Aktiebolaget Hassle

Ferring Pharmaceuticals

David M Jones

Michael Szelke

Allan Hallett

Peptides wherein an amide bond is replaced by nonhydrolyzable isosteric linkage are disclosed as thrombogenic inhibitors.

Enzyme inhibition

Renin-inhibiting analogues of formula ##STR1## where X and W are terminal groups optionally with further amino acyl residues; D, E, B and Z (of which any one or except with `reduced` analogues any two may be absent) are aromatic, lipophilic or in the case of E aromatic lipophilic or basic amino acid or amino acid analogue residues; and A is an analogue of a lipophilic or aromatic dipeptide residue wherein the peptide link is replaced by a one- to four-atom carbon or carbon-nitrogen link which as such or in hydrated form is an unhydrolysable tetrahedral analogue of the transition state ##STR2## of peptide bond hydrolysis.

Renin inhibitors and treatments using them

Renin inhibitory polypeptide analogues derived from the natural N-terminal substrate sequence by replacing the amino acid at position 10 with statine or a residue related to it.

Enzyme inhibitors

Preparation of renin inhibitors based on the structure of natural renin substrate at residues 6 to 13 from the amino terminal thereof, the inhibitors being polypeptide analogues having in particular an isosteric non-peptide link corresponding to the 10, 11 peptide link of the substrate, and preparation of dipeptide analogues.

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Hayes, United Kingdom

David M Jones