Claims
- 1. A compound having a structural formula
- 2. The compound of claim 1, wherein said compound is selected from the group consisting of 2,5,7,8-tetramethyl-(2R-(4R,8R,12-trimethyltridecyl)chroman-6-yloxy)acetic acid, 2,5,7,8-tetramethyl-(2R-(4R,8R,12-trimethyltridecyl)chroman-6-yloxy)propionic acid, 2,5,7,8-tetramethyl-2R-(4R,8R,12-trimethyltridecyl)chroman-6-yloxy)valeric acid, 2,5,7,8-tetramethyl-2R-(4R,8R,12-trimethyltridecyl)chroman-6-yloxy)hexanoic acid, 2,5,7,8-tetramethyl-2R-(4R,8R,12-trimethyltridecyl)chroman-6-yloxy)octanoic acid, 2,5,8-trimethyl-(2R-(4R,8R,12-trimethyltridecyl)chroman-6-yloxy)acetic acid, 2,7,8-trimethyl-(2R-(4R,8R,12-trimethyltridecyl)chroman-6-yloxy)acetic acid, 2,8-dimethyl-(2R-(4R,8R,12-trimethyltridecyl)chroman-6-yloxy)acetic acid, 2,5,7,8-tetramethyl-2R-(4R,8R,12-trimethyltridecyl)chroman-6-yloxy)acetamide, methyl12,5,7,8-tetramethyl-2R-(4R,8R,12-trimethyltridecyl)chroman-6-yloxy)acetate, 2-(N,N-(carboxymethyl)-2(2,5,7,8-tetramethyl-(2R-(4R,8R,12-trimethyltridecyl)chroman-6-yloxy)acetic acid,2-(2,5,7,8-tetramethyl-(2R-(4R,8R,12-trimethyltridecyl)chroman-6-yloxy))ethan-1-ol, 2-(2,5,7,8-pentamethylchroman-6-yloxy)acetic acid, 2,5,7,8-tetramethyl-(2RS-(4RS,8RS,12-trimethyltridecyl)chroman-6-yloxy)acetic acid, 2,5,7,8-tetramethyl-(2R-(carboxy)chroman-6-yloxy))acetic acid, 2,5,7,8-tetramethyl-2R-(2RS,6RS, 10-trimethylundecyl)chroman-6-yloxy)acetic acid, 2,5,7,8,-tetramethyl-2R-(2,6,10-trimethyl-1,3,5,9 E:Z decatetraen)chroman-6-yloxy)acetic acid, 3-(2,5,7,8-tetramethyl-(2R-(4R,8,12-trimethyltridecyl)chroman-6-yloxy)propyl-1-ammonium chloride, 2,5,7,8-tetramethyl-(2R-(4r,8R,12-trimethyltridecyl)chroman-3-ene-6-yloxy)acetic acid, 6-(2,5,7,8-tetramethyl-(2R-(4R,8,12-trimethyltridecyl)chroman)acetic acid, 2,5,7,8,-tetramethyl-(2R-(heptadecyl)chroman-6-yloxy)acetic acid 2,5,7,8-tetramethyl-(2R-(heptyl)chroman-6-yloxy)acetic acid, 2,5,7,8,-tetramethyl-(2R-(tridecyl)chroman-6-yloxy)acetic acid, 2,5,7,8,-tetramethyl-(2R-(heptadecyl)chroman-6-yloxy)acetic acid, 2,5,7,8,-tetramethyl-2R-(4,8,-dimethyl-1,3,7 E:Z nonotrien)chroman-6-yloxy)acetic acid, E,Z,RS,RS-(phytyltrimethylbenzenethiol-6-yloxy)acetic acid (this compound 27 does not actually fit the structure of claim 1), (R)-2[(2,5,7,8-tetramethyl-2-(3 propene methyl ester)chroman-6-yloxy]acetic acid, and 2,5,7,8-tetramethyl-(2R-(propionate)chroman-6-yloxy)acetic acid.
- 3. A method for the treatment of a cell proliferative disease comprising administering to an animal a pharmacologically effective dose of a compound having a structural formula
- 4 The method of claim 3, wherein said compound is selected from the group consisting of 2,5,7,8-tetramethyl-(2R-(4R,8R,12-trimethyltridecyl)chroman-6-yloxy)acetic acid, 2,5,7,8-tetramethyl-(2R-(4R,8R,12-trimethyltridecyl)chroman-6-yloxy)propionic acid, 2,5,7,8-tetramethyl-(2R-(4R,8R,12-trimethyltridecyl)chroman-6-yloxy)butyric acid, 2,5,8-trimethyl-(2R-(4R,8R,12-trimethyltridecyl)chroman-6-yloxy)acetic acid, 2,7,8-trimethyl-(2R-(4R,8R,12-trimethyltridecyl)chroman-6-yloxy)acetic acid, 2,8-dimethyl-(2R-(4R,8R,12-trimethyltridecyl)chroman-6-yloxy)acetic acid,2-(N,N-(carboxymethyl)-2(2,5,7,8-tetramethyl-(2R-(4R,8R,12-trimethyltridecyl)chroman-6-yloxy)acetic acid, 2,5,7,8-tetramethyl-(2RS-(4RS,8RS,12-trimethyltridecyl)chroman-6-yloxy)acetic acid, 2,5,7,8-tetramethyl-2R-(2RS,6RS,10-trimethylundecyl)chroman-6-yloxy)acetic acid, 3-(2,5,7,8-tetramethyl-(2R-(4R,8,12-trimethyltridecyl)chroman-6-yloxy)propyl-1-ammonium chloride, 2,5,7,8-tetramethyl-(2R-(4r,8R,12-trimethyltridecyl)chroman-3-ene-6-yloxy)acetic acid, 2-(2,5,7,8-tetramethyl-(2R-(4R,8,12-trimethyltridecyl)chroman-6-yloxy)triethylammonium sulfate, 6-(2,5,7,8-tetramethyl-(2R-(4R,8,12-trimethyltridecyl)chroman)acetic acid, 2,5,7,8,-tetramethyl-(2R-(heptadecyl)chroman-6-yloxy)acetic acid, 2,5,7,8,-tetramethyl-2R-(4,8,-dimethyl-1,3,7 E:Z nonotrien)chroman-6-yloxy)acetic acid, and E,Z,RS,RS-(phytyltrimethylbenzenethiol-6-yloxy)acetic acid.
- 5. The method of claim 3, wherein said compound exhibits an anti-proliferative effect comprising apoptosis, DNA synthesis arrest, cell cycle arrest, or cellular differentiation.
- 6. The method of claim 3, wherein said animal is a human.
- 7. The method of claim 3, wherein said composition is administered in a dose of from about 1 mg/kg to about 60 mg/kg.
- 8. The method of claim 3, wherein administration of said composition is selected from the group consisting of oral, topical, intraocular, intranasal, parenteral, intravenous, intramuscular, or subcutaneous.
- 9. The method of claim 3, wherein said cell proliferative disease is selected from the group consisting of neoplastic diseases and non-neoplastic disorders.
- 10. The method of claim 9, wherein said neoplastic disease is selected from the group consisting of ovarian cancer, cervical cancer, endometrial cancer, bladder cancer, lung cancer, breast cancer, testicular cancer, prostate cancer, gliomas, fibrosarcomas, retinoblastomas, melanomas, soft tissue sarcomas, ostersarcomas, leukemias, colon cancer, carcinoma of the kidney, pancreatic cancer, basal cell carcinoma, and squamous cell carcinoma.
- 11. The method of claim 9, wherein said non-neoplastic disease is selected from the group consisting of psoriasis, benign proliferative skin diseases, ichthyosis, papilloma, restinosis, scleroderma, hemangioma, viral diseases, and autoimmune diseases.
- 12. The method of claim 11, wherein said autoimmune diseases are selected from the group consisting of autoimmune thyroiditis, multiple sclerosis, myasthenia gravis, systemic lupus erythematosus, dermatitis herpetiformis, celiac disease, and rheumatoid arthritis.
- 13. The method of claim 9, wherein said non-neoplastic disorders are selected from the group consisting of viral disorders and autoimmune disorders.
- 14. The method of claim 13, wherein said viral disorder is Human Immunodeficiency Virus.
- 15. The method of claim 13, wherein said autoimmune disorders are selected from the group consisting of the inflammatory process involved in cardiovascular plaque formation, ultraviolet radiation induced skin damage and disorders involving an immune component.
- 16 A pharmaceutical composition, comprising the compound of claim 3 and a pharmaceutically acceptable carrier.
- 17 The pharmaceutical composition of claim 16, wherein said compound is selected from the group consisting of 2,5,7,8-tetramethyl-(2R-(4R,8R,12-trimethyltridecyl)chroman-6-yloxy)acetic acid, 2,5,7,8-tetramethyl-(2R-(4R,8R,12-trimethyltridecyl)chroman-6-yloxy)propionic acid, 2,5,7,8-tetramethyl-(2R-(4R,8R,12-trimethyltridecyl)chroman-6-yloxy)butyric acid, 2,5,8-trimethyl-(2R-(4R,8R,12-trimethyltridecyl)chroman-6-yloxy)acetic acid, 2,7,8-trimethyl-(2R-(4R,8R,12-trimethyltridecyl)chroman-6-yloxy)acetic acid, 2,8-dimethyl-(2R-(4R,8R,12-trimethyltridecyl)chroman-6-yloxy)acetic acid, 2-(N,N-(carboxymethyl)-2(2,5,7,8-tetramethyl-(2R-(4R,8R,12-trimethyltridecyl)chroman-6-yloxy)acetic acid, 2,5,7,8-tetramethyl-(2RS-(4RS,8RS,12-trimethyltridecyl)chroman-6-yloxy)acetic acid, 2,5,7,8-tetramethyl-2R-(2RS,6RS,10-trimethylundecyl)chroman-6-yloxy)acetic acid, compound 19?, 2,5,7,8-tetramethyl-(2R-(4r,8R,12-trimethyltridecyl)chroman-3-ene-6-yloxy)acetic acid, compound 21?, compound 22?, 2,5,7,8,-tetramethyl-(2R-(heptadecyl)chroman-6-yloxy)acetic acid, 2,5,7,8,-tetramethyl-2R-(4,8,-dimethyl-1,3,7 E:Z nonotrien)chroman-6-yloxy)acetic acid, and E,Z,RS,RS-(phytyltrimethylbenzenethiol-6-yloxy)acetic acid.
- 18. A method of inducing apoptosis of a cell, comprising the step of contacting said cell with a pharmacologically effective dose of a compound having a structural formula
- 19. The method of claim 18, wherein said compound is selected from the group consisting of 2,5,7,8-tetramethyl-(2R-(4R,8R,12-trimethyltridecyl)chroman-6-yloxy)acetic acid, 2,5,7,8-tetramethyl-(2R-(4R,8R,12-trimethyltridecyl)chroman-6-yloxy)propionic acid, 2,5,7,8-tetramethyl-(2R-(4R,8R,12-trimethyltridecyl)chroman-6-yloxy)butyric acid, 2,5,8-trimethyl-(2R-(4R,8R,12-trimethyltridecyl)chroman-6-yloxy)acetic acid, 2,7,8-trimethyl-(2R-(4R,8R,12-trimethyltridecyl)chroman-6-yloxy)acetic acid, 2,8-dimethyl-(2R-(4R,8R,12-trimethyltridecyl)chroman-6-yloxy)acetic acid, 2-(N,N-(carboxymethyl)-2(2,5,7,8-tetramethyl-(2R-(4R,8R,12-trimethyltridecyl)chroman-6-yloxy)acetic acid, 2,5,7,8-tetramethyl-(2RS-(4RS,8RS,12-trimethyltridecyl)chroman-6-yloxy)acetic acid, 2,5,7,8-tetramethyl-2R-(2RS,6RS,10-trimethylundecyl)chroman-6-yloxy)acetic acid, 3-(2,5,7,8-tetramethyl-(2R-(4R,8,12-trimethyltridecyl)chroman-6-yloxy)propyl-1-ammonium chloride, 2,5,7,8-tetramethyl-(2R-(4r,8R,12-trimethyltridecyl)chroman-3-ene-6-yloxy)acetic acid, 2-(2,5,7,8-tetramethyl-(2R-(4R,8,12-trimethyltridecyl)chroman-6-yloxy)triethylammonium sulfate, 6-(2,5,7,8-tetramethyl-(2R-(4R,8,12-trimethyltridecyl)chroman)acetic acid, 2,5,7,8,-tetramethyl-(2R-(heptadecyl)chroman-6-yloxy)acetic acid, 2,5,7,8,-tetramethyl-2R-(4,8,-dimethyl-1,3,7 E:Z nonotrien)chroman-6-yloxy)acetic acid, and E,Z,RS,RS-(phytyltrimethylbenzenethiol-6-yloxy)acetic acid.
- 20. The method of claim 18, wherein said method is useful in the treatment of a cell proliferative disease.
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] This patent application claims benefit of provisional application U.S. Ser. No. 60/101,542, filed Sep. 23, 1998, now abandoned.
Provisional Applications (1)
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Number |
Date |
Country |
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60101542 |
Sep 1998 |
US |
Divisions (1)
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Number |
Date |
Country |
Parent |
09404001 |
Sep 1999 |
US |
Child |
10122019 |
Apr 2002 |
US |