Synthesis of combretastatin A-4 prodrugs and trans-isomers thereof
View Patent ↗Combretastatin A-4 has been previously selected for pre-clinical development as antineoplastic agent. However, it is essentially insoluble in water. New water soluble derivatives of combretastatin A-4 and its qualified analogs have been discovered and synthesized through a multistage process using other derivatives of combretastatin A-4 as intermediates. These water soluble derivatives are herein denominated as “Combretastatin A-4 Prodrugs”.
1. A method of inhibiting microbial growth in an animal comprising administering to an animal an effective amount of a compound Formula I:
wherein:
one of —OR 1 or —OR 2 is O − Na + , and the other is hydroxyl.
2. The method of claim 1 , wherein the compound is administered to an animal having a bacterial infection.
3. The method of claim 2 , wherein the compound is administered to an animal having a bacterial infection caused by an organism selected from the group consisting of: Stenotrophomonas maltophilia, Micrococcus luteus, Staphylococcus aureus, Escherichia coli, Enterobacter cloacae, Enterococcus faecalis, Streptococcus pneumoniae , and Neisseria gonorrhoeae.
4. The method of claim 1 , wherein the compound is administered to an animal having a fungal infection.
5. The method of claim 4 , wherein the compound is administered to an animal having a fungal infection caused by an organism selected from the group consisting of Candida albicans and Cryptococcus neoformans.
6. The method of claim 1 , wherein the compound is administered intravenously.
7. The method of claim 6 , wherein the effective amount is from about 0.1 mg/kg to about 20 mg/kg.
8. The method of claim 1 , wherein the compound is administered intramuscularly.
9. The method of claim 8 , wherein the effective amount is from about 1 mg/kg to about 50 mg/kg.
10. The method of claim 1 , wherein the compound is administered orally.
11. The method of claim 10 , wherein the effective amount is from about 5 mg/kg to about 100 mg/kg.
12. The method of claim 1 , wherein the compound is administered topically.
13. The method of claim 12 , wherein the effective amount is from about 0.01% w/w to about 50% w/w.
14. The method of claim 1 , wherein the compound is administered intravaginally, intrarectally, intraocularly or intranasally.
15. The method of claim 1 , wherein the animal is a human.