═O)OR 5 , and —C(═O)R 5;

the dotted line is a single or double bond; and,

n is an integer from 1-10.

3. The compound of claim 2 , wherein the compound of formula (I) is selected from the group consisting of:

4. A compound of formula (I), or a salt or solvate thereof:

wherein in (I):

R 1 is CR 5;

R 2 is selected from the group consisting of O, S, C(R 4 ) 2 , and N(R 4 );

R 3 is selected from the group consisting of —N(R 5 ) 2 , —NO, —N(R 5 )N(R 5 ) 2 , R 6 , —N(R 5 )—OR 5 , —NH-C(═O)R 5 , alkoxy, —OSO 3 H, —O(CR 5 ) n alkoxy, —O(CR 5 ) n+1 OH, —OC(═O)(CR 5 ) n R 6 , —OC(═O)(CR 5 ) n OR 5 , and —OC(═O)C(R 5 )═C(R 5 ) 2 or R 3 is selected from the group consisting of ═O and ═S, and H* is omitted;

each occurrence of R 4 is independently selected from the group consisting of H, alkyl, substituted alkyl, cycloalkyl, substituted cycloalkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, aryl, substituted aryl, arylalkyl, substituted arylalkyl, heteroaryl, substituted heteroaryl, heteroarylalkyl, substituted heteroarylalkyl, OR 5 , and N(R 5 ) 2 ;

each occurrence of R 5 is independently selected from the group consisting of H, alkyl, substituted alkyl, cycloalkyl, substituted cycloalkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, aryl, substituted aryl, arylalkyl, substituted alkenyl, heteroaryl, substituted heteroaryl, heteroarylalkyl, and substituted heteroarylalkyl;

R 6 is selected from the group consisting of F, Cl, Br, I, mesyl, tosyl, —OSi(R 5 ) 3 , —C(═O)OR 5 , and —C(═O)R 5 ;

the dotted line is a single or double bond; and,

n is an integer from 1 to 10.

5. The compound of claim 4 , wherein R 5 is selected from the group consisting of H, alkyl, substituted alkyl, cycloalkyl, substituted cycloalkyl, arylalkyl, substituted arylalkyl, heteroarylalkyl, and substituted heteroarylalkyl.

6. The compound of claim 4 , wherein R 3 is selected from the group consisting of R 6 , —O(CR 5 ) n R 6 , OC(═O)(CR 5 ) n R 7 , and OC(═O)C(R 5 )═C(R 5 ) 2 ; or R 3 is selected from the group consisting of ═O and ═S, and H* is omitted.

7. The compound of any one of claims 1 , 2 and 4 , wherein the salt is an acid addition salt and is selected from the group consisting of sulfate, hydrogen sulfate, hydrochloric, hydrobromic, hydriodic, nitric, carbonic, sulfuric, phosphoric, formic, acetic, propionic, succinic, glycolic, gluconic, lactic, malic, tartaric, citric, ascorbic, glucuronic, maleic, fumaric, pyruvic, aspartic, glutamic, benzoic, anthranilic, 4-hydroxybenzoic, phenylacetic, mandelic, embonic (pamoic), methanesulfonic, ethanesulfonic, benzenesulfonic, pantothenic, trifluoromethanesulfonic, 2-hydroxyethanesulfonic, p-toluenesulfonic, sulfanilic, cyclohexylaminosulfonic, stearic, alginic, β-hydroxybutyric, salicylic, galactaric and galacturonic acid, and any combinations thereof.

8. The compound of any one claims 1 , 2 and 4 wherein the salt is a base addition salt and is selected from the group consisting of calcium, magnesium, potassium, sodium, ammonium, zinc, a basic amine salt, and any combinations thereof.

9. A pharmaceutical composition comprising the compound of any one of claims 1 , 2 and 4 and a pharmaceutically acceptable carrier.

10. The composition of claim 9 , further comprising at least one additional chemotherapeutic agent selected from the group consisting of alkylating agents; nitrosoureas; antimetabolites; antitumor antibiotics; plant alkyloids; taxanes; hormonal agents; anti-angiogenesis agents, and miscellaneous agents.

11. The composition of claim 9 , further comprising at least one additional anti-angiogenesis agent selected from the group consisting of 2-methoxyestradiol AG3340, angiostatin, antithrombin-III, anti-VEGF antibody, VEGF antagonist, batimastat, bevacizumab, BMS-275291, CA1, canstatin, combretastatin, combretastatin-A4 phosphate, CC-5013, captopril, celecoxib, dalteparin, EMD121974, endostatin, erlotinib, gefitinib, genistein, halofuginone, ID1, ID3, IM862, omatinib mesylate, inducible protein-10, interferon-alpha, interleukin-12, lavendustin-a, LY317615, AE-941, merimastat, mapsin, medroxpregesteron acetate, Meth-1, Meth-2, Neovastat, osteopontin cleaved product, PEX, pigment epithelium growth factor, platelet growth factor 4, prolactin fragment, proliferin-related protein (PRP), PTK787/ZK222584, recombinant human platelet factor-4, restin, squalamine, SU5416, SU6668, suramin, taxol, tecogalan, thalidomide, thrombospondin, TNP-470, troponin I, vasostatin, VEGF1, VEGF-TRAP and ZD6474.

12. The composition of claim 10 , wherein the compound and the agent are co-formulated in the composition.

13. A prepackaged pharmaceutical composition comprising at least one compound of any one of claims 1 , 2 and 4 .

14. The compound of claim 2 , wherein the compound of formula (I) is

15. The compound of claim 8 , wherein the basic amine is selected from the group consisting of triethylamine, diisopropylethylamine, trimethylamine, N,N′-dibenzylethylene-diamine, chloroprocaine, choline, diethanolamine, ethylenediamine, meglumine, procaine and any combinations thereof.