Details for Patent: 6,204,257

Title:	Water soluble prodrugs of hindered alcohols
Abstract:	The present invention is directed to novel water-soluble prodrugs of aliphatic or aromatic hindered hydroxyl group containing pharmaceuticals.
Inventor(s):	Stella; Valentino J. (Lawrence, KS), Zygmunt; Jan J. (Longmont, CO), Georg; Ingrid Gunda (Lawrence, KS), Safadi; Muhammad S. (Nazareth, IL)
Assignee:	Universtiy of Kansas (Lawrence, KS)
Filing Date:	Aug 07, 1998
Application Number:	09/131,385
Claims:	1. A compound according to formula I: ##STR49## wherein, R--O-- is a residue of a phenol containing pharmaceutical compound, R.sup.1 Is hydrogen or an alkali metal ion or a protonated amine or a protonated amino acid, R.sup.2 is hydrogen or an alkali metal ion or a protonated amine or a protonated amino acid, and n is an integer of 1 or 2; and pharmaceutically acceptable salts thereof. 2. The compound according to claim 1, wherein said phenol-containing compound is selected from the group consisting of propofol, etoposide, and vitamin E. 3. The compound according to claim 1, wherein the alkali metal ion of R.sup.1 and R.sup.2 is each independently selected from the group consisting of sodium, potassium and lithium. 4. A compound selected from the group consist of: ##STR50## wherein Z is selected from the group consisting of hydrogen, alkali metal ion, and anine; and pharmaceutically acceptable salts thereof. 5. The compound according to claim 4, wherein each Z is independently selected from the group consisting of sodium, tromethamine, triethanolamine, triethylamine, arginine, lysine, ethanolamine and N-methylglucamine. 6. A compound according to formula IV: ##STR51## wherein, R--O-- is a residue of a phenol-containing pharmaceutical compound, Y is a phosphono protecting group, and n is an integer of 1 or2; and pharmaceutically acceptable salts thereof. 7. A compound according to claim 6, wherein said compound is selected from the group consisting of: ##STR52## wherein Y is a phosphono protecting group. 8. The compound according to claim 6, wherein said phosphono protecting group is selected from the group consisting of a benzyl group, a t-butyl group, an allyl group, and other acceptable phosphate protecting groups. 9. A pharmaceutical composition, comprising: a compound according to claim 1; and a pharmaceutically acceptable carrier. 10. A process for preparing a compound of claim 4, comprising: removing a phosphono protecting group from a compound according to one of the following formula: ##STR53## wherein Y is the phosphono protecting group; and recovering the product. 11. A method of treatment which produces an anesthetic effect comprising administering to a patient in need thereof an effective amount of a composition according to claim 1. 12. The method according to claim 11, wherein said compound is administered orally. 13. The method according to claim 11, wherein said compound is administered parenterally. 14. The compound according to formula I, ##STR54## wherein, R--O is a residue of propofol, R.sup.1 is hydrogen or an alkali metal ion or a protonated amine or a protonated amino acid, R.sup.2 is hydrogen or an alkali metal ion or a protonated amine or a protonated amino acid, and n is an integer of 1 or 2; and pharmaceutically acceptable salts thereof. 15. The compound according to claim 14, wherein the alkali metal ion of R.sup.1 and R.sup.2 is independently selected from the group consisting of sodium, potassium and lithium. 16. A compound ##STR55## wherein Z is selected from the group consisting of hydrogen, alkali metal ion and amine, and n is an integer of 1 or 2; and pharmaceutically acceptable salts thereof. 17. The compound according to claim 16, wherein Z is independently selected from the group consisting of sodium, tromethamine, triethanolamine, triethylamine, arginine, lysine, ethanolamine and N-methylaglucamine. 18. The compound according to Formula I, ##STR56## wherein R--O is a residue of propofol Y is a phosphono protecting group, and n is an integer of 1 or 2; and pharmaceutically acceptable salts thereof. 19. A compound: ##STR57## wherein Y is a phosphono protecting group. 20. The compound according to claim 19, wherein said phophonoprotecting group is selected from the group consisting of a benzyl group, a t-butyl group, an allyl group, and other acceptable phosphate protecting groups. 21. A pharmaceutical composition comprising an effective anesthetic amount of the compound according to claim 14 and a pharmaceutically acceptable carrier. 22. A method of treatment which produces an anesthetic effect comprising administering to a patient in need thereof an effective anesthetic amount of the composition of claim 21. 23. A pharmaceutical composition comprising an effective anesthetic amount of the compound according to any one of claims 15-20 and a pharmaceutically acceptable carrier. 24. A method of producing an anesthetic effect which comprises administering to a patient in need thereof an effective anesthetic amount of the compound according to any one of claims 14-20. 25. A pharmaceutical composition comprising an effective anti-cancer amount of the compound according to any one of claims 1-5, 8, 9 or 10 and a pharmaceutically acceptable carrier, wherein said pharmaceutical compound is etoposide. 26. A method of treating cancer which comprises administering to a patient in need thereof an effective anti-cancer amount of the compound according to any one of claims 1-5, 8, 9 or 10 wherein said pharmaceutical compound is etoposide. 27. A pharmaceutical composition comprising a pharmaceutical compound according to any one of claims 1-5, 8, 9 or 10 and a pharmaceutically acceptable carrier, wherein said pharmaceutical compound is vitamin E. 28. A method of treating vitamin E deficiency which comprises administering to a patient in need thereof an effective amount of the compound according to any one of claims 1-5, 8, 9 or 10, wherein said pharmaceutical compound is Vitamin E.