7-dehydrocholesterol derivatives and methods using same
The present invention provides, in certain aspects, novel 7-dehydrocholesterol (7DHC) derivatives that are useful in treating or preventing cancer, as well as in treating or preventing uncontrolled angiogenesis, in a subject. In certain embodiments of the present invention, the subject is a human. In other aspects, the present invention provides a method of preparing compounds of the invention, or a salt or solvate thereof.
1. A method of inhibiting angiogenesis in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of at least one compound of formula (I) or a salt or solvate thereof:
wherein:
R 1 is CR 5 or N;
R 3 is selected from the group consisting of —O(CR 5 ) n R 6 , —OC(═O)(CR 5 ) n R 6 , —OC(═O)(CR 5 ) n OR 5 , and —OC(═O)C(R 5 )═C(R 5 ) 2 ;
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 10.
2. The method of claim 1 , wherein the compound of formula (I) is the compound of formula (Ia), or a salt or solvate thereof:
3. The method of claim 1 , wherein the compound of formula (I) is the compound of formula (Ib), or a salt or solvate thereof:
4. The method of claim 1 , wherein R 1 is N.
5. The method of claim 4 , wherein R 2 is N(R 4 ).
6. The method of claim 5 , wherein the compound of formula (I) is the compound of formula (Ic), or a salt or solvate thereof:
7. The method of claim 6 , wherein the compound of formula (I) is the compound of formula (Id), or a salt or solvate thereof:
8. The method of claim 1 , wherein the compound of formula (I) is selected from the group consisting of
9. The method of claim 1 , wherein the subject is further administered at least one additional anti-angiogenesis agent.
10. The method of claim 9 , wherein the compound and the at least one additional anti-angiogenesis agent are separately administered to the subject.
11. The method of claim 9 , wherein the compound and the at least one additional anti-angiogenesis agent are co-administered to the subject.
12. The method of claim 1 , wherein the subject is a mammal.
13. The method of claim 12 , wherein the mammal is a human.