| PATENT NUMBER | This data is not available for free |
| PATENT GRANT DATE | February 10, 2004 |
| PATENT TITLE |
Carboxylated heterocyclic compounds and methods of synthesis |
| PATENT ABSTRACT | Compositions of the present invention comprise carboxylated heterocyclic compounds, including carboxyflosequinan. The methods of the present invention also comprise the synthesis of carboxyflosequinan |
| PATENT INVENTORS | This data is not available for free |
| PATENT ASSIGNEE | This data is not available for free |
| PATENT FILE DATE | October 28, 2002 |
| PATENT PARENT CASE TEXT | This data is not available for free |
| PATENT CLAIMS |
What is claimed is: 1. A composition comprising 3-carboxymethylsulfinyl-7-fluoro-3-methyl-4-quinolone having the corresponding structure: ##STR8## 2. A pharmaceutically acceptable formulation comprising said composition of claim 1. 3. The formulation of claim 2, wherein said formulation is a salt, wherein said salt is capable of administration to a subject. 4. The formulation of claim 2 further comprising a binder. 5. The formulation of claim 2 further comprising a filler. 6. The formulation of claim 2 further comprising a carrier. 7. The formulation of claim 2 further comprising a preservative. 8. The formulation of claim 2 further comprising a stabilizing agent. 9. The formulation of claim 2 further comprising an emulsifier. 10. The formulation of claim 2 further comprising a buffer. 11. The formulation of claim 2 further comprising an excipient. -------------------------------------------------------------------------------- |
| PATENT DESCRIPTION |
FIELD OF THE INVENTION The present invention teaches compositions comprising carboxylated heterocyclic compounds and the synthesis of the same. BACKGROUND A variety of heterocyclic compounds have been described as having various pharmaceutical applications. However, the synthesis of such compounds, especially on a large scale, is often labor-intensive, expensive and time consuming. What is needed therefore, is a simplified and economical method for the synthesis and purification of heterocyclic compounds. SUMMARY OF THE INVENTION The present invention relates to compositions comprising carboxyflosequinan and the synthesis of the same. In one embodiment, the present invention teaches a carboxylated heterocyclic compound corresponding to 3-carboxymethylsulfinyl-7-fluoro-1-methyl-4-quinolone (carboxyflosequinan) and derivatives thereof. In one embodiment, the present invention teaches providing, 3-cyanomethylthio-7-fluoro-1-methyl-4-quinolone and a first acid followed by the reaction of said 3-cyanomethylthio-7-fluoro-1-methyl-4-quinolone and first acid under conditions such that 3-carboxymethylthio-7-fluoro-1-methyl-4-quinolone is produced. In another embodiment the present invention further contemplates the reaction of 3-carboxymethylthio-7-fluoro-1-methyl-4-quinolone with a second acid and a peroxide under conditions such that 3-Carboxymethylsulfinyl-7-fluoro-1- methyl-4-quinolone is produced. DESCRIPTION OF THE DRAWINGS FIG. 1 shows the chemical structure of 3-carboxymethylsulfinyl-7-fluoro-1-methyl-4-quinolone. FIG. 2 displays a scheme for the synthesis of 3-carboxymethylsulfinyl-7-fluoro-1-methyl-4-quinolone. FIG. 3 depicts the results of enzyme (PKC) inhibition assays with 3-carboxymethylsulfinyl-7-fluoro-1-methyl-4-quinolone. DEFINITIONS As used herein carboxyflosequinan refers to the chemical composition designated as 3-carboxymethylsufinyl-7-fluoro-3-methyl-4-quinolone having the chemical structure corresponding to: ##STR1## As used herein, the phrase "flosequinan" and a "a racemic mixture of flosequinan" refers to 7-fluoro-1-methyl-3-(methylsulphinyl)-4(1H)-quinolinone which may also be described as 7-fluoro-1-methyl-3-(methylsulfinyl)-4(1H)-quinolone) and as 7-fluoro-1-methyl-3-methylsulfinyl-4-quinolone having the chemical structure of: ##STR2## As used herein, "room temperature", "RT" or "ambient temperature" is approximately 18.degree. C. to 25.degree. C. As used herein, "overnight" is approximately 8 hours, more preferably 12 hours, more typically 17 hours, but can be up to approximately 30 hours. As used herein, a "heterocyclic" compound refers to a compound comprising a ring composed of atoms of more than one kind. As used herein, a "catalyst" refers to a substance that, when added to a reaction mixture, changes (e.g. speeds up) the rate of attainment of equilibrium in the system without itself undergoing a permanent chemical change. Examples of suitable catalysts contemplated for use in the present invention include, but are not limited to, antimony chloride and carbon tetrabromide. As used herein, a "solvent" refers to a substance that will dissolve other substances. An "organic solvent" is an organic substance that will dissolve other substances. Examples of solvents suitable for use in embodiments of the present invention include, but are not limited to dichloromethane and acetonitrile. DETAILED DESCRIPTION OF THE INVENTION In one embodiment, the present invention describes a composition comprising carboxyflosequinan. In another embodiment, the present invention teaches methods for the synthesis of carboxyflosequinan. The present invention also contemplates the formulation of carboxyflosequinan as a pharmaceutically acceptable salt. In addition, pharmaceutical formulations of carboxyflosequinan may also contain binders, fillers, carriers, preservatives, stabilizing agents, emulsifiers, buffers and excipients as, for example, pharmaceutical grades of mannitol, lactose, starch, magnesium stearate, sodium saccharin, cellulose, and magnesium carbonate. The present invention also contemplates the administration of carboxyflosequinan as a pharmaceutically acceptable salt or formulation. The present invention also contemplates the administration of carboxyflosequinan and carboxyflosequinan formulations to a subject. Methods of producing a racemic mixture of flosequinan, as set out in U.S. Pat. Nos. 5,079,264 and 5,011,931 to MacLean et al., are hereby incorporated by reference. In one embodiment, flosequinan is prepared according to the protocol set out in Example 2. Without limiting the invention to any particular mechanism, carboxyflosequinan is an enzyme inhibitors. In a specific example, carboxyflosequinan inhibit protein kinase C (herein after PKC). This effect of carboxyflosequinan on enzyme activity, more particularly on PKC, has utility in therapeutics. EXPERIMENTAL The following examples serve to illustrate certain preferred embodiments and aspects of the present invention and are not to be construed as limiting the scope thereof. In the experimental disclosure which follows, the following abbreviations apply: eq (equivalents); M (Molar); .mu.M (micromolar); N (Normal); mol (moles); mmol (millimoles); tmol (micromoles); nmol (nanomoles); g (grams); mg (milligrams); L (liters); ml (milliliters); .degree. C. (degrees Centigrade). All bracketed numbers [e.g. "(1)"] after the chemical name of a compound, refer to the corresponding chemical structure as designated by the same bracketed number in FIG. 1. All NMR spectra were recorded using Varian-Gemini 300 MHz Spectrometer |
| PATENT EXAMPLES | available on request |
| PATENT PHOTOCOPY | available on request |
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