US 5,686,564 A · Peptide derivatives corresponding to the carboxy terminal sequence of hirudin

Abstract

Novel compounds of the formula I ##STR1## in which R.sup.1 and R.sup.2 are hydrogen, C.sub.1 -C.sub.4 alkyl or are linked to form C.sub.3 -C.sub.7 cycloalkyl and R.sup.3, R.sup.4 and R.sup.5 are the same or different and are hydrogen, C.sub.1 -C.sub.4 alkyl, hydroxy, OR.sup.6, SR.sup.6, halogen, NR.sup.7 R.sup.8, NO.sub.2, CN, CONR.sup.7 R.sup.8 or CO.sub.2 R.sup.9 wherein R.sup.6 is C.sub.1 -C.sub.4 alkyl or C.sub.7 -C.sub.10 aralkyl and R.sup.7, R.sup.8 and R.sup.9 are the same or different and are hydrogen, C.sub.1 -C.sub.4 alkyl or C.sub.7 -C.sub.10 aralkyl or R.sup.7 and R.sup.8 together with the nitrogen atom to which they are bound form 5 or 6 membered azacycloalkyl or oxazacycloalkyl; Arg is arginine NH--CH(CH.sub.2 CH.sub.2 CH.sub.2 NH--C(.dbd.NH)--NH.sub.2)--CO!; X is methine CH or nitrogen; n is an integer from 0 to 7; L is a peptide linker, and H is the carboxy terminal end of hirudin, and salts thereof, are provided. The novel compounds are useful for the medical treatment or prevention of thrombosis or diseases caused by thrombosis or can be used for the determination of thrombin in blood as diagnostic reagents.

Claims18

Dependent claims

A compound of the formula I ##STR10## in which R.sub.1 and R.sub.2 are each C.sub.1 -C.sub.4 alkyl, R.sub.3, R.sub.4 and R.sub.5 are each hydrogen;

Arg is arginine, X is selected from the group consisting of methine CH or nitrogen, n is an integer from 0 to 7;
L is a peptide linker comprising 3 to 6 amino acids selected from the group consisting of a C.sub.2 -C.sub.12 -.omega.-amino carboxylic acid, alanine, serine, threonine, glutamine, asparagine, phenylglycine or phenylalanine, and H is the carboxy terminal end of hirudin starting with amino acid 55 and ending at the ultimate or penultimate amino acid of hirudin, a desulphated variant of such a hirudin comprising a tyrosine sulphate residue, a variant of such a hirudin in which the tyrosine sulphate residue is replaced by a tyrosine phosphate residue, or a derivative thereof in which 1-3 amino acids are replaced by other amino acids, which derivatives retain the binding affinity to thrombin, wherein the backbone chain (II) defined by the formula ##STR11## comprises about 18 to about 28, in particular about 22 to about 26, atoms and pharmaceutically acceptable salts thereof.

Dependencies are inferred from the claim text.

Peptide derivatives corresponding to the carboxy terminal sequence of hirudin

Life of this patent

Peptide derivatives corresponding to the carboxy terminal sequence of hirudin

Life of this patent

Abstract

Claims18