Pyrrolidine compounds and methods for selective inhibition of dipeptidyl peptidase-IV
View Patent ↗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.
1. A method for treating a malcondition characterized by impaired glycemic control in a human wherein the malcondition is selected from the group consisting of Type 1 diabetes, Type 2 diabetes, gestational diabetes, MODY, impaired glucose tolerance, impaired fasting glucose, hyperglycemia, impaired glucose metabolism, insulin resistance and obesity, comprising administering to a human in need thereof an effective amount of a pharmaceutical composition comprising a pharmaceutically acceptable carrier and a compound of formula (I):
or a pharmaceutically acceptable salt thereof, or hydrate thereof; wherein R 2 and R 3 independently or together are —OH, —O − M + wherein M + is a cation, a hydroxyl bearing a boronic acid protecting group, or a group capable of being hydrolyzed to a hydroxyl group in an aqueous solution at physiological pH or in biological fluids.
2. The method of claim 1 , wherein the compound of formula (I) is:
or a pharmaceutically acceptable salt thereof.
3. The method of claim 2 , wherein the malcondition is diabetes mellitus.
4. The method of claim 2 , wherein the malcondition is type 2 diabetes.
5. The method of claim 2 , wherein the pharmaceutical composition comprises about 10 mg to about 1000 mg of the compound of formula (I) or a pharmaceutically acceptable salt thereof.
6. The method of claim 2 , wherein the pharmaceutical composition comprises about 50 mg to about 750 mg of the compound of formula (I) or a pharmaceutically acceptable salt thereof.
7. The method of claim 2 , wherein the pharmaceutical composition also comprises a therapeutically effective amount of metformin.
8. The method of claim 1 , wherein the compound of formula (I) is a selective inhibitor of DPP-IV.
9. The method of claim 2 , wherein the compound of formula (I) is a selective inhibitor of DPP-IV.