Method of treating defective glucose metabolism using synthetic insulin substances

• US 5,652,221 A
• Filed: 11/07/1994
• Issued: 07/29/1997
• Est. Priority Date: 11/07/1994
• Status: Expired due to Fees

• Current Assignee: University of Virginia Patent Foundation (University of Virginia)
• Original Assignee: University of Virginia Patent Foundation (University of Virginia)
• Inventors: Price, John, Picariello, Thomas, Huang, Laura, Larner, Joseph
• Primary Examiner(s): Kunz, Gary L.
• Assistant Examiner(s): Fonda, Kathleen Kahler
• Application Number:
  US08/335,015
• Time in Patent Office: 995 Days
• Field of Search: 536/17.2, 514/25, 514/35, 514/866, 514/62
• US Class Current: 514/35
• CPC Class Codes: A61P 3/08 for glucose homeostasis pancreatic hormones A61P5/48
• CPC Class Codes: C07H 15/207 Cyclohexane rings not substituted by nitrogen atoms, e.g. kasugamycins
• CPC Class Codes: C07H 17/04 Heterocyclic radicals containing only oxygen as ring hetero atoms

Abstract

A synthetic insulin mimetic compound is disclosed. Small synthetic amines of disaccharides, such as 2-deoxy-2-amino-galactopyranosyl pinitol are shown to mimic the action of insulin and to modulate its action.

Claims

1. A method for the treatment of defective glucose metabolism disorders selected from the group consisting of impaired glucose tolerance, elevated blood glucose associated with Type II diabetes, and insulin resistance, comprising administering to a person in need of such treatment an effective amount of a compound consisting of a 2-amino, D-hexosamine and an inositol, joined by a beta linkage.

2. The method of claim 1 wherein the inositol is selected from the group consisting of myo-inositol and chiro-inositol.

3. The method of claim 1 wherein the inositol is D-pinitol and the linkage to the hexosamine is 1,4'"'"'.

4. The method of claim 3 wherein the hexosamine is selected from the group consisting of D-glucosamine and D-galactosamine.

5. The method of claim 4 wherein the hexosamine is D-galactosamine.

6. The method of claim 2 or 5 wherein at least one of the hydroxyl groups is replaced by a substituent selected from the group consisting of phosphate, C₁ -C₆ alkoxy, C₃ -C₆ cycloalkoxy, C_3-6 ester, C₆ aryloxy, and C₇ -C₈ arylalkoxy.

7. The method of claim 6 wherein at least one of the hydroxyl groups is replaced by a substituent selected from the group consisting of methoxy, ethoxy, and propoxy.

8. The method of claim 5 wherein a substituent selected from the group consisting of phosphate, C₁ -C₆ alkoxy, C₃ -C₆ cycloalkoxy, C_3-6 ester, C₆ aryloxy, and C₇ -C₈ arylalkoxy replaces at least one of the hydroxyls at position 1'"'"', 2'"'"' or 6'"'"' of the inositol ring.

9. The method of claim 2 or 5 wherein at least one of the hydroxyl groups is replaced by a methoxy group or a phosphate group.

10. The method of claim 2 wherein the inositol is chiroinositol and the linkage to the hexosamine is 1,4'"'"'.

11. The method of claim 10 wherein the hexosamine is selected from the group consisting of D-glucosamine and D-galactosamine.

12. The method of claim 11 wherein the hexosamine is D-galactosamine.

13. The method of claim 2 or 12 wherein at least one of the hydroxyl groups is replaced by a substituent selected from the group consisting of phosphate, C₁ -C₆ alkoxy, C₃ -C₆ cycloalkoxy, C_3-6 ester, C₆ aryloxy, and C₇ -C₈ arylalkoxy.

14. The method of claim 12 wherein at least one of the hydroxyl groups is replaced by a substituent selected from the group consisting of methoxy, ethoxy, and propoxy.

15. The method of claim 11 wherein a substituent selected from the group consisting of phosphate, C₁ -C₆ alkoxy, C₃ -C₆ cycloalkoxy, C_3-6 ester, C₆ aryloxy, and C₇ -C₈ arylalkoxy replaces at least one of the hydroxyls at position 1'"'"', 2'"'"', 3'"'"' or 6'"'"' of the inositol ring.

16. The method of claim 2 or 11 wherein at least one of the hydroxyl groups is replaced by a substituent selected from the group consisting of a methoxy group, an amine, and a phosphate group.

17. 4'"'"'-O-(2-deoxy-2-amino-β

-galactopyranosyl)-D-pinitol.