Novel octapeptides, intermediates therefor, and compositions and methods employing said octapeptides
OwnerDavid H. Coy, Abba J. Kastininventors
Life of this patent
Estimating the term…
Abstract
Novel octapeptides having the following amino acid sequence: H-Tyr-X-Gly-Phe-Met-Thr-Ser-Glu-Y wherein: X is a chiral residue of a D-amino acid selected from the group consisting of D-alanine, D-leucine, D-isoleucine, D-valine, D-phenylalanine, D-tyrosine, D-tryptophan, D-serine, D-threonine, D-methionine, D-glutamic acid, D-glutamine, D-proline D-aspartic acid, D-asparagine, D-lysine, D-arginine and D-histidine; and Y is selected from the group consisting of hydroxy, amino, loweralkylamino, diloweralkylamino and lower alkoxy; and the pharmaceutically acceptable salts thereof; intermediates useful in making the novel compounds; the pharmaceutical compositions and methods employing the novel compounds.
Claims20
Novel octapeptides represented by the formula:
- H-Tyr-X-Gly-Phe-Met-Thr-Ser-Glu-Y
- wherein X is a D-amino acid selected from the group consisting of D-alanine, D-leucine, D-isoleucine, D-valine, D-phenylalanine, D-tyrosine, D-tryptophan, D-serine, D-histidine, D-threonine, D-methionine, D-glutamic acid, D-glutamine, D-aspartic acid, D-asparagine, D-lysine, or D-arginine;
- and Y is selected from the group consisting of hydroxy, amino, aminoloweralkyl, aminodiloweralkyl or lower alkoxy, or a pharmaceutically acceptable salt thereof.
Novel octapeptides represented by the formula:
- H-Tyr-D-Ala-Gly-Phe-Met-Thr-Ser-Glu-Y
- wherein Y is selected from the group consisting of hydroxy, amino, loweralkylamino, diloweralkylamino or lower alkoxyl;
- or a pharmaceutically acceptable salt thereof.
D-Ala.sup.2 -.beta. -lipotropin fragment 61-68 or a pharmaceutically acceptable salt thereof.
D-Ala.sup.2 -.beta. -lipotropin fragment 61-.epsilon.amide or a pharmaceutically acceptable salt thereof.
Novel octapeptides of the formula:
- R.sub.1 -Tyr(R.sub.2)-X'-Gly-Phe-Met-Thr(R.sub.3)-Ser(R.sub.3)-Glu(R.sub.4)-Y
- wherein
- X' is a chiral residue of a D-amino acid selected from the group consisting of D-alanine, D-leucine, D-isoleucine, D-valine, D-phenylalanine, D-tyrosine, D-tryptophan, D-serine, D-histidine, D-proline, D-threonine, D-methionine, D-glutamic acid, D-glutamine, D-aspartic acid, D-asparagine, D-lysine and D-arginine with the limitation that when x' is D-tyrosine, D-threonine, D-serine, D-glutamine, D-lysine, D-aspartic acid or D-arginine, X' is a chiral amino acid residue protected by an R.sub.2, R.sub.3, R.sub.4, R.sub.5, R.sub.6 protecting group;
- R.sub.1 is a N-terminus solid phase peptide synthesis protecting group selected from the group consisting of acyl-type protecting groups, aromatic urethan-type protecting groups, alkyl-type protecting groups, trialkylsilane groups, or aliphatic urethan protecting groups;
- R.sub.2 is a protecting group for the phenolic hydroxyl group of tyrosine selected from the group consisting of tetrahydropyranol, tert-butyl, trityl, benzyl, 2,4-dichlorobenzyl, benzyloxycarbonyl or 2-bromobenzyloxycarbonyl;
- R.sub.3 is a protecting group for the alcohol hydroxy functions of serine and threonine;
- R.sub.4 is a protecting group for the gamma carboxyl group of glutamic acid;
- R.sub.5 is a protecting group for the epsilon amino group of lysine selected from the group consisting of trifluoracetyl, benzloxycarbonyl, and 2-chlorobenzyloxycarbonyl;
- and
- R.sub.6 is a protecting group for the guanidine group of arginine;
- Y is selected from the group consisting of hydroxy, amino, loweralkylamino, diloweralkylamino, or lower alkoxy and a derivatized insoluble polystyrene resin support represented by the formulae ##STR2##
Dependencies are inferred from the claim text.