Compounds and methods for selective inhibition of dipeptidyl peptidase-IV

• US 7,825,139 B2
• Filed: 05/25/2006
• Issued: 11/02/2010
• Est. Priority Date: 05/25/2005
• Status: Expired due to Fees

• Current Assignee: Forest Laboratories Holdings Limited (Abbvie Incorporated)
• Original Assignee: Forest Laboratories Holdings Limited (Abbvie Incorporated)
• Inventors: Campbell, David Alan, Winn, David T., Betancort, Juan Manuel
• Primary Examiner(s): CHANG, CELIA C
• Application Number:
  US11/420,273
• Publication Number:
  US 20060276410A1
• Time in Patent Office: 1,622 Days
• Field of Search: 546/208, 514/326
• US Class Current: 514/326
• CPC Class Codes: C07F 5/025 Boronic and borinic acid compounds

Abstract

Compounds that selectively inhibit dipeptidyl peptidase-IV over closely related dipeptidyl peptidases are those of Formula (I):

as well as pharmaceutically acceptable salts thereof, cyclic isomers thereof, prodrugs thereof, and solvates thereof, where all the variables are defined herein. These compounds can be used, alone or in combination with other drugs, for the treatment of diabetes and related diseases.

Claims

1. A compound selected from the group consisting of:

(2R)-1-[(3R,4R)-4-amino-1-benzenesulfonyl-piperidine-3-carbonyl]-boroPro-OH,

(2R)-1-[(3R,4R)-4-amino-1-methanesulfonyl-piperidine-3-carbonyl]-boroPro-OH,

(2R)-1-[(3R,4R)-4-amino-1-(4-fluoro-benzenesulfonyl)-piperidine-3-carbonyl]-boroPro-OH,

(2R)-1-[(3R,4R)-4-amino-1-(3-fluoro-benzenesulfonyl)-piperidine-3-carbonyl]-boroPro-OH,

(2R)-1-[(3R,4R)-4-amino-1-(2-fluoro-benzenesulfonyl)-piperidine-3-carbonyl]-boroPro-OH,

(2R)-1-[(3R,4R)-4-amino-1-(2,4-difluoro-benzenesulfonyl)-piperidine-3-carbonyl]-boroPro-OH,

(2R)-1-[(3R,4R)-4-amino-1-(2,4,5-trifluoro-benzenesulfonyl)-piperidine-3-carbonyl]-boroPro-OH,

(2R)-1-[(3R,4R)-4-amino-1-(4-methanesulfonyl-benzenesulfonyl)-piperidine-3-carbonyl]-boroPro-OH,

(2R)-1-[(3R,4R)-4-amino-1-(naphthalene-1-sulfonyl)-piperidine-3-carbonyl]-boroPro-OH,

(2R)-1-[(3R,4R)-4-amino-1-(naphthalene-2-sulfonyl)-piperidine-3-carbonyl]-boroPro-OH,

(2R)-1-[(3R,4R)-4-amino-1-(biphenyl-4-sulfonyl)-piperidine-3-carbonyl]-boroPro-OH,

(2R)-1-[(3R,4R)-4-amino-1-(biphenyl-3-sulfonyl)-piperidine-3-carbonyl]-boroPro-OH, and

(2R)-1-[(3R,4R)-4-amino-1-(propane-2-sulfonyl)-piperidine-3-carbonyl]-boroPro-OH.

2. The compound of claim 1, wherein the compound is (2R)-1-[(3R,4R)-4-amino-1-benzenesulfonyl-piperidine-3-carbonyl]-boroPro-OH.

3. The compound of claim 1, wherein the compound is (2R)-1-[(3R,4R)-4-amino-1-methanesulfonyl-piperidine-3-carbonyl]-boroPro-OH.

4. The compound of claim 1, wherein the compound is (2R)-1-[(3R,4R)-4-amino-1-(4-fluoro-benzenesulfonyl)-piperidine-3-carbonyl]-boroPro-OH.

5. The compound of claim 1, wherein the compound is (2R)-1-[(3R,4R)-4-amino-1-(3-fluoro-benzenesulfonyl)-piperidine-3-carbonyl]-boroPro-OH.

6. The compound of claim 1, wherein the compound is (2R)-1-[(3R,4R)-4-amino-1-(2-fluoro-benzenesulfonyl)-piperidine-3-carbonyl]-boroPro-OH.

7. The compound of claim 1, wherein the compound is (2R)-1-[(3R,4R)-4-amino-1-(2,4-difluoro-benzenesulfonyl)-piperidine-3-carbonyl]-boroPro-OH.

8. The compound of claim 1, wherein the compound is (2R)-1-[(3R,4R)-4-amino-1-(2,4,5-trifluoro-benzenesulfonyl)-piperidine-3-carbonyl]-boroPro-OH.

9. The compound of claim 1, wherein the compound is (2R)-1-[(3R,4R)-4-amino-1-(4-methanesulfonyl-benzenesulfonyl)-piperidine-3-carbonyl]-boroPro-OH.

10. The compound of claim 1, wherein the compound is (2R)-1-[(3R,4R)-4-amino-1-(naphthalene-1-sulfonyl)-piperidine-3-carbonyl]-boroPro-OH.

11. The compound of claim 1, wherein the compound is (2R)-1-[(3R,4R)-4-amino-1-(naphthalene-2-sulfonyl)-piperidine-3-carbonyl]-boroPro-OH.

12. The compound of claim 1, wherein the compound is (2R)-1-[(3R,4R)-4-amino-1-(biphenyl-4-sulfonyl)-piperidine-3-carbonyl]-boroPro-OH.

13. The compound of claim 1, wherein the compound is (2R)-1-[(3R,4R)-4-amino-1-(biphenyl-3-sulfonyl)-piperidine-3-carbonyl]-boroPro-OH.

14. The compound of claim 1, wherein the compound is (2R)-1-[(3R,4R)-4-amino-1-(propane-2-sulfonyl)-piperidine-3-carbonyl]-boroPro-OH.

15. The pharmaceutical composition comprising a compound of claim 1 and a pharmaceutically acceptable carrier.

16. A composition comprising a selective DPP-IV inhibitory effective amount of a compound of claim 1 and a pharmaceutically acceptable carrier.

17. The method of treating hyperglycemia comprising administering to a mammal in need thereof an effective amount of a compound of claim 1.

18. The method of claim 17, wherein the hyperglycemia is in diabetes.