US4431635A
Expired / Lapsed
US
⏱️ 0.0 years remaining
LH-RH Antagonists
Assignee: Individual
•
Filing: 1982-01-20
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Granted: 1984-02-14
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Expires: 2002-01-20
Abstract
Abstract Disclosed herein are peptide analogs of the luteinizing hormone releasing hormone (LH-RH) which are potent antagonists of LHRH. The analogs differ in structure from LH-RH by having different amino acid residues at positions 1, 2 and 6, and optionally at positions 3 and 10. Methods for preparing and using these analogs are described.
Inventors
- 👤 David H. Coy
- 👤 Andrew V. Shally
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-11-05 07:32
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
Claims Analysis
Total Claims: 10
Claim 1
Independent Claim
156 words
A compound of formula I: X-R.sup.1 -R.sup.2 -R.sup.3 -Ser-Tyr-R.sup.4 -Leu-Arg-Pro-R.sup.5 -NH.sub.2 (I) in which X is hydrogen, lower alkanoyl, HOOC-(CH 2 ) n -CO wherein n is an integer from 2 to 6, benzoyl or the acyl portion of a D- or L-amino acid; R 1 is Gly,L-Ala,D-Ala, or D-Phe having a substituent in the para position of the phenyl group selected from the group consisting of nitro, amino, methyl, cyano, trifluoromethyl, hydroxy and methoxy; R 2 is D-Phe having a substituent in the para position of the phenyl group selected from the group consisting of halo, nitro, amino, methyl, cyano, trifluoromethyl, hydroxy and methoxy; R 3 is D-Trp,L-Trp or L-Phe; R 4 is D-Trp,D-Phe or D-Phe having a substituent in the para position of the phenyl group selected from the group consisting of halo, nitro, amino, methyl, cyano, trifluoromethyl, hydroxy and methoxy; and R 5 is Gly or D-Ala; or a therapeutically acceptable salt thereof.
Claim 2
Dependent Claim
156 words
A compound of formula I: X-R.sup.1 -R.sup.2 -R.sup.3 -Ser-Tyr-R.sup.4 -Leu-Arg-Pro-R.sup.5 -NH.sub.2 (I) in which X is hydrogen, lower alkanoyl, HOOC-(CH 2 ) n -CO wherein n is an integer from 2 to 6, benzoyl or the acyl portion of a D- or L-amino acid; R 1 is Gly,L-Ala,D-Ala, or D-Phe having a substituent in the para position of the phenyl group selected from the group consisting of nitro, amino, methyl, cyano, trifluoromethyl, hydroxy and methoxy; R 2 is D-Phe having a substituent in the para position of the phenyl group selected from the group consisting of halo, nitro, amino, methyl, cyano, trifluoromethyl, hydroxy and methoxy; R 3 is D-Trp,L-Trp or L-Phe; R 4 is D-Trp,D-Phe or D-Phe having a substituent in the para position of the phenyl group selected from the group consisting of halo, nitro, amino, methyl, cyano, trifluoromethyl, hydroxy and methoxy; and R 5 is Gly or D-Ala; or a therapeutically acceptable salt thereof.
Claim 3
Dependent Claim
11 words
The compound of claim 1, in which R 5 is D-Ala.
Claim 4
Dependent Claim
117 words
The compound of claim 1, in which X is hydrogen, lower alkanoyl, HOOC-(CH 2 ) n -CO wherein n is an integer from 2 to 6, benzoyl or the acyl portion of an amino acid residue of alanine, arginine, asparagine, cysteine, glutamine, glycine, histidine, isoleucine, leucine, lysine, methionine, ornithine, phenylalanine, proline, serine, threonine, tryptophan, tyrosine or valine; R 1 is D-p-Y-Phe wherein Y is selected from the group consisting of nitro, amino, methyl, cyano, trifluoromethyl, hydroxy and methoxy; R 2 is D-p-Y-Phe in which Y is as defined herein; R 3 is D-Trp; R 4 is D-Trp,D-Phe or D-p-Y-Phe in which Y is as defined herein; and R 5 is D-Ala; or a therapeutically acceptable salt thereof.
Claim 5
Dependent Claim
52 words
The compound of claim 1, in which X is hydrogen, lower alkanoyl or HOOC-(CH 2 ) n -CO wherein n is an integer from 2 to 6; R 2 is D-p-halo-Phe; R 3 is D-Trp; R 4 is D-Trp or D-Phe; and R 5 is D-Ala; or a therapeutically acceptable salt thereof.
Claim 6
Dependent Claim
44 words
The compound of claim 1, in which X is acetyl or HOOCCH 2 -CH 2 CO, R 2 is D-p-Cl-Phe; D-p-Br-Phe or D-p-F-Phe; R 3 is D-Trp; R 4 is D-Trp or D-Phe; and R 5 is D-Ala; or a therapeutically acceptable salt thereof.
Claim 7
Dependent Claim
27 words
A gonadotropin antagonizing pharmaceutical composition comprising a gonadotropin antagonizing amount of the compound of claim 1 or a therapeutically acceptable salt thereof, and a pharmaceutically acceptable carrier.
Claim 8
Dependent Claim
19 words
The compound of claim 1 which is N-Ac-Ala 1 , D-p-Cl-Phe 2 , D-Trp 3 ,6 -D-Ala 10 -LH-RH.
Claim 9
Dependent Claim
15 words
The compound of claim 1 which is N-Ac-D-Ala 1 ,10,-D-p-Cl-Phe 2 ,D-Trp 3 ,6 -LH-RH.
Claim 10
Dependent Claim
17 words
The compound of claim 1 which is N-Ac-Gly 1 ,-D-p-Cl-Phe 2 ,D-Trp 3 ,6 -D-Ala 10 -LH-RH.
References Cited (Backward Citations)
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USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1987-02-13 | 1987-08-15 | 1988-02-14 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1991-02-13 | 1991-08-15 | 1992-02-14 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 1995-02-13 | 1995-08-15 | 1996-02-14 | $7700.00 | Window Closed / Lapsed |