EP0175506A2
Expired / Lapsed
EP
⏱️ 0.0 years remaining
GnRH antagonists
Assignee: Salk Institute for Biological Studies
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Filing: 1985-08-23
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Granted: —
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Expires: 2005-08-23
Abstract
Abstract Peptides which inhibit the secretion of gonadotropins by the pituitary gland and inhibit the release of steroids by the gonads. Administration of an effective amount prevents ovulation of female mammalian eggs and/or release of steroids by the gonads. The peptides have the structure: X-R 1 -(W)D-Phe--R 3 R 4 -R 5 -R 6 (V)-R 7 -Arg-Pro-R 10 wherein X is hydrogen or an acyl group having 7 or less carbon atoms; R 1 is dehydro-Pro, Pro, D-pGlu, D-Phe, D-Trp or β-D-NAL; W is F, Cl, Cl 2 , Br, N0 2 or C a Me-Cl; R 3 is D-Trp, (N in For(D)-Trp or D-Trp which is substituted in the 5- or 6-position with N0 2 , NH 2 , OCH 3 , F, Cl, Br or CH 3 ; R 4 is Ser, Orn, AAL or aBu; R 5 is Tyr, (3F)Phe, (2F)Phe, (31)Tyr, (3CH 3 )Phe, (2CH 3 )Phe, (3Cl)Phe or (2Cl)Phe; R 6 is D-Lys, D-Orn or D-Dap; V is (arg-R',R") n (X), with n being 1 to 5 and R' and R" being H, methyl, ethyl, propyl or butyl; R 7 is Leu, NML, Nle or Nva; and R 10 is Gly-NH 2 , D-Ala-NH 2 or NH-Y, with Y being lower alkyl, cycloalkyl, fluoro lower alkyl or NH--CONH-Q, where Q is H or lower alkyl.
Inventors
- 👤 Wylie Walker Vale, Jr.
- 👤 Jean Edouard Frederic Rivier
Bibliographic Details
Application Number
—
Jurisdiction
EP
Data Source
google_patents
Last Synchronized
2026-11-04 17:56
CPC Classifications
C; C07; C07K; C07K14/00; C07K7/00; C07K7/04; C07K7/23; A; A61; A61P; A61P5/00; A61K; A61K38/00; Y; Y10; Y10S; Y10S930/00; Y10S930/01; Y10S930/13
Claims Analysis
Total Claims: 26
Claim 1
Independent Claim
186 words
A peptide or a nontoxic salt thereof, said peptide having the formula: X-R 1 -(W)D-Phe-R 3 -R 4 -R 5 -R 6 (V)-R 7 -Arg-Pro-R 10 wherein X is hydrogen or an acyl group having 7 or less carbon atoms; R 1 is dehydro-Pro, Pro, D-pGlu, D-Phe, D-Trp or B-D-NAL; W is F, Cl, Cl 2 Br, N0 2 or CaMe-C l ; R 3 is D-Trp, (N in For)D-Trp or D-Trp which is substituted in the 5- or 6- position with NO 2 , NH 2 , OCH 3 , F, Cl, Br or CH 3 ; R 4 is Ser, Orn, AAL or aBu; R 5 is Tyr, (3F)Phe, (2F)Phe, (3I)Tyr, (3CH 3 )Phe, (2CH 3 )Phe, (3Cl)Phe or (2Cl)Phe; R 6 is D-Lys, D-Orn or D-Dap; V is (arg-R',R") (X), with n being 1 to 5 and R'and R" being H, methyl, ethyl, propyl or butyl; R 7 is Leu, NML, Nle or Nva; and R 10 is Gly-NH 2 , D-Ala-NH 2 or NH-Y, with Y being lower alkyl, cycloalkyl, fluoro lower alkyl or NH-CONH-Q, where Q is H or lower alkyl.
Claim 2
Dependent Claim
186 words
A peptide or a nontoxic salt thereof, said peptide having the formula: X-R 1 -(W)D-Phe-R 3 -R 4 -R 5 -R 6 (V)-R 7 -Arg-Pro-R 10 wherein X is hydrogen or an acyl group having 7 or less carbon atoms; R 1 is dehydro-Pro, Pro, D-pGlu, D-Phe, D-Trp or B-D-NAL; W is F, Cl, Cl 2 Br, N0 2 or CaMe-C l ; R 3 is D-Trp, (N in For)D-Trp or D-Trp which is substituted in the 5- or 6- position with NO 2 , NH 2 , OCH 3 , F, Cl, Br or CH 3 ; R 4 is Ser, Orn, AAL or aBu; R 5 is Tyr, (3F)Phe, (2F)Phe, (3I)Tyr, (3CH 3 )Phe, (2CH 3 )Phe, (3Cl)Phe or (2Cl)Phe; R 6 is D-Lys, D-Orn or D-Dap; V is (arg-R',R") (X), with n being 1 to 5 and R'and R" being H, methyl, ethyl, propyl or butyl; R 7 is Leu, NML, Nle or Nva; and R 10 is Gly-NH 2 , D-Ala-NH 2 or NH-Y, with Y being lower alkyl, cycloalkyl, fluoro lower alkyl or NH-CONH-Q, where Q is H or lower alkyl.
Claim 3
Dependent Claim
19 words
A peptide in accordance with Claim 1 wherein R 3 is (6NO 2 )D-Trp and R 6 is D-Lys.
Claim 4
Dependent Claim
15 words
A peptide in accordance with either Claim 1 or 2 wherein R 1 is B-D-2NAL.
Claim 5
Dependent Claim
19 words
A peptide in accordance with any one of Claims 1, 2 and 3 wherein V is Arg 3 (Ac).
Claim 6
Dependent Claim
14 words
A peptide in accordance with any one of Claims 1-4 wherein X is Ac.
Claim 7
Dependent Claim
17 words
A peptide in accordance with any one of Claims 1-5 wherein R 10 is D-Ala-NH 2 .
Claim 8
Dependent Claim
18 words
A peptide in accordance with any one of Claims 1-5 wherein R 10 is Gl y-NH 2 .
Claim 9
Dependent Claim
18 words
A peptide in accordance with Claim 1 wherein R 6 is D-Lys and V is Arg 3 (Ac).
Claim 10
Dependent Claim
16 words
A peptide in accordance with Claim 8 wherein X is Ac and R 1 is dehydro-Pro.
Claim 11
Dependent Claim
14 words
A peptide in accordance with Claim 1 having the formula: Ac-ß-D-2NAL-(4F)D-Phe-(6NO 2 ) D-Trp-Ser-Tyr-D-Lys(Arg3-Ac)-Leu-Arg-Pro-Gly-NH2.
Claim 12
Dependent Claim
16 words
A non-toxic salt of a peptide as claimed in any one of Claims 2 to 10.
Claim 13
Dependent Claim
6 words
Claims for the contracting state: AT
Claim 14
Independent Claim
263 words
A method for making a peptide or a nontoxic salt thereof, said peptide having the formula: X-R 1 -(W)D-Phe-R 3 -R 4 -R 5 -R 6 (V)-R -Arg-Pro-R 10 wherein X is hydrogen or an acyl group having 7 or less carbon atoms; R 1 is dehydro-Pro, Pro, D-pGlu, D-Phe, D-Trp or B-D-NAL; W is F, Cl, C1 2 Br, N0 2 or C a Me-Cl; R 3 is D-Trp, (N in For)D-Trp or D-Trp which is substituted in the 5- or 6-position with NO 2 , NH 2 , OCH 3 , F, Cl, Br or CH 3 ; R 4 is Ser, Orn, AAL or aBu; R 5 is Tyr, (3F)Phe, (2F)Phe, (3I)Tyr, ( 3CH3 ) Phe , (2CH 3 )Phe, (3Cl)Phe or (2Cl)Phe; R 6 is D-Lys, D-Orn or D-Dap; V is (arg-R',R") n (X), with n being 1 to 5 and R'and R" being H, methyl, ethyl, propyl or butyl; R 7 is Leu, NML, Nle or Nva; and R 10 is Gly-NH 2 , D-Ala-NH 2 or NH-Y, with Y being lower alkyl, cycloalkyl, fluoro lower alkyl or NH-CONH-Q, where Q is H or lower alkyl, which method comprises (a) forming an intermediate compound having formula X 1- R 1 -(W)D-Phe-R 3 (X 2 )-R 4 (X 3 )-R 5 (X 4 )-R 6 (V)-R 7 -Arg(X 5 )-Pro-X 6 ; (b) splitting off one or more of the groups X 1 to X 5 and/or cleaving from any resin support included in X 6 and, if desired, (c) converting a resulting peptide into a nontoxic salt thereof.
Claim 15
Independent Claim
263 words
A method for making a peptide or a nontoxic salt thereof, said peptide having the formula: X-R 1 -(W)D-Phe-R 3 -R 4 -R 5 -R 6 (V)-R -Arg-Pro-R 10 wherein X is hydrogen or an acyl group having 7 or less carbon atoms; R 1 is dehydro-Pro, Pro, D-pGlu, D-Phe, D-Trp or B-D-NAL; W is F, Cl, C1 2 Br, N0 2 or C a Me-Cl; R 3 is D-Trp, (N in For)D-Trp or D-Trp which is substituted in the 5- or 6-position with NO 2 , NH 2 , OCH 3 , F, Cl, Br or CH 3 ; R 4 is Ser, Orn, AAL or aBu; R 5 is Tyr, (3F)Phe, (2F)Phe, (3I)Tyr, ( 3CH3 ) Phe , (2CH 3 )Phe, (3Cl)Phe or (2Cl)Phe; R 6 is D-Lys, D-Orn or D-Dap; V is (arg-R',R") n (X), with n being 1 to 5 and R'and R" being H, methyl, ethyl, propyl or butyl; R 7 is Leu, NML, Nle or Nva; and R 10 is Gly-NH 2 , D-Ala-NH 2 or NH-Y, with Y being lower alkyl, cycloalkyl, fluoro lower alkyl or NH-CONH-Q, where Q is H or lower alkyl, which method comprises (a) forming an intermediate compound having formula X 1- R 1 -(W)D-Phe-R 3 (X 2 )-R 4 (X 3 )-R 5 (X 4 )-R 6 (V)-R 7 -Arg(X 5 )-Pro-X 6 ; (b) splitting off one or more of the groups X 1 to X 5 and/or cleaving from any resin support included in X 6 and, if desired, (c) converting a resulting peptide into a nontoxic salt thereof.
Claim 16
Dependent Claim
19 words
A process in accordance with Claim 1 wherein R 3 is (6NO 2 )D-Trp and R 6 is D-Lys.
Claim 17
Dependent Claim
15 words
A process in accordance with either Claim 1 or 2 wherein R 1 is B-D-2NAL.
Claim 18
Dependent Claim
16 words
A process in accordance with any one of Claims 1-3 wherein V is Arg 3 (Ac).
Claim 19
Dependent Claim
14 words
A process in accordance with any one of Claims 1-4 wherein X is Ac.
Claim 20
Dependent Claim
17 words
A process in accordance with any one of Claims 1-5 wherein R 10 is D-Ala-NH 2 .
Claim 21
Dependent Claim
17 words
A process in accordance with any one of Claims 1-5 wherein R 10 is Gly-NH 2 .
Claim 22
Dependent Claim
18 words
A process in accordance with Claim 1 wherein R 6 is D-Lys and V is Arg 3 (Ac).
Claim 23
Dependent Claim
16 words
A process in accordance with Claim 8 wherein X is Ac and R 1 is dehydro-Pro.
Claim 24
Dependent Claim
17 words
A process in accordance with Claim 1 having the formula: Ac-ß-D-2NAL-(4F)D-Phe-(6NO 2 )D-Trp-Ser-Tyr-D-Lys(Arg 3 -Ac)-Leu-Arg-Pro-Gly-NH 2 .
Claim 25
Dependent Claim
47 words
A method of contraceptive treatment of female mammalians which method comprises administering to a female mammalian an amount of a GnRH antagonist effective to suppress or delay ovulation, characterized in that said GnRH antagonist is a peptide as defined in Claim 1 or a non-toxic salt thereof.
Claim 26
Dependent Claim
45 words
A method of contraceptive treatment of male mammalians which method comprises administering to a male mammalian an amount of a GnRH antagonist effective to suppress spermatogenesis, characterized in that said GnRH antagonist is a peptide as defined in Claim 1 or a non-toxic salt thereof.
References Cited (Backward Citations)
No citation records indexed.
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