THERAPEUTIC AND DELIVERY METHODS OF PROSTAGLANDIN EP4 AGONISTS

Abstract

A compound comprising a prodrug of a prostaglandin EP4 agonist, wherein said prodrug is an ester, ether, or amide of an amino acid is disclosed herein.

Description

Claims

1. A compound comprising a prodrug of a prostaglandin EP4 agonist, wherein said prodrug is an ester, ether, or amide of an amino acid.

2. The compound of claim 2 wherein said prostaglandin EP4 agonist is a compound selected from the group consisting of

3. The compound of claim 3 wherein A is —(CH2)6—, cis —CH2CH═CH—(CH2)3—, or —CH2C≡C—(CH2)3—, wherein 1 or 2 carbon atoms may be substituted with S or O; and E is C1-6 alkyl, R2, or —Y—R2 wherein Y is CH2, S, or O, and R2 is aryl or heteroaryl.

4. The compound of claim 4 wherein R2 is phenyl, naphthyl, biphenyl, thienyl, or benzothienyl having from 0 to 2 substituents selected from the group consisting of F, Cl, Br, methyl, methoxy, and CF3.

5. The compound of claim 5 wherein R2 is CH2-naphthyl, CH2-biphenyl, CH2-(2-thienyl), CH2-(3-thienyl), naphthyl, biphenyl, 2-thienyl, 3-thienyl, CH2-(2-(3-chlorobenzothienyl)), CH2-(3-benzothienyl), 2-(3-chlorobenzothienyl), or 3-benzothienyl.

6. The compound of claim 5 wherein the prostaglandin EP4 agonist comprises

7. The compound of claim 7 wherein the prostaglandin EP4 agonist comprises

8. The compound of claim 1, which is a prodrug of

9. The compound of claim 1, which is a prodrug of

10. The compound of claim 1, wherein the amino acid is a natural amino acid.

11. The compound of claim 1, wherein the amino acid is an unnatural amino acid.

12. The compound of claim 1, wherein the prodrug is a C1 amino acid ester.