US 11,787,837 B2 · DCHBS-active esters of PEG compounds and their use

Abstract

The present invention relates to a novel acylating agent, a method for its preparation, and a method of using it for acylating one or more amino groups of an amino acid, a peptide, or a protein. The novel acylating agent may be a compound which comprises a structural element —HN—(CH2)2-(O—((CH2)2)k-O—(CH2)n-CO—, wherein k is an integer in the range of 1-10, and n is an integer in the range of 1-2, being esterified at its —CO-end to the hydroxy group of 3,5-dichloro-2-hydroxy-benzenesulfonic acid (3,5-DC-2-HBSA). This novel acylating agent has an improved stability. Using this agent the acylation process is improved as regards robustness, as well as improving yield and overall production economy. The novel acylating agent is useful for acylating pharmaceutical peptides and proteins such as GLP-1, insulin, pYY, and amylin. The invention also relates to a number of novel GLP-1 precursor peptides and derivatives in which the two N-terminal amino acids have been deleted.

Claims16

Dependent claims

A compound which comprises Chem. 7b:

wherein
n is an integer in the range of 1-2,
—Z1 and —Z2 independently are selected from the group consisting of —Cl, —F, —Br, —NO2, —CN, —SO2X2, —CONH, and —CF3, wherein X2 is selected from the group consisting of —OH, CH3, —CF3, and —N(R1R2),
—Y1 and —Y2 independently are absent or selected from the group consisting of —Cl and —F,
—X is selected from the group consisting of —OH, CH3, —CF3, and —N(R1R2),
wherein R1 and R2 independently are selected from the group consisting of H and C1-C5 alkyl, wherein C1-C5 alkyl may be linear, branched or cyclic and optionally substituted with a hydrophilic moiety;
or a salt thereof.

4 more elements

Dependencies are inferred from the claim text.

DCHBS-active esters of PEG compounds and their use

Life of this patent

DCHBS-active esters of PEG compounds and their use

Life of this patent

Abstract

Claims16