Methods of forming ciclopirox or derivatives thereof in a subject by administration of prodrug

Patent metadata

Field	Value
Publication number	US-9545413-B2
Application number	US-201514966323-A
Country	US
Kind code	B2
Filing date	Dec 11, 2015
Priority date	Dec 2, 2010
Publication date	Jan 17, 2017
Grant date	Jan 17, 2017

Abstract

A method of forming a compound in a subject can include: providing a composition having a prodrug compound represented by a structure of Formula 1 or stereoisomer thereof or pharmaceutically acceptable salt thereof; and administering the composition to a subject such that the prodrug compound has a phosphoryloxyalkyl prodrug moiety removed therefrom to form the compound in the subject and to form the separate phosphoryloxyalkyl compound. The prodrug can be included in a pharmaceutical composition for use in treatment of fungus, various cancers (e.g., bladder, breast, etc.), dermatitis, superficial mycoses; inflammation, tinea pedis, tinea cruris, and tinea corporis, Trichophyton rubrum, Trichophyton mentagrophytes, Epidermophyton floccosum , and Microsporum canis , candidiasis (moniliasis), Candida albicans , tinea (pityriasis) vesicolor, Malassezia furfur , acute myeloid leukemia, acute lymphoid leukemia, chronic myelogenous leukemia, lymphoma or multiple myeloma.

First claim

The invention claimed is:

1. A method of forming an active compound in a subject, the method comprising:
providing a composition having a prodrug compound represented by a structure of Formula 1 or stereoisomer thereof or pharmaceutically acceptable salt thereof; and
administering the composition to a subject such that the prodrug compound has a phosphoryloxyalkyl prodrug moiety removed therefrom to form the active compound and a phosphoryloxyalkyl compound in the subject,

wherein:
R 1 is a short aliphatic;
R 2 -R 12 each include hydrogen;
R 13 -R 14 each independently include one or more of a positive ion, sodium ion, hydrogen, straight aliphatics, branched aliphatics, cyclic aliphatics, substituted aliphatics, unsubstituted aliphatics, saturated aliphatics, aromatics or substituted aromatics, hetero;
n is 1; and
m is 1.

2. The method of claim 1 , the prodrug compound is represented by a structure of Formula 2 or stereoisomer thereof or pharmaceutically acceptable salt thereof

3. The method of claim 1 , the prodrug compound is represented by a structure of Formula 3 or stereoisomer thereof or pharmaceutically acceptable salt thereof

4. The method of claim 1 , the prodrug compound is represented by a structure of Formula 4 or stereoisomer thereof or pharmaceutically acceptable salt thereof

5. The method of claim 1 , the prodrug compound is represented by a structure of Formula 5 or stereoisomer thereof or pharmaceutically acceptable salt thereof

6. The method of claim 1 , the prodrug compound is represented by a structure of Formula 6 or stereoisomer thereof or pharmaceutically acceptable salt thereof

7. The method of claim 1 , the prodrug compound is represented by a structure of Formula 7 or stereoisomer thereof or pharmaceutically acceptable salt thereof

8. The method of claim 1 , the prodrug compound is represented by a structure of Formula 8 or stereoisomer thereof or pharmaceutically acceptable salt thereof

9. The method of claim 1 , the prodrug compound is represented by a structure of Formula 9 or stereoisomer thereof or pharmaceutically acceptable salt thereof

10. The method of claim 1 , the prodrug compound is represented by a structure of Formula 10 or stereoisomer thereof or pharmaceutically acceptable salt thereof

11. The method of claim 1 , wherein the pharmaceutical composition comprises the compound and a pharmaceutically acceptable carrier.

12. The method of claim 1 , wherein the composition is administered in an amount to provide 6-cyclohexyl-1-hydroxy-4-methylpyridin-2(1H)-one as the active compound.

13. The method of claim 1 , wherein the phosphoryloxyalkyl prodrug moiety is enzymatically cleaved from the prodrug compound so as to form the compound.

14. The method of claim 1 , wherein the compound is formed in an amount sufficient for disrupting DNA repair in a cell in the subject.

15. The method of claim 1 , wherein the compound is formed in an amount sufficient for disrupting cell division in the subject.

16. The method of claim 1 , wherein the compound is formed in an amount sufficient for disrupting intranuclear transport in a cell in the subject.

Assignees

• Univ Kansas
• Univ Kansas

Inventors

• Tanol Mehmet
• Weir Scott

Classifications

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61P29/00

  Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID] · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• A61P31/10

  Antimycotics · CPC title

• A61P35/02

  specific for leukemia · CPC title