The present invention pertains to an improved chemical synthesis method for Ahp-cyclodepsipeptides which allows straight forward and easy synthesis of tailor-made Ahp-cyclodepsipeptides. The invention further provides Ahp-cyclodepsipeptides for use as HTRA protease inhibitors and their medical use.

The present invention provides cyclic depsipeptides of Formula (1), stereoisomers thereof, and veterinary acceptable salts thereof ##STR00001##
wherein each of R.sup.1, R.sup.2, R.sup.3, R.sup.4, L.sub.1, and L.sub.2, are as defined herein. The present invention also contemplates compositions and methods of treatment as an endoparasiticide with a Formula (1) compound.

The present invention provides cyclic depsipeptides of Formula (1), stereoisomers thereof, and veterinary acceptable salts thereof ##STR00001##
wherein each of R.sup.1, R.sup.2, R.sup.3, R.sup.4, L.sub.1, and L.sub.2, are as defined herein. The present invention also contemplates compositions and methods of treatment as an endoparasiticide with a Formula (1) compound.

Methods of producing a peptide containing an N-substituted amino acid or N-substituted amino acid analog of the present invention include the steps of: preparing an Fmoc-protected amino acid, an Fmoc-protected amino acid analog, or an Fmoc-protected peptide; deprotecting a protecting group which have an Fmoc skeleton of the Fmoc-protected amino acid and such by using a base; and forming an amide bond by adding a new Fmoc-protected amino acid and such; and when the peptide is produced by a solid-phase method, the obtained peptide is cleaved off from the solid phase under conditions of weaker acidity than TFA. Furthermore, at least one side chain of the obtained peptide has a protecting group that is not deprotected under basic conditions and is deprotected under conditions of weaker acidity than TFA.

Methods of producing a peptide containing an N-substituted amino acid or N-substituted amino acid analog of the present invention include the steps of: preparing an Fmoc-protected amino acid, an Fmoc-protected amino acid analog, or an Fmoc-protected peptide; deprotecting a protecting group which have an Fmoc skeleton of the Fmoc-protected amino acid and such by using a base; and forming an amide bond by adding a new Fmoc-protected amino acid and such; and when the peptide is produced by a solid-phase method, the obtained peptide is cleaved off from the solid phase under conditions of weaker acidity than TFA. Furthermore, at least one side chain of the obtained peptide has a protecting group that is not deprotected under basic conditions and is deprotected under conditions of weaker acidity than TFA.

The present invention relates to the use of compounds in the treatment of inflammation, preferably inflammation associated with activation of Toll-like receptors. The invention also relates to the use of compounds to treat pathogen-induced inflammation.

The present invention relates to the use of compounds in the treatment of inflammation, preferably inflammation associated with activation of Toll-like receptors. The invention also relates to the use of compounds to treat pathogen-induced inflammation.

The present invention relates generally to novel depsipeptides, to methods for the preparation of these novel depsipeptides, to pharmaceutical compositions comprising the novel depsipeptides; and to methods of using the novel depsipeptides to treat or inhibit various disorders.

The present invention relates generally to novel depsipeptides, to methods for the preparation of these novel depsipeptides, to pharmaceutical compositions comprising the novel depsipeptides; and to methods of using the novel depsipeptides to treat or inhibit various disorders.

The present invention relates to polypeptides which are covalently bound to non-aromatic molecular scaffolds such that two or more peptide loops are subtended between attachment points to the scaffold. In particular, the invention describes peptides which are high affinity binders of the Eph receptor tyrosine kinase A2 (EphA2). The invention also relates to pharmaceutical compositions comprising said peptide ligands and to the use of said peptide ligands in preventing, suppressing or treating a disease or disorder characterised by overexpression of EphA2 in diseased tissue (such as a tumour).