US4801577A
Expired / Lapsed
US
⏱️ 0.0 years remaining
Nonapeptide and decapeptide analogs of LHRH useful as LHRH antagonists
Assignee: Syntex USA LLC
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Filing: 1987-02-05
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Granted: 1989-01-31
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Expires: 2007-02-05
Abstract
Abstract Synthetic nona- and decapeptide LHRH antagonist analogs are disclosed, having a sterically hindered guanidino-substituted arginyl or homoarginyl residue at position 8, with no arginyl substituent at position 6.
Inventors
- 👤 John J. Nestor, Jr.
- 👤 Brian H. Vickery
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-11-03 06:07
CPC Classifications
C; C07; C07K; C07K7/00; C07K7/04; C07K7/06; C07K7/23; A; A61; A61K; A61K38/00; Y; Y10; Y10S; Y10S930/00; Y10S930/01; Y10S930/13
Claims Analysis
Total Claims: 42
Claim 1
Independent Claim
250 words
A compound of the formula ##STR6## or a pharmaceutically acceptable salt thereof, wherein: A is an amino acyl residue selected from the group consisting of either the D- or the L-isomer of: N-Ac-D,L-Δ 3 ,4 -prolyl, N-Ac-D,L-prolyl, N-Ac-D,L-phenylalanyl, N-Ac-D,L-p-chlorophenylalanyl, N-Ac-D,L,-p-fluorophenylalanyl, N-Ac-3-(1-naphthyl)-D,L-alanyl, N-Ac-3-(2-naphthyl)-D,L-alanyl, and N-Ac-3-(2,4,6-trimethylphenyl)-D,L-alanyl; B is an amino acyl residue selected from the group consisting of D-phenylalanyl, D-p-chlorophenylalanyl, D-p-fluorophenylalanyl, D-p-nitrophenylalanyl, 2,2-diphenylglycyl, D-α-methyl-p-chlorophenylalanyl and 3-(2-naphthyl)-D-alanyl; C is an amino acyl residue selected from the group consisting of D-tryptophanyl, D-phenylalanyl, 3-(3-pyridyl)-D-alanyl, and 3-(2-naphthyl)-D-alanyl; D is an amino acyl residue selected from the group consisting of L-phenylalanyl, L-tyrosyl, and 3-(3-pyridyl)-alanyl, arginyl, or G; E is 3-(2-naphthyl)-D-alanyl, 3-(3-pyridyl)-D-alanyl, D-tyrosyl, D-tryptophanyl, D-nicotinyl-lysyl, pyridylacetyl-lysyl, D-Glu(AA) or G; F is an amino acyl residue selected from the group consisting of L-leucyl, L-norleucyl, L-phenylalanyl, L-tryptophanyl, and 3-(2-naphthyl)-L-alanyl; G is an amino acyl residue selected from the group consisting of the radicals represented by the following structural formulas: ##STR7## wherein n is 1 to 5; R 1 is alkyl of 1 to 6 carbon atoms or fluoroalkyl; R 2 is hydrogen or R 1 ; or R 1 --HN--C═NR 2 is a ring represented by the following structure formulas: ##STR8## wherein m is 1 to 4; A is hydrogen or alkyl of 1 to 6 carbon atoms; and X is halo or A; and ##STR9## wherein R 3 is hydrogen, alkyl of 1 to 6 carbon atoms, phenyl or phenylloweralkyl; and J is D-alaninamide; D-leucinamide; glycinamide; or --NHR 4 wherein R 4 is lower alkyl or NHCONH 2 .
Claim 2
Dependent Claim
250 words
A compound of the formula ##STR6## or a pharmaceutically acceptable salt thereof, wherein: A is an amino acyl residue selected from the group consisting of either the D- or the L-isomer of: N-Ac-D,L-Δ 3 ,4 -prolyl, N-Ac-D,L-prolyl, N-Ac-D,L-phenylalanyl, N-Ac-D,L-p-chlorophenylalanyl, N-Ac-D,L,-p-fluorophenylalanyl, N-Ac-3-(1-naphthyl)-D,L-alanyl, N-Ac-3-(2-naphthyl)-D,L-alanyl, and N-Ac-3-(2,4,6-trimethylphenyl)-D,L-alanyl; B is an amino acyl residue selected from the group consisting of D-phenylalanyl, D-p-chlorophenylalanyl, D-p-fluorophenylalanyl, D-p-nitrophenylalanyl, 2,2-diphenylglycyl, D-α-methyl-p-chlorophenylalanyl and 3-(2-naphthyl)-D-alanyl; C is an amino acyl residue selected from the group consisting of D-tryptophanyl, D-phenylalanyl, 3-(3-pyridyl)-D-alanyl, and 3-(2-naphthyl)-D-alanyl; D is an amino acyl residue selected from the group consisting of L-phenylalanyl, L-tyrosyl, and 3-(3-pyridyl)-alanyl, arginyl, or G; E is 3-(2-naphthyl)-D-alanyl, 3-(3-pyridyl)-D-alanyl, D-tyrosyl, D-tryptophanyl, D-nicotinyl-lysyl, pyridylacetyl-lysyl, D-Glu(AA) or G; F is an amino acyl residue selected from the group consisting of L-leucyl, L-norleucyl, L-phenylalanyl, L-tryptophanyl, and 3-(2-naphthyl)-L-alanyl; G is an amino acyl residue selected from the group consisting of the radicals represented by the following structural formulas: ##STR7## wherein n is 1 to 5; R 1 is alkyl of 1 to 6 carbon atoms or fluoroalkyl; R 2 is hydrogen or R 1 ; or R 1 --HN--C═NR 2 is a ring represented by the following structure formulas: ##STR8## wherein m is 1 to 4; A is hydrogen or alkyl of 1 to 6 carbon atoms; and X is halo or A; and ##STR9## wherein R 3 is hydrogen, alkyl of 1 to 6 carbon atoms, phenyl or phenylloweralkyl; and J is D-alaninamide; D-leucinamide; glycinamide; or --NHR 4 wherein R 4 is lower alkyl or NHCONH 2 .
Claim 3
Dependent Claim
70 words
A compound of claim 2 wherein: A is N-Ac-D-Nal(2) or N-Ac-D-pCl-Phe; B is D-pCl-Phe or D-pF-Phe; C is D-Trp, D-Nal(2) or D-Pal(3); D is Pal(3), Tyr, Arg, Deh, Mbh, Bth or Pha; E is D-Trp, D-Tyr, D-Nal(2), D-Pal(3), D-Deh, D-Bth, D-Mbh or D-Pha; F is Leu or Phe; G is Deh, Bth, Mbh, or Pha; and J is D-AlaNH 2 or GlyNH 2 ; or a pharmaceutically acceptable salt thereof.
Claim 4
Dependent Claim
41 words
A compound of claim 2 wherein: A is N-Ac-D-Nal(2); B is D-pCl-Phe; C is D-Trp or D-Pal(3); D is Tyr, Arg, Deh, Mbh, Bth or Pha; F is Leu; and J is D-AlaNH 2 ; or a pharmaceutically acceptable salt thereof.
Claim 5
Dependent Claim
17 words
A compound of claim 3 wherein G is Deh or Bth or a pharmaceutically acceptable salt thereof.
Claim 6
Dependent Claim
15 words
A compound of claim 4 wherein G is Bth or a pharmaceutically acceptable salt thereof.
Claim 7
Dependent Claim
21 words
A compound of claim 3 which is N-Ac-D-Nal(2)-D-pCl-Phe-C-Ser-Tyr-E-Leu-G-Pro-D-AlaNH 2 wherein E is D-Pal(3) or D-Trp; or a pharmaceutically acceptable salt thereof.
Claim 8
Dependent Claim
18 words
A compound of claim 6 wherein C and E are the same or a pharmaceutically acceptable salt thereof.
Claim 9
Dependent Claim
24 words
A compound of claim 3 which is N-Ac-D-Nal(2)-D-pCl-Phe-C-Ser-Tyr-E-Leu-G-Pro-D-AlaNH 2 , wherein E is D-Deh, D-Bth, D-Mbh or D-Pha; or a pharmaceutically acceptable salt thereof.
Claim 10
Dependent Claim
24 words
A compound of claim 3 which is N-Ac-D-Nal(2)-D-pCl-Phe-C-Ser-Arg-E-Leu-G-Pro-D-AlaNH 2 , wherein E is D-Trp, D-Pal(3), D-Nal(2), or D-Tyr; or a pharmaceutically acceptable salt thereof.
Claim 11
Dependent Claim
15 words
A compound of claim 9 wherein E is D-Tyr; or a pharmaceutically acceptable salt thereof.
Claim 12
Dependent Claim
17 words
A compound of claim 9 wherein E is D-Trp or D-Pal(3); or a pharmaceutically acceptable salt thereof.
Claim 13
Dependent Claim
18 words
A compound of claim 11 wherein C and E are the same; or a pharmaceutically acceptable salt thereof.
Claim 14
Dependent Claim
32 words
A compound of claim 3 which is N-Ac-D-Nal(2)-D-pCl-Phe-C-Ser-D-E-Leu-G-Pro-D-AlaNH 2 , wherein D is Deh, Bth, Mbh or Pha, and E is D-Tyr, D-Nal(2), D-Trp or D-Pal(3); or a pharmaceutically acceptable salt thereof.
Claim 15
Dependent Claim
17 words
A compound of claim 13 wherein E is D-Tyr or D-Pal(3) or a pharmaceutically acceptable salt thereof.
Claim 16
Dependent Claim
23 words
A compound of claim 3 which is N-Ac-D-Nal(2)-D-pCl-Phe-D-Trp-Ser-Tyr-E-Leu-G-Pro-D-AlaNH 2 , wherein E is D-Trp, D-Tyr, or D-Nal(2); or a pharmaceutically acceptable salt thereof.
Claim 17
Dependent Claim
36 words
A compound of claim 3 which is N-Ac-D-Nal(2)-D-pCl-Phe-C-Ser-D-E-Leu-G-Pro-D-AlaNH 2 , wherein D and G are independently Deh, Bth, Mbh or Pha, and C and E are independently D-Trp or D-Pal(3); or a pharmaceutically acceptable salt thereof.
Claim 18
Dependent Claim
16 words
A compound of claim 3 which is N-Ac-D-Nal(2)-D-pCl-Phe-D-Pal(3)-Ser-Tyr-D-Pal(3)-Leu-G-Pro-D-AlaNH 2 ; or a pharmaceutically acceptable salt thereof.
Claim 19
Dependent Claim
42 words
A compound of claim 3 selected from the group consisting of: N-Ac-D-Nal(2)-D-pCl-Phe-D-Pal(3)-Ser-Tyr-D-Pal(3)-Leu-Deh-Pro-D-AlaNH 2 ; N-Ac-D-Nal(2)-D-pCl-Phe-D-Pal(3)-Ser-Tyr-D-Pal(3)-Leu-Bth-Pro-D-AlaNH 2 ; N-Ac-D-Nal(2)-D-pCl-Phe-D-Pal(3)-Ser-Tyr-D-Pal(3)-Leu-Mbh-Pro-D-AlaNH 2 ; N-Ac-D-Nal(2)-D-pCl-Phe-D-Pal(3)-Ser-Tyr-D-Pal(3)-Leu-Pha-Pro-D-AlaNH 2 ; N-Ac-D-Nal(2)-D-pCl-Phe-D-Trp-Ser-Tyr-D-Trp-Leu-Deh-Pro-D-AlaNH 2 ; N-Ac-D-Nal(2)-D-pCL-Phe-D-Trp-Ser-Tyr-D-Trp-Leu-Bth-Pro-D-AlaNH 2 ; N-Ac-D-Nal(2)-D-pCl-Phe-D-Trp-Ser-Tyr-D-Trp-Leu-Mbh-Pro-D-AlaNH 2 ; and N-Ac-D-Nal(2)-D-pCl-Phe-D-Trp-Ser-Tyr-D-Trp-Leu-Pha-Pro-D-AlaNH 2 ; or a pharmaceutically acceptable salt thereof.
Claim 20
Dependent Claim
42 words
A compound of claim 3 selected from the group consisting of: N-Ac-D-Nal(2)-D-pCl-Phe-D-Trp-Ser-Tyr-D-Deh-Leu-Deh-Pro-D-AlaNH 2 ; N-Ac-D-Nal(2)-D-pCl-Phe-D-Trp-Ser-Tyr-D-Mbh-Leu-Mbh-Pro-D-AlaNH 2 ; N-Ac-D-Nal(2)-D-pCl-Phe-D-Trp-Ser-Tyr-D-Bth-Leu-Bth-Pro-D-AlaNH 2 ; N-Ac-D-Nal(2)-D-pCL-Phe-D-Trp-Ser-Tyr-D-Pha-Leu-Pha-Pro-D-AlaNH 2 ; N-Ac-D-Nal(2)-D-pCl-Phe-D-Pal(3)-Ser-Tyr-D-Deh-Leu-Deh-Pro-D-AlaNH 2 ; N-Ac-D-Nal(2)-D-pCl-Phe-D-Pal(3)-Ser-Tyr-D-Mbh-Leu-Mbh-Pro-D-AlaNH 2 ; N-Ac-D-Nal(2)-D-pCl-Phe-D-Pal(3)-Ser-Tyr-D-Bth-Leu-Bth-Pro-D-AlaNH 2 ; and N-Ac-D-Nal(2)-D-pCl-Phe-D-Pal(3)-Ser-Tyr-D-Pha-Leu-Pha-Pro-D-AlaNH 2 ; or a pharmaceutically acceptable salt thereof.
Claim 21
Dependent Claim
66 words
A compound of claim 3 selected from the group consisting of: N-Ac-D-Nal(2)-D-pCl-Phe-D-Trp-Ser-Arg-D-Trp-Leu-Deh-Pro-D-AlaNH 2 ; N-Ac-D-Nal(2)-D-pCl-Phe-D-Trp-Ser-Arg-D-Trp-Leu-Bth-Pro-D-AlaNH 2 ; N-Ac-D-Nal(2)-D-pCl-Phe-D-Trp-Ser-Arg-D-Trp-Leu-Mbh-Pro-D-AlaNH 2 ; N-Ac-D-Nal(2)-D-pCl-Phe-D-Trp-Ser-Arg-D-Trp-Leu-Pha-Pro-D-AlaNH 2 ; N-Ac-D-Nal(2)-D-pCl-Phe-D-Pal(3)-Ser-Arg-D-Pal(3)-Leu-Bth-Pro-D-AlaNH 2 ; N-Ac-D-Nal(2)-D-pCl-Phe-D-Pal(3)-Ser-Arg-D-Pal(3)-Leu-Mbh-Pro-D-AlaNH 2 ; N-Ac-D-Nal(2)-D-pCl-Phe-D-Pal(3)-Ser-Arg-D-Pal(3)-Leu-Deh-Pro-D-AlaNH 2 ; N-Ac-D-Nal(2)-D-pCl-Phe-D-Pal(3)-Ser-Arg-D-Pal(3)-Leu-Pha-Pro-D-AlaNH 2 ; N-Ac-D-Nal(2)-D-pCl-Phe-D-Trp-Ser-Arg-D-Tyr-Leu-Deh-Pro-D-AlaNH 2 ; N-Ac-D-Nal(2)-D-pCl-Phe-D-Trp-Ser-Arg-D-Tyr-Leu-Bth-Pro-D-AlaNH 2 ; N-Ac-D-Nal(2)-D-pCl-Phe-D-Trp-Ser-Arg-D-Tyr-Leu-Mbh-Pro-D-AlaNH 2 ; N-Ac-D-Nal(2)-D-pCl-Phe-D-Trp-Ser-Arg-D-Tyr-Leu-Pha-Pro-D-AlaNH 2 ; N-Ac-D-Nal(2)-D-pCl-Phe-D-Pal(3)-Ser-Arg-D-Tyr-Leu-Bth-Pro-D-AlaNH 2 ; N-Ac-D-Nal(2)-D-pCl-Phe-D-Pal(3)-Ser-Arg-D-Tyr-Leu-Mbh-Pro-D-AlaNH 2 ; N-Ac-D-Nal(2)-D-pCl-Phe-D-Pal(3)-Ser-Arg-D-Tyr-Leu-Deh-Pro-D-AlaNH 2 ; N-Ac-D-Nal(2)-D-pCl-Phe-D-Pal(3)-Ser-Arg-D-Tyr-Leu-Pha-Pro-D-AlaNH 2 ; and or a pharmaceutically acceptable salt thereof.
Claim 22
Dependent Claim
74 words
A compound of claim 3 selected from the group consisting of: N-Ac-D-Nal(2)-D-pCl-Phe-D-Trp-Ser-Deh-D-Tyr-Leu-Deh-Pro-D-AlaNH 2 ; N-Ac-D-Nal(2)-D-pCl-Phe-D-Trp-Ser-Mbh-D-Tyr-Leu-Mbh-Pro-D-AlaNH 2 ; N-Ac-D-Nal(2)-D-pCl-Phe-D-Trp-Ser-Bth-D-Tyr-Leu-Bth-Pro-D-AlaNH 2 ; N-Ac-D-Nal(2)-D-pCl-Phe-D-Trp-Ser-Pha-D-Tyr-Leu-Pha-Pro-D-AlaNH 2 ; N-Ac-D-Nal(2)-D-pCl-Phe-D-Trp-Ser-Deh-D-Trp-Leu-Deh-Pro-D-AlaNH 2 ; N-Ac-D-Nal(2)-D-pCl-Phe-D-Trp-Ser-Mbh-D-Trp-Leu-Mbh-Pro-D-AlaNH 2 ; N-Ac-D-Nal(2)-D-pCl-Phe-D-Trp-Ser-Bth-D-Trp-Leu-Bth-Pro-D-AlaNH 2 ; N-Ac-D-Nal(2)-D-pCl-Phe-D-Trp-Ser-Pha-D-Trp-Leu-Pha-Pro-D-AlaNH 2 ; N-Ac-D-Nal(2)-D-pCl-Phe-D-Pal(3)-Ser-Deh-D-Pal(3)-Leu-Deh-Pro-D-AlaNH 2 ; N-Ac-D-Nal(2)-D-pCl-Phe-D-Pal(3)-Ser-Mbh-D-Pal(3)-Leu-Mbh-Pro-D-AlaNH 2 ; N-Ac-D-Nal(2)-D-pCl-Phe-D-Pal(3)-Ser-Bth-D-Pal(3)-Leu-Bth-Pro-D-AlaNH 2 ; N-Ac-D-Nal(2)-D-pCl-Phe-D-Pal(3)-Ser-Pha-D-Pal(3)-Leu-Pha-Pro-D-AlaNH 2 ; N-Ac-D-Nal(2)-D-pCl-Phe-D-Trp-Ser-Deh-D-Nal(2)-Leu-Deh-Pro-D-AlaNH 2 ; N-Ac-D-Nal(2)-D-pCl-Phe-D-Trp-Ser-Mbh-D-Nal(2)-Leu-Mbh-Pro-D-AlaNH 2 ; N-Ac-D-Nal(2)-D-pCl-Phe-D-Trp-Ser-Bth-D-Nal(2)-Leu-Bth-Pro-D-AlaNH 2 ; N-Ac-D-Nal(2)-D-pCl-Phe-D-Trp-Ser-Pha-D-Nal(2)-Leu-Pha-Pro-D-AlaNH 2 ; N-Ac-D-Nal(2)-D-pCl-Phe-D-Pal(3)-Ser-Pal(3)-D-Pal(3)-Leu-Deh-Pro-D-AlaNH.sub.2 ; N-Ac-D-Nal(2)-D-pCl-Phe-D-Pal(3)-Ser-Pal(3)-D-Pal(3)-Leu-Bth-Pro-D-AlaNH.sub.2 ; N-Ac-D-Nal(2)-D-pCl-Phe-D-Pal(3)-Ser-Pal(3)-D-Pal(3)-Leu-Pha-Pro-D-AlaNH.sub.2 ; and N-Ac-D-Nal(2)-D-pCl-Phe-D-Pal(3)-Ser-Pal(3)-D-Pal(3)-Leu-Mbh-Pro-D-AlaNH.sub.2 ; or a pharmaceutically acceptable salt thereof.
Claim 23
Dependent Claim
65 words
A compound of claim 3 selected from the group consisting of: N-Ac-D-Nal(2)-D-pCl-Phe-D-Pal(3)-Ser-Tyr-D-Pal(3)-Leu-Deh-Pro-D-AlaNH 2 ; N-Ac-D-Nal(2)-D-pCl-Phe-D-Pal(3)-Ser-Mbh-D-Pal(3)-Leu-Mbh-Pro-D-AlaNH 2 ; N-Ac-D-Nal(2)-D-pCl-Phe-D-Pal(3)-Ser-Pal(3)-D-Pal(3)-Leu-Bth-Pro-D-AlaNH.sub.2 ; N-Ac-D-Nal(2)-D-pCl-Phe-D-Pal(3)-Ser-Arg-D-Pal(3)-Leu-Deh-Pro-D-AlaNH 2 ; N-Ac-D-Nal(2)-D-pCl-Phe-D-Pal(3)-Ser-Tyr-D-Pal(3)-Leu-Bth-Pro-D-AlaNH 2 ; N-Ac-D-Nal(2)-D-pCl-Phe-D-Pal(3)-Ser-Tyr-D-Pal(3)-Leu-Mbh-Pro-D-AlaNH 2 ; N-Ac-D-Nal(2)-D-pCl-Phe-D-Pal(3)-Ser-Tyr-D-Pal(3)-Leu-Pha-Pro-D-AlaNH 2 ; N-Ac-D-Nal(2)-D-pCl-Phe-D-Trp-Ser-Tyr-D-Trp-Leu-Bth-Pro-D-AlaNH 2 ; N-Ac-D-Nal(2)-D-pCl-Phe-D-Trp-Ser-Arg-D-Trp-Leu-Deh-Pro-D-AlaNH 2 ; N-Ac-D-Nal(2)-D-pCl-Phe-D-Trp-Ser-Arg-D-Trp-Leu-Bth-Pro-D-AlaNH 2 ; N-Ac-D-Nal(2)-D-pCl-Phe-D-Trp-Ser-Arg-D-Trp-Leu-Pha-Pro-D-AlaNH 2 ; N-Ac-D-Nal(2)-D-pCl-Phe-D-Pal(3)-Ser-Arg-D-Pal(3)-Leu-Pha-Pro-D-AlaNH 2 ; N-Ac-D-Nal(2)-D-pCl-Phe-D-Trp-Ser-Tyr-D-Bth-Leu-Bth-Pro-D-AlaNH 2 ; N-Ac-D-Nal(2)-D-pCl-Phe-D-Trp-Ser-Tyr-D-Phe-Leu-Pha-Pro-D-AlaNH 2 ; N-Ac-D-Nal(2)-D-pCl-Phe-D-Pal(3)-Ser-Tyr-D-Deh-Leu-Deh-Pro-D-AlaNH 2 ; and N-Ac-D-Nal(2)-D-pCl-Phe-D-Pal(3)-Ser-Tyr-D-Bth-Leu-Bth-Pro-D-AlaNH 2 ; or a pharmaceutically acceptable salt thereof.
Claim 24
Dependent Claim
16 words
A compound of claim 3 which is: N-Ac-D-Nal(2)-D-pCl-Phe-D-Pal(3)-Ser-Tyr-D-Pal(3)-Leu-Deh-Pro-D-AlaNH 2 ; or a pharmaceutically acceptable salt thereof.
Claim 25
Dependent Claim
16 words
A compound of claim 3 which is: N-Ac-D-Nal(2)-D-pCl-Phe-D-Pal(3)-Ser-Tyr-D-Pal(3)-Leu-Bth-Pro-D-AlaNH 2 ; or a pharmaceutically acceptable salt thereof.
Claim 26
Dependent Claim
16 words
A compound of claim 3 which is: N-Ac-D-Nal(2)-D-pCl-Phe-D-Pal(3)-Ser-Tyr-D-Pal(3)-Leu-Mbh-Pro-D-AlaNH 2 ; or a pharmaceutically acceptable salt thereof.
Claim 27
Dependent Claim
16 words
A compound of claim 3 which is: N-Ac-D-Nal(2)-D-pCl-Phe-D-Pal(2)-Ser-Tyr-D-Pal(3)-Leu-Pha-Pro-D-AlaNH 2 ; or a pharmaceutically acceptable salt thereof.
Claim 28
Dependent Claim
16 words
A compound of claim 3 which is: N-Ac-D-Nal(2)-D-pCl-Phe-D-Trp-Ser-Tyr-D-Trp-Leu-Bth-Pro-D-AlaNH 2 ; or a pharmaceutically acceptable salt thereof.
Claim 29
Dependent Claim
16 words
A compound of claim 3 which is: N-Ac-D-Nal(2)-D-pCl-Phe-D-Trp-Ser-Arg-D-Trp-Leu-Bth-Pro-D-AlaNH 2 ; or a pharmaceutically acceptable salt thereof.
Claim 30
Dependent Claim
16 words
A compound of claim 3 which is: N-Ac-D-Nal(2)-D-pCl-Phe-D-Trp-Ser-Arg-D-Trp-Leu-Pha-Pro-D-AlaNH 2 ; or a pharmaceutically acceptable salt thereof.
Claim 31
Dependent Claim
16 words
A compound of claim 3 which is: N-Ac-D-Nal(2)-D-pCl-Phe-D-Pal(3)-Ser-Arg-D-Pal(3)-Leu-Bth-Pro-D-AlaNH 2 ; or a pharmaceutically acceptable salt thereof.
Claim 32
Dependent Claim
16 words
A compound of claim 3 which is: N-Ac-D-Nal(2)-D-pCl-Phe-D-Pal(3)-Ser-Arg-D-Pal(3)-Leu-Pha-Pro-D-AlaNH 2 ; or a pharmaceutically acceptable salt thereof.
Claim 33
Dependent Claim
16 words
A compound of claim 3 which is: N-Ac-D-Nal(2)-D-pCl-Phe-D-Pal(3)-Ser-Mbh-D-Pal(3)-Leu-Mbh-Pro-D-AlaNH 2 ; or a pharmaceutically acceptable salt thereof.
Claim 34
Dependent Claim
15 words
A compound of claim 3 which is: N-Ac-D-Nal(2)-D-pCl-Phe-D-Pal(3)-Ser-Pal(3)-D-Pal(3)-Leu-Bth-Pro-D-AlaNH.sub.2 ; or a pharmaceutically acceptable salt thereof.
Claim 35
Dependent Claim
16 words
A compound of claim 3 which is: N-Ac-D-Nal(2)-D-pCl-Phe-D-Pal(3)-Ser-Arg-D-Pal(3)-Leu-Deh-Pro-D-AlaNH 2 ; or a pharmaceutically acceptable salt thereof.
Claim 36
Dependent Claim
85 words
A pharmaceutical composition for inhibiting ovulation in a mammalian female subject; preventing ovarian hyperstimulation in response to exogenous gonadotropins, treating premenstrual syndrome, or treating endometriosis in a female human subject; for treating prostatic hypertrophy or inhibiting spermatogenesis in a male mammalian subject; or for treating precocious puberty in a human subject; or interrupting heat in a female animal; or terminating pregnancy in a female mammalian subject; comprising an effective amount of the compound of claim 1 in admixture with at least one pharmaceutically acceptable excipient.
Claim 37
Dependent Claim
21 words
A compound of claim 3 which is N-Ac-D-Nal(2)-D-pCl-Phe-D-Pal(3)-Ser-Bth-D-Tyr-Leu-Bth-Pro-D-Ala-NH 2 ; or an optical isomer thereof; or a pharmaceutically acceptable salt thereof.
Claim 38
Dependent Claim
21 words
The compound of claim 3 which is N-Ac-D-Nal(2)-D-pCl-Phe-D-Trp-Ser-Tyr-D-Bth-Leu-Bth-Pro-D-AlaNH 2 ; or an optical isomer thereof; or a pharmaceutically acceptable salt thereof.
Claim 39
Dependent Claim
20 words
The compound of claim 3 which is N-Ac-D-Nal(2)-D-pCl-Phe-D-Trp-Ser-Tyr-D-Pha-Leu-Pha-Pro-D-AlaNH 2 or an optical isomer thereof; or a pharmaceutically acceptable salt thereof.
Claim 40
Dependent Claim
21 words
The compound of claim 3 which is N-Ac-D-Nal(2)-D-pCl-Phe-D-Pal(3)-Ser-Tyr-D-Deh-Leu-Deh-Pro-D-AlaNH 2 ; or an optical isomer thereof; or a pharmaceutically acceptable salt thereof.
Claim 41
Dependent Claim
21 words
The compound of claim 3 which is N-Ac-D-Nal(2)-D-pCl-Phe-D-Pal(3)-Ser-Tyr-D-Bth-Leu-Bth-Pro-D-AlaNH 2 ; or an optical isomer thereof; or a pharmaceutically acceptable salt thereof.
Claim 42
Dependent Claim
21 words
The compound of claim 3 which is N-Ac-D-Nal(2)-D-pCl-Phe-D-Pal(3)-Ser-Mbh-D-Pal(3)-Leu-Mbh-Pro-D-AlaNH 2 ; or an optical isomer thereof; or a pharmaceutically acceptable salt thereof.
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| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1992-01-31 | 1992-08-01 | 1993-01-31 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1996-01-31 | 1996-08-01 | 1997-01-31 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 2000-01-31 | 2000-08-01 | 2001-01-31 | $7700.00 | Window Closed / Lapsed |