US 2006/0154325 A1 · Synthesis of epoxide based inhibitors of cysteine proteases

Abstract

Epoxide based cysteine protease inhibitors containing peptide derivatives and methods for synthesizing them in sold phase are disclosed. Preferably, an epoxy succinyl “warhead” (for binding to the enzyme) is prepared, having two amino acid residues or residue-like structures on either side. Natural and non-natural amino acids may be used. The present process may be carried out entirely on a solid support, with the proviso that a dipeptide like group is prepared prior to coupling to one side of the supported complex. The method lends itself to more efficient inhibitor synthesis, and may be employed with mixtures of peptide compounds, and various modifications of epoxides to create diverse libraries of inhibitors.

Claims23

Dependent claims

A method for synthesizing an epoxide peptide derivative, comprising:

(a) immobilizing a first peptide derivative to a solid support, whereby the first peptide derivative has a free amino group bound to a protective group;
(b) deprotecting the amino group of the immobilized compound of step (a);
(c) coupling the compound of step (b) to an diester epoxide to form an amide bond with the compound of step (b) to obtain an immobilized ester epoxide—first peptide derivative;
(d) converting the immobilized ester epoxide of step (c) to a free acid and coupling a second peptide derivative to the free acid on the support;
and
(e) releasing the compound of step (d) from the solid support to yield an epoxide having two peptide derivatives attached thereto.

3 more elements

Dependencies are inferred from the claim text.

Synthesis of epoxide based inhibitors of cysteine proteases

Life of this patent

Synthesis of epoxide based inhibitors of cysteine proteases

Life of this patent

Abstract

Claims23