Glycosylated cyclic endomorphin analogs

Abstract

For example, the formula (I): A, which is useful in the treatment of pain 1 -Cyclo[A 2 -A 3 -A 4 -A 5 -A 6 -O-Carb, the formula (II): A 1 -Cyclo[A 5 -A 3 -A 4 -A 2 -A 6 -O-Carb glycosylated cyclic peptides, and pharmaceutically acceptable salts thereof, are described herein. In some embodiments, A 1 is L-Tyr; A 2 is D-Lys, D-Orn, D-Dab, or D-Dpr; A 3 is L-Trp; A 4 is L-Phe; A 5 is an amino acid residue selected from the group consisting of Asp, Glu, iso-Asp, and iso-Glu; A 6 is (a) a hydroxy-substituted amino acid residue (HO-AA), or (b) an oligopeptide containing 2-5 amino acid residues including HO-AA; Carb is a carbohydrate group bonded to the side-chain oxygen of HO-AA by a β-D-glycoside bond, and optionally, the C-terminus of A 6 is amidated, for example, as a primary amide.

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