PYRROLIDINE COMPOUNDS AND METHODS FOR SELECTIVE INHIBITION OF DIPEPTIDYL PEPTIDASE-IV

• US 20070299036A1
• Filed: 08/02/2007
• Published: 12/27/2007
• Est. Priority Date: 11/12/2003
• Status: Active Grant

• Current Assignee: Sino-Med International Alliance Inc.
• Original Assignee: Phenomix Corporation
• Inventors: Winn, David, Campbell, David, Betancort, Juan
• Granted Patent: US 7,906,658 B2
• Time in Patent Office: Days
• US Class Current: 514/64
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: C07F 5/025 Boronic and borinic acid compounds

Abstract

The present invention is directed to a method of treatment of a malcondition that can be regulated or normalized via inhibition of DPP-IV. The method involves administration of an effective amount of a pyrrolidine compound of the invention, such as would be present in a pharmaceutical composition of the invention, to mammals, especially humans, to affect a malcondition that can be regulated or normalized via inhibition of DPP-IV.

Claims

1. A method for inhibiting dipeptidyl peptidase-IV comprising contacting dipeptidyl peptidase-IV with an effective amount of a pyrrolidine compound represented by formula I:

2. The method of claim 1 wherein the dipeptidyl peptidase-IV is within a mammal in need of treatment for a malcondition that can be regulated or normalized via inhibition of dipeptidyl peptidase-IV and the contacting step comprises administering to the mammal a therapeutically effective amount of a compound of formula I.

3. The method of claim 2, wherein the malcondition is impaired glycemic control.

4. The method of claim 2, wherein the malcondition is diabetes.

5. The method of claim 2, further comprising administering a therapeutically effective amount of a second medicament selected from the group consisting of a known second medicament that increases insulin secretion, increases insulin sensitivity, reduces the uptake of sugar from the gastrointestinal track, enhances the effect of endogenous peptides or proteins that affect glycemic control, or provides a replacement for endogenous peptides, proteins that affect glycemic control, or any combination thereof.

6. The method of claim 1, wherein the pyrrolidine compound selectively inhibits dipeptidyl peptidase-IV over at least one other dipeptidyl peptidase.

7. The method of claim 6, wherein the selective inhibition is by greater than 5-fold.

8. The method of claim 7, wherein the pyrrolidine compound selectively inhibits dipeptidyl peptidase-IV over dipeptidyl peptidase-VII, dipeptidyl peptidase-VIII, dipeptidyl peptidase-IX or fibroblast activation protein.

9. The method of claim 7, wherein the pyrrolidine compound selectively inhibits dipeptidyl peptidase-IV over dipeptidyl peptidase-VIII by greater than 10-fold.

10. The method of claim 7, wherein the pyrrolidine compound selectively inhibits dipeptidyl peptidase-IV over dipeptidyl peptidase-VIII and fibroblast activation protein.

11. The method of claim 7, wherein the pyrrolidine compound selectively inhibits dipeptidyl peptidase-IV over dipeptidyl peptidase-VII, dipeptidyl peptidase-VIII, and fibroblast activation protein.