Patent US4018726A successfully refreshed from Google Patents.
US4018726A
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[D-Phe6 ]-LH-RH and intermediates therefor
Assignee: Individual
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Filing: 1975-06-12
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Granted: 1977-04-19
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Expires: 1995-06-12
Abstract
Abstract The decapeptide [D-Phe 6 ]-LH-RH, salts thereof, and intermediates used for the synthesis thereof are disclosed. The decapeptide has potent LH- and FSH-releasing hormone properties.
Inventors
- 👤 Andrew Victor Schally
- 👤 David Howard Coy
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-25 18:03
CPC Classifications
C; C07; C07K; C07K7/00; C07K7/04; C07K7/23; A; A61; A61K; A61K38/00; Y; Y10; Y10S; Y10S930/00; Y10S930/01; Y10S930/13; Y10S930/28
Claims Analysis
Total Claims: 10
Claim 1
Independent Claim
155 words
A compound of the formula R 6 -(pyro)-Glu-His(N lm -R 5 )-Trp-Ser(R 4 )-Tyr(R 3 )-D-Phe-Leu-Arg-(N G -R 2 )-Pro-Gly-R 1 in which R 1 is amino or O-(lower alkyl), R 2 is a protective group for the N.sup.δ, N.sup.ω, and N.sup.ω ' nitrogen atoms of arginine selected from the group consisting of tosyl, nitro benzyloxycarbonyl and adamantyloxycarbonyl; R 3 is a protective group for the hydroxyl of tyrosine selected from the group consisting of 2-bromobenzyloxycarbonyl, benzyl, acetyl, tosyl, benzoyl, t-butyl, tetrahydropyran-2-yl, trityl, 2,4-dichlorobenzyl and benzyloxycarbonyl; R 4 is a protective group for the hydroxyl group of serine and is selected from the group defined hereinbefore for R 3 ; R 5 is a protective group for the imidazole nitrogen atoms of histidine selected from the group of dinitrophenyl, tosyl, 2,2,2-trifluoro-1-benzoyloxycarbonylaminoethyl and 2,2,2-trifluoro-t-butyloxycarbonylaminoethyl; and R 6 is hydrogen or an α-amino protective group selected from the group consisting of t-butyloxycarbonyl, benzyloxycarbonyl, cyclopentyloxycarbonyl, t-amyloxycarbonyl and d-isobornyloxycarbonyl.
Claim 2
Dependent Claim
155 words
A compound of the formula R 6 -(pyro)-Glu-His(N lm -R 5 )-Trp-Ser(R 4 )-Tyr(R 3 )-D-Phe-Leu-Arg-(N G -R 2 )-Pro-Gly-R 1 in which R 1 is amino or O-(lower alkyl), R 2 is a protective group for the N.sup.δ, N.sup.ω, and N.sup.ω ' nitrogen atoms of arginine selected from the group consisting of tosyl, nitro benzyloxycarbonyl and adamantyloxycarbonyl; R 3 is a protective group for the hydroxyl of tyrosine selected from the group consisting of 2-bromobenzyloxycarbonyl, benzyl, acetyl, tosyl, benzoyl, t-butyl, tetrahydropyran-2-yl, trityl, 2,4-dichlorobenzyl and benzyloxycarbonyl; R 4 is a protective group for the hydroxyl group of serine and is selected from the group defined hereinbefore for R 3 ; R 5 is a protective group for the imidazole nitrogen atoms of histidine selected from the group of dinitrophenyl, tosyl, 2,2,2-trifluoro-1-benzoyloxycarbonylaminoethyl and 2,2,2-trifluoro-t-butyloxycarbonylaminoethyl; and R 6 is hydrogen or an α-amino protective group selected from the group consisting of t-butyloxycarbonyl, benzyloxycarbonyl, cyclopentyloxycarbonyl, t-amyloxycarbonyl and d-isobornyloxycarbonyl.
Claim 3
Dependent Claim
11 words
The compound of claim 1 in which R 1 is amino.
Claim 4
Dependent Claim
31 words
The compound of claim 1 wherein R 1 is amino, R 2 is tosyl, R 3 is 2-bromo-benzyloxycarbonyl, R 4 is benzyl, R 5 is tosyl and R 6 is hydrogen.
Claim 5
Dependent Claim
11 words
The compound L-pyroglutamyl-L-histidyl-L-tryptophyl-L-seryl-L-tyrosyl-D-phenylalanyl-L-leucyl-L-arginyl-L-prolylglycinamide, or a non-toxic, pharmaceutically acceptable addition salt thereof.
Claim 6
Dependent Claim
11 words
The compound L-pyroglutamyl-L-histidyl-L-tryptophyl-L-seryl-L-tyrosyl-D-phenylalanyl-L-leucyl-L-arginyl-L-prolylglycinamide, or a non-toxic, pharmaceutically acceptable addition salt thereof.
Claim 7
Dependent Claim
210 words
A compound selected from the group consisting of R 6 -(pyro)-Glu-His-(N 1m -R 5 )-Trp-Ser(R 4 )-Tyr(R 3 )-D-Phe-Leu-Arg(N G -R 2 )-Pro-Gly-A, R 7 -His(N 1m -R 5 )-Trp-Ser(R 4 )-Tyr-(R 3 )-D-Phe-Leu-Arg(N G -R 2 )-Pro-Gly-A, R 7 -Trp-Ser(R 4 )-Tyr-(R 3 )-D-Phe-Leu-Arg(N G -R 2 )-Pro-Gly-A, R 7 -Ser(R 4 )-Tyr(R 3 )-D-Phe-Leu-Arg(N G -R 2 )-Pro-Gly-A, R 7 -Tyr(R 3 )-D-Phe-Leu-Arg-(N G -R 2 )-Pro-Gly-A, and R 7 -D-Phe-Leu-Arg(N G -R 2 )-Pro-Gly-A, in which R 2 is a protective group for the N.sup.δ, N.sup.ω, and N.sup.ω ' nitrogen atoms of arginine selected from the group consisting of tosyl, nitro, benzyloxycarbonyl and adamantyloxycarbonyl; R 3 is a protective group for the hydroxyl of tyrosine selected from the group consisting of 2-bromo-benzyloxycarbonyl, benzyl, acetyl, tosyl, benzoyl, t-butyl, tetrahydropyran-2-yl, trityl, 2,4-dichlorobenzyl and benzyloxycarbonyl; R 4 is a protective group for the hydroxyl group of serine and is selected from the group defined hereinbefore for R 3 ; R 5 is a protective group for the imidazole nitrogen atoms of histidine selected from the group of dinitrophenyl, tosyl, 2,2,2-trifluoro-1-benzoyloxycarbonylaminoethyl and 2,2,2-trifluoro-t-butyloxycarbonylaminoethyl; and R 6 is hydrogen or an α-amino protective group and R 7 is an α-amino protective group, and A is selected from the class consisting of: ##STR3##
Claim 8
Dependent Claim
210 words
A compound selected from the group consisting of R 6 -(pyro)-Glu-His-(N 1m -R 5 )-Trp-Ser(R 4 )-Tyr(R 3 )-D-Phe-Leu-Arg(N G -R 2 )-Pro-Gly-A, R 7 -His(N 1m -R 5 )-Trp-Ser(R 4 )-Tyr-(R 3 )-D-Phe-Leu-Arg(N G -R 2 )-Pro-Gly-A, R 7 -Trp-Ser(R 4 )-Tyr-(R 3 )-D-Phe-Leu-Arg(N G -R 2 )-Pro-Gly-A, R 7 -Ser(R 4 )-Tyr(R 3 )-D-Phe-Leu-Arg(N G -R 2 )-Pro-Gly-A, R 7 -Tyr(R 3 )-D-Phe-Leu-Arg-(N G -R 2 )-Pro-Gly-A, and R 7 -D-Phe-Leu-Arg(N G -R 2 )-Pro-Gly-A, in which R 2 is a protective group for the N.sup.δ, N.sup.ω, and N.sup.ω ' nitrogen atoms of arginine selected from the group consisting of tosyl, nitro, benzyloxycarbonyl and adamantyloxycarbonyl; R 3 is a protective group for the hydroxyl of tyrosine selected from the group consisting of 2-bromo-benzyloxycarbonyl, benzyl, acetyl, tosyl, benzoyl, t-butyl, tetrahydropyran-2-yl, trityl, 2,4-dichlorobenzyl and benzyloxycarbonyl; R 4 is a protective group for the hydroxyl group of serine and is selected from the group defined hereinbefore for R 3 ; R 5 is a protective group for the imidazole nitrogen atoms of histidine selected from the group of dinitrophenyl, tosyl, 2,2,2-trifluoro-1-benzoyloxycarbonylaminoethyl and 2,2,2-trifluoro-t-butyloxycarbonylaminoethyl; and R 6 is hydrogen or an α-amino protective group and R 7 is an α-amino protective group, and A is selected from the class consisting of: ##STR3##
Claim 9
Dependent Claim
13 words
The compound according to claim 5 in which A is a benzhydrylamine resin.
Claim 10
Dependent Claim
51 words
The compound of claim 5 having the formula R 6 -(pryo)-Glu-His-(N 1m -R 5 )-Trp-Ser(R 4 )-Tyr(R 3 )-D-Phe-Leu-Arg(N G -R 2 )-Pro-Gly-A in which R 2 is tosyl, R 3 is 2-bromo-benzyloxycarbonyl, R 4 is benzyl, R 5 is tosyl, R 6 is hydrogen and A is a benzhydrylamine resin.
References Cited (Backward Citations)
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