Hydroxy sulfonate of quinone compounds and their uses

• US 7,790,765 B2
• Filed: 04/30/2008
• Issued: 09/07/2010
• Est. Priority Date: 04/30/2007
• Status: Active Grant

• Current Assignee: ArQule, Inc. (Merck & Co., Inc.)
• Original Assignee: ArQule, Inc. (Merck & Co., Inc.)
• Inventors: Volckova, Erika, Lowe, Deirdre, Bartis, Judit, Tandon, Manish, Redmon, Martin P.
• Primary Examiner(s): DENTZ, BERNARD I
• Application Number:
  US12/150,914
• Publication Number:
  US 20090028952A1
• Time in Patent Office: 860 Days
• Field of Search: 549/389, 514/454
• US Class Current: 514/454
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 35/02 specific for leukemia
• CPC Class Codes: A61P 35/04 specific for metastasis
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07D 311/92 Naphthopyrans; Hydrogenated naphthopyrans
• CPC Class Codes: Y02A 50/30 Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Abstract

The present invention provides sodium 6-hydroxy-2,2-dimethyl-5-oxo-3,4,5,6-tetrahydro-2H-benzo(h)chromene-6-sulfonate, and its synthesis and uses in the treatment of cancer.

Claims

1. A compound of formula I:

2. The compound of claim 1 wherein the G is selected from the group consisting of H⁺, Na⁺, K⁺, Li⁺, and Ca²⁺.

3. The compound of claim 1 wherein the compound is

4. The compound of claim 1 wherein the purity of the compound is 50% or more, 60% or more, 70% or more, 80% or more, 90% or more, 95% or more, or 99% or more.

5. The compound of claim 1, wherein the compound is in crystalline form, lyophilized form, or aqueous solution.

6. A pharmaceutical composition comprising the compound of claim 1.

7. The pharmaceutical composition of claim 6 wherein the concentration of the compound is in the range from 0.01 M to 0.1 M.

8. The pharmaceutical composition of claim 6 further comprising a pharmaceutically acceptable solubilizing carrier molecule.

9. The pharmaceutical composition of claim 8 wherein said solubilizing carrier molecule is hydroxypropyl-β

-cyclodextrin (HPβ

CD).

10. The pharmaceutical composition of claim 9 wherein the concentration of HPβ

CD is in the range from 1% to 20%.

11. The pharmaceutical composition of claim 6 further comprising an antioxidant.

12. The pharmaceutical composition of claim 11 wherein the antioxidant is selected from the group consisting of sodium thiosulfate, ethylene diamine tetraacetic acid (EDTA), and Butylated hydroxytoluene (BHT).

13. The pharmaceutical composition of claim 6 further comprising polyethylene glycol (PEG) or ethanol.

14. The pharmaceutical composition of claim 6 further comprising a buffer.

15. The pharmaceutical composition of claim 6 wherein the pH of the pharmaceutical composition is from 3 to 7.

16. A method of treating a cell proliferative disorder, said method comprising administering to a subject in need thereof a therapeutically effective amount of the compound of claim 1, or a pharmaceutically acceptable salt thereof, or a prodrug or metabolite thereof, in combination with a pharmaceutically acceptable carrier, wherein said cell proliferative disorder is treated.

17. A synthetic process comprising mixing β

-lapachone, and a bisulfate agent in an aqueous solution.

18. The process of claim 17 wherein the β

-lapachone is in the form of crystalline particles wherein 90% of the particles have a diameter of 200 μ

m or lower, 100 μ

m or lower, 30 μ

m or lower, or 10 μ

m or lower.