Claims
- 1. A compound having the formula
- 2. The compound of claim 1 wherein R2 is an alkyl or substituted alkyl group.
- 3. The compound of claim 1 wherein R2 is a —CH2CO2H group.
- 4. The compound of claim 1 wherein “- - -” is present.
- 5. The compound of claim 1 wherein R7 is hydrogen.
- 6. The compound of claim 1 wherein R8 is hydrogen.
- 7. The compound of claim 1 wherein R1 is hydrogen.
- 8. The compound of claim 1 wherein W is —S—.
- 9. The compound of claim 1 wherein X is —O—, or —S—.
- 10. The compound of claim 1 wherein X is —O—.
- 11. The compound of claim 1 wherein W is —S—, and X is —O—.
- 12. The compound of claim 1 wherein W is —S—, and X is —S—.
- 13. The compound of claim 1 wherein R5 and R6 together with the aromatic ring form a cycloalkyl ring, or a substituted cyloalkyl ring having from one to four substituent groups independently selected from inorganic radicals selected from halogen, cyano, nitro, hydroxyl, amino, and from organic radicals comprising from one to four carbon atoms independently selected from alkyl, substituted alkyl, acyloxy, alkoxy, substituted alkoxy, acyl, mono-substituted amino, di-substituted amino, carboxy, carboalkoxy, alkylcarboxamide, or dialkylcarboxamide groups.
- 14. The compound of claim 13 wherein the cycloalkyl ring, or substituted cyloalkyl ring together with the aromatic ring comprise a fused ring having the structures
- 15. The compound of claim 13 wherein the cycloalkyl ring, or substituted cyloalkyl ring comprises 1, 2 or 3 heteroatoms or heteroatomic groups that can include O, S, SO, SO2 and N, wherein N can be optionally further substituted with hydrogen, alkyl or substituted alkyl groups comprising one to ten carbon atoms.
- 16. The compound of claim 1 wherein Ar1 has the structure
- 17. The compound of claim 1 wherein R5 and R6 together with the aromatic ring form a cycloalkenyl ring, or a substituted cyloalkenyl ring having from one to four substituent groups independently selected from inorganic radicals selected from halogen, cyano, nitro, hydroxyl, amino, and from organic radicals comprising from one to four carbon atoms independently selected from alkyl, substituted alkyl, acyloxy, alkoxy, substituted alkoxy, acyl, mono-substituted amino, di-substituted amino, carboxy, carboalkoxy, alkylcarboxamide, or dialkylcarboxamide groups.
- 18. The compound of claim 1 wherein Ar2 is an aryl ring optionally substituted with one, two, or three substituent groups independently selected from inorganic radicals selected from halogen, cyano, nitro, hydroxyl, amino, and from organic radicals comprising from one to four carbon atoms independently selected from alkyl, substituted alkyl, haloalkyl, haloalkoxy, acyloxy, alkoxy, substituted alkoxy, acyl, mono-substituted amino, di-substituted amino, carboxy, carboalkoxy, alkylcarboxamide, or dialkylcarboxamide groups.
- 19. The compound of claim 1 wherein Ar2 has the structure
- 20. The compound of claim 1 wherein Ar2 has the structure
- 21. The compound of claim 1 wherein Ar2 has the structure
- 22. The compound of claim 1 wherein Ar2 is a heteroaryl ring optionally substituted with one, two, or three substituent groups independently selected from inorganic radicals selected from halogen, cyano, nitro, hydroxyl, amino, and from organic radicals comprising from one to four carbon atoms independently selected from alkyl, substituted alkyl, acyloxy, alkoxy, substituted alkoxy, acyl, mono-substituted amino, di-substituted amino, carboxy, carboalkoxy, alkylcarboxamide, or dialkylcarboxamide radicals.
- 23. The compound of claim 1 wherein Ar2 has the structure
- 24. The compound of claim 23 wherein Ar2 comprises a heteroaryl ring having the structure
- 25. The compound of claim 23 wherein Ar2 comprises a heteroaryl ring having the structure
- 26. The compound of claim 1 that when applied at a concentration of about 10 uM to a human tumor cell line culture for leukemia, lung cancer, colon cancer, CNS cancer, melanoma, ovarian cancer, renal cancer, prostate cancer, breast cancer, or pancreatic cancer is effective to inhibit cell growth of the tumor cells by 50% or more.
- 27. A compound of claim 1 that is effective, when applied at a concentration of about 10 uM, to inhibit by at least 25% the adipocite differentiation induced by rosiglitazone which is applied at a concentration of 0.1 uM.
- 28. A compound having the formula
- 29. The compound of claim 28 wherein “- - -” is present.
- 30. The compound of claim 28 wherein R1 is hydrogen.
- 31. The compound of claim 28 wherein Ar2 has the formula
- 32. A compound present as:
{5-[4-Methoxy-3-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-naphthalen -2-yl)-benzylidene]-4-oxo-2-thioxo-thiazolidin-3-yl}-acetic acid; {5-[4-Trifluoromethoxy-3-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-naphthalen -2-yl)-benzylidene]-4-oxo-2-thioxo-thiazolidin-3-yl}-acetic acid; {5-[6-Methoxy-5-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-naphthalen -2-yl)-pyridin-3-yl methylene]-4-oxo-2-thioxo-thiazolidin-3-yl}-acetic acid; 3-Ethyl-{5-[4-Trifluoromethoxy-3-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-naphthalen-2-yl)-benzylidene]-2-thioxo-thiazolidin-4-one; 3-Methyl-{5-[4-Trifluoromethoxy-3-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-naphthalen-2-yl)-benzylidene]-2-thioxo-thiazolidin-4-one; 5-[4-Methoxy-3-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-naphthalen -2-yl)-benzylidene]-3-(2-pyridin-2-yl-ethyl)-thiazolidine-2,4-dione; {5-[6-(3-Dimethylamino-5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-naphthalen -2-yl)-naphthalen-2-yl methylene]-4-oxo-2-thioxo-thiazolidin-3-yl}-acetic acid; {5-[5-Phenyl-3-methoxy-2-(3-methoxy-5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-naphthalen-2-yl)-benzylidene]-4-oxo-2-thioxo-thiazolidin-3-yl}-acetic acid; {5-[3-Methoxy-2-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-naphthalen -2-yl)-benzylidene]-4-oxo-2-thioxo-thiazolidin-3-yl}-acetic acid; {5-[4-Dimethylamino-3-(3-dimethylamino-5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-naphthalen-2-yl)-benzylidene]4-oxo-2-thioxo-thiazolidin-3-yl}-acetic acid; or {5-[(3-t-Butyl-4-methoxyphenyl)-6-ethoxy-benzylidene]-4-oxo-2-thioxo-thiazolidin-3-yl}-acetic acid; or a pharmaceutically acceptable salt thereof.
- 33. A pharmaceutical composition for administration in mammals comprising one or more pharmaceutically acceptable carriers and one or more compounds of claim 1 in an amount effective for treating obesity, modulating lipid metabolism, carbohydrate metabolism, lipid and carbohydrate metabolism, or adipocyte differentiation.
- 34. A method of modulating lipid metabolism, carbohydrate metabolism, lipid and carbohydrate metabolism, or adipocyte differentiation comprising administering to a mammal diagnosed as needing such modulation the pharmaceutical composition of claim 33.
- 35. A method of treating hypercholesterimia comprising administering to a mammal diagnosed as needing such treatment the pharmaceutical composition of claim 33.
- 36. The method of claim 35, wherein the compound is applied in an amount effective to decrease serum cholesterol levels by at least about 5%.
- 37. A method of treating dyslipidemia comprising administering to a mammal diagnosed as needing such treatment the pharmaceutical composition of claim 33 in an amount effective to decrease triglyceride levels.
- 38. The method of claim 37, wherein the compound is applied in an amount effective to decrease triglyeride levels by at least about by at least 5%.
- 39. A method of treating Type 2 Diabetes comprising administering to a mammal diagnosed as needing such treatment the pharmaceutical composition of claim 33 in an amount effective to decrease blood sugar levels of the mammal.
- 40. The method of claim 39, wherein the compound is applied in an amount effective to to decrease blood sugar levels by at least about by at least 5%.
- 41. The method of claim 34 wherein the mammal is a human.
- 42. A pharmaceutical composition for treating a disease of uncontrolled cellular proliferation in mammals comprising one or more pharmaceutically acceptable carriers and one or more compounds of claim 1.
- 43. A method of treatment for a disease of uncontrolled cellular proliferation comprising administering to a mammal diagnosed as having a disease of uncontrolled cellular proliferation the pharmaceutical composition of claim 42 in an amount that is effective to treat the disease of uncontrolled cellular proliferation.
- 44. The method of claim 43, wherein the disease of uncontrolled cellular proliferation is cancer.
- 45. The method of claim 43, wherein the disease of uncontrolled cellular proliferation is carcinoma, lymphoma, leukemia, or sarcoma.
- 46. The method of claim 43, wherein the disease of uncontrolled cellular proliferation is Hodgkin's Disease, meyloid leukemia, polycystic kidney disease, bladder cancer, brain cancer, head and neck cancer, kidney cancer, lung cancer, myeloma, neuroblastoma/glioblastoma, ovarian cancer, pancreatic cancer, prostate cancer, skin cancer, liver cancer, melanoma, colon cancer, cervical carcinoma, breast cancer, epithelial cancer, and leukemia.
- 47. A method of claim 43, wherein the disease of uncontrolled cellular proliferation is breast cancer.
- 48. The method of claim 43 wherein the mammal is a human.
- 49. A method of treating obesity in mammals comprising administering to a mammal diagnosed as needing such treatment the pharmaceutical composition of claim 33, wherein the pharmaceutical composition is administered in an amount effective to decrease or prevent weight gain in diabetic db/db mice or ob/ob mice.
- 50. The method of claim 49, wherein the compound is applied in an amount effective to decrease or prevent weight gain by at least about by at least 5%.
RELATED APPLICATIONS
[0001] This application claims priority to the U.S. Provisional Application Serial No. 60/334,794, filed Nov. 15, 2001, the disclosure of which application is hereby incorporated in its entirety by this reference. This application claims priority to U.S. Provisional Application No. 60/362,702, filed Mar. 8, 2002, the disclosure and description of which is hereby incorporated by reference in its entirety into the current application for all purposes, and particularly for its disclosures of potential structures for Ar1 groups having amide groups incorporated therein, and methods for the precursors employed for the synthesis of the Ar1 groups of the current invention. This application also claims priority to U.S. Provisional Application No. 60/362,732, filed Mar. 8, 2002. The disclosure of U.S. Provisional Application No. 60/362,732 is hereby incorporated by reference in its entirety into the current application for all purposes, and particularly for its disclosures of potential structures for bicyclic heterocyclic Ar1 groups, and methods for the precursors employed for the synthesis of the bicyclic heterocyclic Ar1 groups of the current invention.
Provisional Applications (3)
|
Number |
Date |
Country |
|
60334794 |
Nov 2001 |
US |
|
60362702 |
Mar 2002 |
US |
|
60362732 |
Mar 2002 |
US |