Claims
- 1. A compound of the formula I:
- 2. The compound of claim 1, wherein R12 is a C1-C20 straight or branched chain alkyl group.
- 3. The compound of claim 2, wherein said alkyl group is selected from the group consisting of methyl, ethyl, isopropyl, n-butyl, s-butyl, t-butyl, 3-methyl-n-butyl, n-amyl, isoamyl, n-hexyl, n-octyl and n-decyl.
- 4. The compound of claim 3 wherein said alkyl group is methyl.
- 5. The compound of claim 3 wherein said alkyl group is 3-methyl-n-butyl.
- 6. A compound according to claim 1, wherein said compound has the following formula II:
- 7. The compound of claim 1 wherein A is
- 8. The compound of claim 7 wherein R1′ to R5′ are H.
- 9. The compound of claim 7 wherein R1′″ to R7′″ are H.
- 10. The compound of claim 6 wherein A1 and A2 are independently
- 11. The compound of claim 10 wherein R1′ to R5′ are H.
- 12. The compound of claim 10 wherein R1′″ to R7′″ are H.
- 13. The compound of claim 1 selected from the group consisting of:
(f) 3-(2-carboxyindol-3-yl)-2,5-dihydroxy-6-(2-methylindol-3-yl)-1,4-quinone; (h) 2,5-dihydroxy-6-[2-(3-methyl-n-butyl)indol-3-yl]-3-(2-phenylindol-3-yl)-1,4-quinone; (i) 2,5-dihydroxy-6-(2-methylindol-3-yl)-3-(2-phenylindol-3-yl)-1,4-quinone; (j) 6-(2-n-butylindol-3-yl)-3-(2-carboxyindol-3-yl)-2,5-dihydroxy-1,4-quinone; (l) 3-(2-carboxyindol-3-yl)-2,5-dihydroxy-6-[2-(3-methyl-n-butyl)indol-3-yl]-1,4-quinone; (m) 3-(2-carboxyindol-3-yl)-2,5-dihydroxy-6-(2-phenylindol-3-yl)-1,4-quinone; (n) 3-(2-n-butylindol-3-yl)-6-(2-carboxy-5-chloroindol-3-yl)-2,5-dihydroxy-1,4-quinone; and (q) 3-(2-carboxy-5-chloroindol-3-yl)-2,5-dihydroxy-6-(2-methyl-5-methoxyindol-3-yl)-1,4-quinone; or a pharmaceutically acceptable salt thereof.
- 14. The compound of claim 6 selected from the group consisting of:
(g) 2,5-dihydroxy-3,6-di-(2-phenylindol-3-yl)-1,4-quinone; and (r) 2,5-dihydroxy-3,6-di-(2-naphthylindol-3-yl)-1,4-quinone; or a pharmaceutically acceptable salt thereof.
- 15. A compound selected from the group consisting of:
(o) 2,5-dihydroxy-3,6-di-(5-methoxy-2-methylindol-3-yl)-1,4-quinone; (p) 3,6-di-(5-chloro-2-methylindol-3-yl)-2,5-dihydroxy-1,4-quinone; (s) 3-[2-(N-butylcarboxamido)-indol-3-yl)]-6-(n-butylindol-3-yl)-2,5-dihydroxy-1,4-quinone; (u) 2,5-dihydroxy-3-(1,2-dimethylindol-3-yl)-6-(2-methylindol-3-yl)-1,4-quinone; (v) 3-(1-benzyl-2-methylindol-3-yl)-2,5-dihydroxy-6-(2-methylindol-3-yl)-1,4-quinone; and (w) 2-hydroxy-5-methoxy 3,6 di[2(3 methyl n butyl)indol 3 yl]1,4 -quinone; or a pharmaceutically acceptable salt thereof.
- 16. A pharmaceutical composition suitable for administration to humans which comprises a compound of the formula I:
- 17. The composition of claim 16, wherein R12 is a C1-C20 straight or branched chain alkyl group.
- 18. The composition of claim 17, wherein said alkyl group is selected from the group consisting of methyl, ethyl, isopropyl, n-butyl, s-butyl, t-butyl, 3-methyl-n-butyl, n-amyl, isoamyl, n-hexyl, n-octyl and n-decyl.
- 19. The composition of claim 18, wherein said alkyl group is methyl.
- 20. The composition of claim 18, wherein said alkyl group is 3-methyl-n-butyl.
- 21. The composition of claim 16 wherein A is
- 22. The pharmaceutical composition of claim 16 wherein said compound has the formula II:
- 23. The composition of claim 22, wherein A1, and A2 are each independently
- 24. A pharmaceutical composition suitable for administration to humans, which comprises a compound of claim 13, 14 or 15 and a pharmaceutically acceptable carrier or excipient.
- 25. A method of ameliorating the symptoms of a cell proliferative disorder, which comprises administering a therapeutically effective amount of compound of the following formulae:
- 26. A method of ameliorating the symptoms of a cell proliferative disorder which comprises administering a therapeutically effective amount of the pharmaceutical composition of claim 16.
- 27. The method of claim 25 or 26, wherein said cell proliferative disorder involves an interaction between GRB-2 and tyrosine kinase.
- 28. The method of claim 25 or 26, wherein the cell proliferative disorder occurs in a mammal and the compound contacts the cell within a mammal so that the symptoms of the cell proliferative disorder are ameliorated.
- 29. The method of claim 25 or 26, wherein the cell proliferative disorder is a solid tumor.
- 30. The method of claim 25 or 26, wherein the cell proliferative disorder is a BCR-ABL-associated cancer, a glioma, a glioblastoma, a melanoma, an ovarian cancer, a breast cancer, or a prostate cancer.
- 31. A method of treating diabetes in an animal, which comprises administering to said animal a therapeutically effective amount of compound of the following formulae:
- 32. A method of treating diabetes in an animal, which comprises administering to said animal a therapeutically effective amount of a compound selected from the group consisting of:
(a) 2,5-dihydroxy-3,6-di-(2-methylindol-3-yl)-1,4-quinone; (b) 2,5-dihydroxy-3,6-di-[2-(3-methyl-n-butyl)indol-3-yl]-1,4-quinone; (c) 2,5-dihydroxy-3,6-di-(3-ethylindol-3-yl)-1,4-quinone; (d) 2,5-dihydroxy-3,6-di-(2-n-butylindol-3-yl)-1,4-quinone; (e) 2,5-diacetoxy-3,6-di-[2-(3-methyl-n-butyl)indol-3-yl]-1,4-quinone; (f) 3-(2-carboxyindol-3-yl)-2,5-dihydroxy-6-(2-methylindol-3-yl)-1,4-quinone; (g) 2,5-dihydroxy-3,6-di-(2-phenylindol-3-yl)-1,4-quinone; (h) 2,5-dihydroxy-6-[2-(3-methyl-n-butyl)indol-3-yl]-3-(2-phenylindol-3-yl)-1,4-quinone; (i) 2,5-dihydroxy-6-(2-methylindol-3-yl)-3-(2-phenylindol-3-yl)-1,4-quinone; (j) 6-(2-n-butylindol-3-yl)-3-(2-carboxyindol-3-yl)-2,5-dihydroxy-1,4-quinone; (k) 2,5-dihydroxy-3,6-di-[2-(2-phenylethyl)indol-3-yl]-1,4-quinone; (l) 3-(2-carboxyindol-3-yl)-2,5-dihydroxy-6-[2-(3-methyl-n-butyl)indol-3-yl]-1,4-quinone; (m) 3-(2-carboxyindol-3-yl)-2,5-dihydroxy-6-(2-phenylindol-3-yl)-1,4-quinone; (n) 3-(2-n-butylindol-3-yl)-6-(2-carboxy-5-chloroindol-3-yl)-2,5-dihydroxy-1,4-quinone; (o) 2,5-dihydroxy-3,6-di-(5-methoxy-2-methylindol-3-yl)-1,4-quinone; (p) 3,6-di-(5-chloro-2-methylindol-3-yl)-2,5-dihydroxy-1,4-quinone; (q) 3-(2-carboxy-5-chloroindol-3-yl)-2,5-dihydroxy-6-(2-methyl-5-methoxyindol-3-yl)-1,4-quinone; (r) 2,5-dihydroxy-3,6-di-(2-naphthylindol-3-yl)-1,4-quinone; (s) 3-[2-(N-butylcarboxamido)-indol-3-yl)]-6-(n-butylindol-3-yl)-2,5-dihydroxy-1,4-quinone; (t) 2,5-dimethoxy-3,6-di-[2-(3-methyl-n-butyl)indol-3-yl]-1,4-quinone; (u) 2,5-dihydroxy-3-(1,2-dimethylindol-3-yl)-6-(2-methylindol-3-yl)-1,4-quinone; (v) 3-(1-benzyl-2-methylindol-3-yl)-2,5-dihydroxy-6-(2-methylindol-3-yl)-1,4-quinone; (w) 2-hydroxy-5-methoxy-3,6-di-[2-(3-methyl-n-butyl)-indol-3-yl]-1,4-quinone, and pharmaceutically acceptable salts thereof.
- 33. The method of claim 31 or 32 wherein said compound stimulates insulin receptor tyrosine kinase activity in said animal.
- 34. The method of claim 31 or 32, wherein said compound mimics the action of insulin in the body of said animal.
- 35. A method of ameliorating symptoms of insulin deficiency which comprises administering an effective amount of a compound of claim 1 or a pharmaceutically acceptable salt thereof.
- 36. The method of claim 35, wherein the insulin deficiency occurs in a mammal.
- 37. The method of claim 35, wherein the insulin deficiency results from insulin-dependent diabetes mellitus, non-insulin-dependent diabetes mellitus, insulin resistance, or insulin allergy.
Parent Case Info
[0001] This application is a continuation-in-part of U.S. patent application Ser. No. 09/072,861, filed May 5, 1998, which is currently pending, which is a divisional of U.S. patent application Ser. No. 08/964,791, filed Nov. 5, 1997, now U.S. Pat. No. 5,786,488. The present application also claims priority to U.S. provisional application serial No. 60/030,604, filed Nov. 13, 1996, and U.S. provisional application serial No. 60/042/989, filed Apr. 14, 1997. The present application also claims priority to U.S. patent application serial No. 09/090,737, filed Jun. 4, 1998, which is currently pending, which is continuation of application Ser. No. 08/658,337, filed Jun. 5, 1996, now U.S. Pat. No. 5,780,496, which is a continuation-in-part of U.S. Ser. No. 08/476,136, filed Jun. 7, 1995, abandoned. The disclosures of the above-mentioned applications and patents are each hereby incorporated by reference in their entireties.
Provisional Applications (2)
|
Number |
Date |
Country |
|
60030604 |
Nov 1996 |
US |
|
60042989 |
Apr 1997 |
US |
Divisions (2)
|
Number |
Date |
Country |
Parent |
09405244 |
Sep 1999 |
US |
Child |
09564777 |
May 2000 |
US |
Parent |
08964791 |
Nov 1997 |
US |
Child |
09072861 |
May 1998 |
US |
Continuations (1)
|
Number |
Date |
Country |
Parent |
09072861 |
May 1998 |
US |
Child |
09405244 |
Sep 1999 |
US |