Eli Lilly and Company
Fatty acid modified urocortin-2 analogs for the treatment of diabetes and chronic kidney disease

Abstract:

The present invention provides a compound or a pharmaceutically acceptable salt of the Formula: X.sub.1IVX.sub.2SLDVPIGLLQILX.sub.3EQEKQEKEKQQAK*TNAX.sub.4ILAQV-NH.sub.2 wherein the X.sub.1 denotes that the I residue is modified by either acetylation or methylation at the N-terminus; wherein X.sub.2 is L or T; wherein X.sub.3 is L or I; wherein X.sub.4 is Q or E; and wherein a modified K residue ("K*") at position 29 is modified through conjugation to the epsilon-amino group of the K-side chain with a group of the formula --X.sub.5--X.sub.6, wherein X.sub.5 is selected from the group consisting of one to four amino acids; one to four ([2-(2-Amino-ethoxy)-ethoxy]-acetyl) moieties; and combinations of one to four amino acids and one to four ([2-(2-Amino-ethoxy)-ethoxy]-acetyl) moieties; and X.sub.6 is a C.sub.14-C.sub.24 fatty acid. In some embodiments, the group of the formula --X.sub.5--X.sub.6 is ([2-(2-Amino-ethoxy)-ethoxy]-acetyl).sub.2-(.gamma.E).sub.2-CO--(CH.sub.2- ).sub.x--CO.sub.2H where x is 16 or 18.