Novel tetradecapeptides, intermediates therefor, and compositions and methods employing said tetradecapeptides

Claim 2

Nove tetradecapeptides represented by the formula H-Tyr-X-Gly-Phe-Met-Thr-Ser-Glu-Lys-Ser-Gln-Thr-Pro-Leu-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-tyrosin, 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; Y is selected from the group consisting of hydroxy, amino, loweralkylamino, diloweralkylamino, and lower alkoxy; and the pharmaceutically acceptable salts thereof.

Claim 3

The tetradecapetides of claim 1 wherein Y is hydroxy

Claim 4

The tetradecapetides of claim 1 wherein Y is amino.

Claim 5

The tetradecapeptides of claim 1 wherein Y is loweralkylamino.

Claim 6

The tetradecapeptides of claim 1 wherein Y is diloweralkylamino.

Claim 7

The tetradecapeptides of claim 1 wherein Y is lower alkoxy.

Claim 8

Noval tetradecapeptides represented by the formula H-Tyr-D-Ala-Gly-Phe-Met-Thr-Ser-Glu-Lys-Ser-Gln-Thr-Pro-Leu-Y wherein Y is selected from the group consisting of hydroxy, amino, loweralkylamino, diloweralkylamino and lower alkoxy; and the pharmaceutically acceptable salts thereof.

Claim 9

Noval tetradecapeptides represented by the formula H-Tyr-D-Ala-Gly-Phe-Met-Thr-Ser-Glu-Lys-Ser-Gln-Thr-Pro-Leu-Y wherein Y is selected from the group consisting of hydroxy, amino, loweralkylamino, diloweralkylamino and lower alkoxy; and the pharmaceutically acceptable salts thereof.

Claim 10

The tetradecapeptides of claim 7 wherein Y is loweralkylamino.

Claim 11

The tetradecapetides of claim 7 wherein Y is diloweralkylamino.

Claim 12

The tetradecapeptides of claim 7 wherein Y is lower alkoxy.

Claim 13

D-Ala 2 β-lipotropin fragment 61-74 or a pharmaceutically acceptable salt thereof.

Claim 14

D-Ala 2 β-lipotropin fragment 61-74 or a pharmaceutically acceptable salt thereof.

Claim 15

D-Ala 2 -β-lipotropin fragment 61-74 amide or a pharmaceutically acceptable salt thereof.

Claim 16

D-Ala 2 -β-lipotropin fragment 61-74 amide or a pharmaceutically acceptable salt thereof.

Claim 17

A pharmaceutical composition suitable for oral, parenteral, nasal, rectal or vaginal or sublingual administration comprising a therapeutically effective amount of a compound of claim 1 and a pharmaceutically acceptable carrier or diluent.

Claim 18

A pharmaceutical composition in accordance with claim 13 adapted for oral administration.

Claim 19

A pharmaceutical composition in accordance with claim 13 adapted for parenteral administration.

Claim 20

A pharmaceutical composition in accordance with claim 13 adapted for nasal administration.

Claim 21

A pharmaceutical composition in accordance with claim 13 adapted for rectal administration.

Claim 22

A pharmaceutical composition in accordance with claim 13 adapted for vaginal administration.

Claim 23

A pharmaceutical composition in accordance with claim 13 adapted for sublingual administration.

Claim 24

A tetradecapeptide 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)-Lys(R.sub. 5)-Ser(R.sub. 3)-Gln-Thr(R.sub.3)-Pro-Leu-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-argine, X is a chiral amino acid residue protected ty an R 2 , R 3 , R 4 , R 5 , R 6 protecting group; R 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 2 is a protecting group for the phenolic hydroxyl group of tyrosine selected from the group consisting of tetrahydropyranyl, tert-butyl, trityl, benzyl, 2,4-dichlorobenzyl, benzyloxycarbonyl or 2-bromobenzyloxycarbonyl; R 3 is a protecting group for the alcohol hydroxy functions of serine abd threonine; R 4 is a protecting group for the gamma carboxyl group of glutamic acid; R 5 is a protecting group for the epsilon amino group of lysine selected from the group consisting of trifluoracetyl, benzyloxycarbonyl, and 1-chlorobenzyloxycarbony; and R 6 is a protecting group for the quanidine 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##

Claim 25

A tetradecapeptide 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)-Lys(R.sub. 5)-Ser(R.sub. 3)-Gln-Thr(R.sub.3)-Pro-Leu-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-argine, X is a chiral amino acid residue protected ty an R 2 , R 3 , R 4 , R 5 , R 6 protecting group; R 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 2 is a protecting group for the phenolic hydroxyl group of tyrosine selected from the group consisting of tetrahydropyranyl, tert-butyl, trityl, benzyl, 2,4-dichlorobenzyl, benzyloxycarbonyl or 2-bromobenzyloxycarbonyl; R 3 is a protecting group for the alcohol hydroxy functions of serine abd threonine; R 4 is a protecting group for the gamma carboxyl group of glutamic acid; R 5 is a protecting group for the epsilon amino group of lysine selected from the group consisting of trifluoracetyl, benzyloxycarbonyl, and 1-chlorobenzyloxycarbony; and R 6 is a protecting group for the quanidine 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##