EP0026640A2
Expired / Lapsed
EP
⏱️ 0.0 years remaining
Long lasting agonists and antagonists of LHRH and compositions containing them
Assignee: Merck and Co Inc
•
Filing: 1980-09-25
•
Granted: —
•
Expires: 2000-09-25
Abstract
Abstract Novel peptides have the formula: in which A is (L or D)- pyroGlu, an (L or D)- (N-acetyl or N-pyroGlu) imino acid; acetyl D-Phe; or (C 3 - 7 cycloalkyl)-acyl; B is His; Gly; or an L or D aromatic or aliphatic amino acid; or is absent; C is an (L or D) aromatic or aliphatic amino acid; D is Ser, Thr, or Ala; E is an aromatic amino acid; F is an amino acid with a basic side chain; G is an imino acid or aliphatic amino acid; X is GlyNH 2 ; AlaNH 2 ; aminoethyl; aminopropyl; or aminohydroxyethyl; Y is hydrogen or C 1-4 alkyl; and n is 2 or3. Such peptides have long-lasting LHRH agonist and antagonist activity and are useful in promoting and reducing fertility. They may be included in suitable pharmaceutical compositions. Novel intermediate compounds have formulae: Compounds of formula: are made by alkylating basifying, and if necessary removing the protecting group from, compounds of formula: In these formulae, A is hydrogen or R 3 -O-CO-, R 2 is C 1-4 alkyl and R 3 is C 1-12 alkyl or C 1-4 aralkyl.
Inventors
- 👤 Daniel F. Veber
- 👤 Roger M. Freidinger
Bibliographic Details
Application Number
—
Jurisdiction
EP
Data Source
google_patents
Last Synchronized
2026-10-29 20:13
CPC Classifications
C; C07; C07D; C07D207/00; C07D207/02; C07D207/18; C07D207/22; C07D207/24; C07D207/26; C07D207/273; A; A61; A61P; A61P5/00; C07K; C07K7/00; C07K7/04; C07K7/23; A61K; A61K38/00; Y; Y02; Y02P; Y02P20/00; Y02P20/50; Y02P20/55; Y10; Y10S; Y10S930/00; Y10S930/01; Y10S930/13
Claims Analysis
Total Claims: 14
Claim 1
Independent Claim
114 words
1 A peptide of the formula: in which A is (L or D)- pyroGlu, an (L or D)- (N-acetyl or N-pyroGlu)imino acid; acetyl D- P he; or (C 3-7 cycloalkyl)-acyl; B is His; Gly; or an L or D aromatic or aliphatic amino acid; or is absent; C is an (L or D) aromatic or aliphatic amino acid; D is Ser, Thr, or Ala; E is an aromatic amino acid; F is an amino acid with a basic side chain; G is an imino acid or aliphatic amino acid; X is GlyNH 2 ; AlaNH 2 ; aminoethyl; aminopropyl; or aminohydroxyethyl; Y is hydrogen or C l-4 alkyl; and n is 2 or 3.
Claim 2
Dependent Claim
114 words
1 A peptide of the formula: in which A is (L or D)- pyroGlu, an (L or D)- (N-acetyl or N-pyroGlu)imino acid; acetyl D- P he; or (C 3-7 cycloalkyl)-acyl; B is His; Gly; or an L or D aromatic or aliphatic amino acid; or is absent; C is an (L or D) aromatic or aliphatic amino acid; D is Ser, Thr, or Ala; E is an aromatic amino acid; F is an amino acid with a basic side chain; G is an imino acid or aliphatic amino acid; X is GlyNH 2 ; AlaNH 2 ; aminoethyl; aminopropyl; or aminohydroxyethyl; Y is hydrogen or C l-4 alkyl; and n is 2 or 3.
Claim 3
Dependent Claim
69 words
2 A peptide according to claim 1 in which A is (L or D) N-acetyl-Pro, N-acetyl-Hyp,N-pyroGlu-Pro, or N-pyroGlu-Hyp; B is (L or D)- Phe, Trp, Tyr, His, Ala, Leu, Ile, or Val; C is (L or D) Phe, Trp, Tyr, His, Ala, Leu, Ile, or Val; E is Phe, Trp, Tyr or His; F is Lys, Arg, or Orn; and G is Pro, Hyp, Ala, Leu, Ile, or Val.
Claim 4
Dependent Claim
42 words
3 A peptide according to claim 1 in which A is pyroGlu; B is His, C is Trp; D is Ser; E is Tyr; F is Arg; G is pro; X is GlyNH 2 ; Y is isopropylmethyl; and n is 2.
Claim 5
Dependent Claim
41 words
4 A peptide according to claim 1 in which A is pyroGlu; B is His; C is Trp; D is Ser; E is Tyr; F is Arg; G is p ro; X is aminoethyl; Y is isopropylmethyl; and n is 2.
Claim 6
Dependent Claim
22 words
5 A pharmaceutical composition comprising a non-toxic, pharmaceutically acceptable carrier and a therapeutically effective amount of a peptide according to claim 1.
Claim 7
Dependent Claim
47 words
6 For use in the control of fertility, a therapeutically effective amount of a peptide of the formula set forth in claim 1 in which A is pyroGlu; B is His; C is an aromatic amino acid; and the other variables are as defined in claim 1.
Claim 8
Dependent Claim
85 words
7 For use in reducing fertility, a therapeutically effective amount of a peptide of the formula set forth in claim 1 in which A is L or D pyroGlu, an (L or D)- (N-acetyl or N-pyroGlu) imino acid; acetyl D-Phe; or C3-7 cycloalkylacyl; B is Gly, an L or D aromatic amino acid, or an L or D aliphatic amino acid; or is absent; C is an L or D aromatic or aliphatic amino acid; and the other variables are as defined in claim 1.
Claim 9
Dependent Claim
111 words
8 A method of preparing a compound of the formula: where A is hydrogen or and R 2 is C 1-4 alkyl, and R 3 is C 1-12 alkyl or C 1-4 aralkyl, comprising (a) treating an protected Met-aliphatic amino acid ester of the formula: with an alkylating agent, whereby the corresponding sulfonium salt is produced; (b) treating the sulfonium salt prepared in Step (a) with a strong base in order to effect ring closure and prepare the compound of formula (VIII) in which A is and optionally (c) cleaving the protecting group from the compound of formula (VIII) to prepare the compound of formula (VIII) in which A is hydrogen.
Claim 10
Dependent Claim
111 words
8 A method of preparing a compound of the formula: where A is hydrogen or and R 2 is C 1-4 alkyl, and R 3 is C 1-12 alkyl or C 1-4 aralkyl, comprising (a) treating an protected Met-aliphatic amino acid ester of the formula: with an alkylating agent, whereby the corresponding sulfonium salt is produced; (b) treating the sulfonium salt prepared in Step (a) with a strong base in order to effect ring closure and prepare the compound of formula (VIII) in which A is and optionally (c) cleaving the protecting group from the compound of formula (VIII) to prepare the compound of formula (VIII) in which A is hydrogen.
Claim 11
Dependent Claim
24 words
9 A compound of the formula: where R 2 is C 1-4 alkyl and R 3 is C 1-12 alkyl or C 1-4 aralkyl.
Claim 12
Dependent Claim
24 words
9 A compound of the formula: where R 2 is C 1-4 alkyl and R 3 is C 1-12 alkyl or C 1-4 aralkyl.
Claim 13
Dependent Claim
13 words
10 A compound of the formula: where R 2 is C 1-4 alkyl.
Claim 14
Dependent Claim
13 words
10 A compound of the formula: where R 2 is C 1-4 alkyl.
References Cited (Backward Citations)
No citation records indexed.
USPTO Annuity & Maintenance Windows
Maintenance schedule is calculated for granted US utility patents.