Prodrug compositions and methods for using the same in treating cancer and malaria
View Patent ↗Methods and compositions for treating disease caused by increased iron levels are disclosed Fluoregenic compounds and methods of using the same are also described.
1. A prodrug having the formula
wherein,
X is —O—;
Z 1 together with L 1 is a drug;
L 1 is —N(R 6 )—, —O— or —OC(O)—;
L 2 is a bond, substituted or unsubstituted alkylene, substituted or unsubstituted heteroalkylene, —C(O)N(R 7 )— or —N(R 7 )—C(O)—;
L 3 is —OC(O)— or a bond, with the proviso that if L 1 is —OC(O)—, then L 3 is a bond;
R 1a and R 1b are independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;
R 2 is hydrogen or an electron withdrawing moiety;
R 3 is substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;
R 4 and R 5 are joined together to form a ring moiety having at least 6 atoms, said ring moiety selected from substituted or unsubstituted cycloalkyl or substituted or unsubstituted heterocycloalkyl;
R 6 is hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; and
R 7 is hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;
wherein said drug is an anti-malarial drug or anti-cancer drug capable of treating malaria or cancer that is associated with a cell or organism having increased Fe II levels compared to Fe II levels in mammalian plasma.
2. The prodrug of claim 1 , wherein R 6 is hydrogen, unsubstituted alkyl or unsubstituted heteroalkyl.
3. The prodrug of claim 1 , wherein R 6 is hydrogen or unsubstituted C 1 -C 10 alkyl.
4. The prodrug of claim 1 , wherein R 6 is hydrogen.
5. The prodrug of claim 1 , wherein L 3 is a bond.
6. The prodrug of claim 1 , wherein L 3 is —O—C(O)— and L 1 is —NH— or —O—.
7. The prodrug of claim 1 , wherein L 1 is —NR 6 — and R 6 is hydrogen.
8. The prodrug of claim 1 , wherein R 1a , R 1b , and R 2 are hydrogen.
9. The prodrug of claim 1 , wherein R 1a is methyl or phenyl and R 2 is cyano.
10. The prodrug of claim 1 , wherein R 1a is phenyl and R 2 is cyano.
11. The prodrug of claim 1 , wherein R 1a is phenyl and R 2 is H.
12. The prodrug of claim 1 , wherein L 2 has the formula —(CH 2 ) w —C(O)NH—(CH 2 ) z — or —(CH 2 ) w —NHC(O)—(CH 2 ) z —, and R 3 is substituted or unsubstituted heterocycloalkyl, or substituted or unsubstituted heteroaryl, wherein w and z are independently integers from 0 to 20.
13. The prodrug of claim 12 , wherein R 3 is morpholino, and w and z are independently integers from 1 to 5.
14. The prodrug of claim 1 , wherein R 4 and R 5 are joined together to form a substituted or unsubstituted adamantyl, or substituted or unsubstituted cyclohexyl.
15. The prodrug of claim 1 , wherein R 4 and R 5 are joined together to form a substituted or unsubstituted adamantyl.
16. The prodrug of claim 1 , wherein the drug is an anti-cancer drug.
17. The prodrug of claim 1 , wherein the drug is an anti-malarial drug.
18. A method of treating a mammalian disease that is associated with a cell or organism having increased Fe II levels compared to Fe II levels in mammalian plasma, said method comprising administering an effective amount of a compound to a patient in need of such treatment, said compound being the prodrug of claim 1 .