Enkephalin analogues
OwnerDerek Hudson, Robert Sharpe +1inventors
InventorsDerek Hudson, Robert Sharpe, Michael Szelke
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Abstract
Compounds corresponding in structure to enkephalin or polypeptide analogues thereof, wherein one or more peptide links of the enkephalin or analogue is represented by a group or groups the same or different selected from dimethylene, hydroxydimethylene, methylene-imino and ketomethylene groups and/or wherein adjacent peptide bond nitrogen atoms are linked by a carbonyl or thiocarbonyl group.
Claims21
Compounds of the general formula
- R-Tyr-X-Gly-B-Y-Z
- where (a)
- --X is Gly, aza-Gly, aza-Ala or any D-amino acid residue
- --B is Phe, N-substituted (particularly N-methyl) -Phe or dehydro-Phe all optionally substituted in the ring, or alternatively cyclohexylalanine
- --Y is any D- or L-amino acid residue and (b)
- one or more of the peptide links between Tyr, X, Gly, B and Y is replaced by a group or groups, the same or different, selected from --CH(OH)--CH.sub.2 --, --CH(OR)--CH.sub.2 --, --CH.sub.2 NH--, ##STR34## --CH.sub.2 --NR--, --CO--CH.sub.2 --and (except where X-Gly and the Gly-Gly link is involved) --CH.sub.2 CH.sub.2 -- (where R is an aliphatic or other protective group) and/or any adjacent pair of peptide-bond nitrogen atoms of the backbone is linked to form the structure ##STR35## that is to say a carbonyl or thiocarbonyl group links the nitrogen atoms of adjacent amino acid residues, A and A' being the side chains thereof and optionally further with the nitrogen of one or more remaining peptide groups carrying a protective aliphatic or other group as ##STR36## where R is as below and (c) Z is --NH.sub.2, --NHR, --N(R).sub.2, --OH or --OR where R is as below and (d)
- R is an aliphatic or other protective group.
The compound ##STR40## wherein Z' is benzyloxycarbonyl ##STR41##
The compound:
- ##STR42##
The compound:
- ##STR44##
The compound:
- ##STR46##
The compound:
- ##STR47##
The compound:
- ##STR48##
The compound:
- ##STR50##
The compound:
- ##STR52##
A compound according to any one of the preceding claims, as such or in pharmaceutically acceptable N-protected or salt form, when made up with a pharmaceutically acceptable diluent or carrier for administration.
Dependencies are inferred from the claim text.