Des-(Ala1, Gly2), Met11 -SRIF and intermediates

Claim 2

A dodecapeptide selected from those of the formula ##STR4##in which A is D-tryptophyl of L-tryptophyl and the non-toxic acid addition salts thereof.

Claim 3

A peptide according to claim 1 which is: L-Cysteinyl-L-lysyl-L-asparaginyl-L-phenylalanyl-L-phenylalanyl-L-tryptophy-L-lysyl-L-threonyl-L-methionyl-L-threonyl-L-seryl-L-cysteine and a non-toxic acid addition salt thereof.

Claim 4

A peptide according to claim 1 which is: L-cysteinyl-L-lysyl-L-asparaginyl-L-phenylalanyl-L-phenylalanyl-D-tryptophyl-L-lysyl-L-threonyl-L-methionyl-L-threonyl-L-seryl-L-cysteine and a non-toxic acid addition salt thereof.

Claim 5

A peptide according to claim 1 which is: L-Cysteinyl-L-lysyl-L-asparaginyl-L-phenylalanyl-L-phenylalanyl-L-tryptophyl-L-lysyl-L-threonyl-L-methionyl-L-threonyl-L-seryl-L-cysteine (cyclic 1, 12 disulfide) and a non-toxic acid addition salt thereof.

Claim 6

A peptide according to claim 1 which is: L-Cysteinyl-L-lysyl-L-asparaginyl-L-phenylalanyl-L-phenylalanyl-D-tryptophyl-L-lysyl-L-threonyl-L-methionyl-L-threonyl-L-seryl-L-cysteine (cyclic 1, 12 disulfide) and a non-toxic acid addition salt thereof.

Claim 7

A compound of the formula R-L-Cys(R.sup.1)-L-Lys(R.sup.2)-L-Asn-L-Phe-L-Phe-A-L-Lys(R.sup.2)-L-Thr(R.sup.3)-L-Met-L-Thr(R.sup.3)-L-Ser(R.sup.4)-L-Cys(R.sup.1)-X wherein: A is L-tryptophyl or D-tryptophyl R is hydrogen, formyl, trifluoroacetyl, phthalyl, toluenesulfonyl, o-nitrophenylsulfenyl, benzyloxycarbonyl, p-methoxybenzyloxycarbonyl, p-nitrobenzyloxycarbonyl, 2-bromobenzyloxycarbonyl, 2-chlorobenzyloxycarbonyl, 1-(p-biphenylyl)-1-methyl-ethoxy carbonyl, tert-butyloxycarbonyl, diisopropylmethoxycarbonyl, allyloxycarbonyl, 2,2,2-trichloroethoxycarbonyl, amyloxycarbonyl, α,α-dimethylbenzyloxycarbonyl, α,α-dimethyl-3,5-dimethoxybenzyloxycarbonyl, benzhydryloxycarbonyl, 9-fluoroenylmethoxycarbonyl, isobornyloxycarbonyl, adamantyloxycarbonyl; R 1 is a protecting group for the sulfhydryl group of the two cysteinyl moieties independently selected from the group consisting of benzyl, 3,4-dimethylbenzyl, p-methoxybenzyl, p-nitrobenzyl, p-chlorobenzyl, trityl, benzhydryl, tetrahydropyranyl, acetamidomethyl, t-butylthio, ethylthio, ethylcarbamoyl, benzylthiomethyl or benzoyl; R 2 is formyl, trifluoroacetyl, phthalyl, toluenesulfonyl, o-nitrophenylsulfenyl, benzyloxycarbonyl, p-methoxybenzyloxycarbonyl, p-nitrobenzyloxycarbonyl, 2-bromobenzyloxycarbonyl, 2-chlorobenzyloxycarbonyl, 1(p-biphenylyl)-1-methyl-ethoxy carbonyl, tert-butyloxycarbonyl, diisopropylmethoxycarbonyl, allyloxycarbonyl, 2,2,2-trichloroethoxycarbonyl, amyloxycarbonyl, α,α-dimethylbenzyloxycarbonyl, α,α-dimethyl-3,5-dimethoxybenzyloxycarbonyl, benzhydryloxycarbonyl, 9-fluoroenylmethoxycarbonyl, isobornyloxycarbonyl, adamantyloxycarbonyl; R 3 and R 4 are protecting groups for the hydroxyl group of the threonyl and seryl moieties, independently selected from the group consisting of benzoyl, tert-butyl, benzyl. The preferred protecting group for R 3 and R 4 is benzyl; X is selected from the group consisting of OH, OCH 3 and an anchoring bond used in solid phase synthesis linked to a solid resin support represented by the formula ##STR5##said protecting groups defined by R 1 , R 2 , R 3 and R 4 being capable of being split off chemically under conditions that do not cleave said peptide chain and at least one of R, R 1 , R 2 , R 3 and R 4 being a protecting group when X is OH.

Claim 8

A compound of the formula R-L-Cys(R.sup.1)-L-Lys(R.sup.2)-L-Asn-L-Phe-L-Phe-A-L-Lys(R.sup.2)-L-Thr(R.sup.3)-L-Met-L-Thr(R.sup.3)-L-Ser(R.sup.4)-L-Cys(R.sup.1)-X wherein: A is L-tryptophyl or D-tryptophyl R is hydrogen, formyl, trifluoroacetyl, phthalyl, toluenesulfonyl, o-nitrophenylsulfenyl, benzyloxycarbonyl, p-methoxybenzyloxycarbonyl, p-nitrobenzyloxycarbonyl, 2-bromobenzyloxycarbonyl, 2-chlorobenzyloxycarbonyl, 1-(p-biphenylyl)-1-methyl-ethoxy carbonyl, tert-butyloxycarbonyl, diisopropylmethoxycarbonyl, allyloxycarbonyl, 2,2,2-trichloroethoxycarbonyl, amyloxycarbonyl, α,α-dimethylbenzyloxycarbonyl, α,α-dimethyl-3,5-dimethoxybenzyloxycarbonyl, benzhydryloxycarbonyl, 9-fluoroenylmethoxycarbonyl, isobornyloxycarbonyl, adamantyloxycarbonyl; R 1 is a protecting group for the sulfhydryl group of the two cysteinyl moieties independently selected from the group consisting of benzyl, 3,4-dimethylbenzyl, p-methoxybenzyl, p-nitrobenzyl, p-chlorobenzyl, trityl, benzhydryl, tetrahydropyranyl, acetamidomethyl, t-butylthio, ethylthio, ethylcarbamoyl, benzylthiomethyl or benzoyl; R 2 is formyl, trifluoroacetyl, phthalyl, toluenesulfonyl, o-nitrophenylsulfenyl, benzyloxycarbonyl, p-methoxybenzyloxycarbonyl, p-nitrobenzyloxycarbonyl, 2-bromobenzyloxycarbonyl, 2-chlorobenzyloxycarbonyl, 1(p-biphenylyl)-1-methyl-ethoxy carbonyl, tert-butyloxycarbonyl, diisopropylmethoxycarbonyl, allyloxycarbonyl, 2,2,2-trichloroethoxycarbonyl, amyloxycarbonyl, α,α-dimethylbenzyloxycarbonyl, α,α-dimethyl-3,5-dimethoxybenzyloxycarbonyl, benzhydryloxycarbonyl, 9-fluoroenylmethoxycarbonyl, isobornyloxycarbonyl, adamantyloxycarbonyl; R 3 and R 4 are protecting groups for the hydroxyl group of the threonyl and seryl moieties, independently selected from the group consisting of benzoyl, tert-butyl, benzyl. The preferred protecting group for R 3 and R 4 is benzyl; X is selected from the group consisting of OH, OCH 3 and an anchoring bond used in solid phase synthesis linked to a solid resin support represented by the formula ##STR5##said protecting groups defined by R 1 , R 2 , R 3 and R 4 being capable of being split off chemically under conditions that do not cleave said peptide chain and at least one of R, R 1 , R 2 , R 3 and R 4 being a protecting group when X is OH.

Claim 9

A compound according to claim 6 wherein X is ##STR6##

Claim 10

A compound according to claim 7 wherein R is t-butyloxycarbonyl, R 1 is p-methoxybenzyl, R 2 is benzyloxycarbonyl, R 3 is benzyl and R 4 is benzyl.