Back to results
US 5,516,759 AGranted
LHRH antagonists having lactam groups at the N-terminus
AssigneeTap Holdings Inc.
InventorsRolf E. Swenson, Fortuna Haviv, Nicholas A. Mort
Life of this patent
Estimating the term…
Abstract
Peptides possessing LHRH antagonistic activity, and useful for the controlling the release of LHRH in mammals are decapeptide analogues of LHRH having a lactam group at the N-terminus of the formula ##STR1## where n is 1, 2, or 3 and R.sup.1 is selected from the group consisting of hydrogen, benzyl, 4-chlorobenzyl, 2-methylnaphth-1-yl, 1-methylnaphth-2-yl, and quinolin-3-ylmethyl.
Claims6
A peptide of the formula:
- X--B--C--D--E--F--G--H--I--J--NH.sub.2
- or a pharmaceutically acceptable salt thereof
- wherein
- X is a lactam group of the formula ##STR21## wherein n is 1, 2, or 3 and R.sup.1 is selected from the group consisting of
- hydrogen,
- benzyl,
- 4-chlorobenzyl,
- 2-methylnaphth-1-yl,
- 1-methylnaphth-2-yl, and
- quinolin-3-ylmethyl;
- B is an aminoacyl residue selected from the group consisting of
- D-phenylalanyl,
- D-3-(4-chlorophenyl)alanyl,
- D-3-(4-fluorophenyl)alanyl, and
- D-3-(naphth-2-yl)alanyl;
- C is an aminoacyl residue selected from the group consisting of
- D-3-pyrid-3-yl)alanyl,
- glycyl,
- D-3-(naphth-1-yl)alanyl,
- D-alanyl, and
- D-tryptophyl;
- D is an aminoacyl residue selected from the group consisting of
- L-seryl,
- N.sup..alpha. -methyl-L-seryl,
- glycyl, and
- L-threonyl;
- E is an aminioacyl residue selected from the group consisting of
- L-tyrosyl,
- N.sup..alpha. -methyl-L-tyrosyl,
- N.sup..alpha. -methyl-L-phenylalanyl,
- (N.sup..epsilon. -nicotinyl)-L-lysyl,
- (N.sup..epsilon. -picolinyl)-L-lysyl,
- L-3-(4-((3-amino-1H-1,2,4-triazol-5-yl)amino)phenyl)alanyl, and
- N.sup.+ -methyl-L-3-(4-((3-amino-1H-1,2,4-triazol-5-yl)amino)phenyl)alanyl;
- F is an aminoacyl residue selected from the group consisting of
- (N.sup..epsilon. -nicotinyl)-D-lysyl,
- (N.sup..epsilon. -glycyl)-D-lysyl,
- (N.sup..epsilon. -nicotinylazaglycyl)-D-lysyl,
- (N.sup..epsilon. -furo-2-ylazaglycyl)-D-lysyl,
- D-3-(4-((3-amino-1H-1,2,4-triazol-5-yl)amino)phenyl)alanyl,
- D-lysyl(N-epsilon glycyl nicotinyl),
- D-lysyl(N-epsilon furo-2-yl),
- D-lysyl(N-epsilon glycyl furo-2-yl),
- (N.sup..epsilon. -shikimyl)-D-lysyl,
- (N.sup..epsilon. -shikimylglycyl)-D-lysyl,
- D-citrullyl,
- D-homocitrullyl,
- D-arginyl,
- D-homoarginyl,
- (N.sup.g,N.sup.g -diethyl)-D-homoarginyl, and
- (N.sup..epsilon. -pyrazinyl)-D-lysyl;
- G is an aminoacyl residue selected from the group consisting of
- L-leucyl,
- L-isoleucyl,
- N.sup..alpha. -methyl-L-leucyl,
- tert-butyl-L-glycyl, and
- L-valyl;
- H is an aminoacyl residue selected from the group consisting of
- L-arginyl,
- L-homoarginyl,
- (N.sup..epsilon. -isopropyl)-L-lysyl, and
- (N.sup.g,N.sup.g -diethyl)-L-homoarginyl;
- I is an aminoacyl residue selected from the group consisting of
- L-prolyl and
- N.sup..alpha. -methyl-L-alanyl;
- and
- J is an aminoacyl residue selected from the group consisting of
- glycyl,
- D-alanyl, and
- sarcosyl.
67 more elements
A peptide or pharmaceutically acceptable salt thereof having the formula:
- X--B--D3Pal--Ser--E--F--G--H--Pro--Ala--NH.sub.2
- wherein
- X is selected from the group consisting of
- 2-(N-2'-pyrrolidinonyl)-2-(R)-(2-naphthylmethyl)acetyl,
- and 2-(N-2'-piperidinonyl)-2-(R)-(2-naphthylmethyl)acetyl;
- acetyl;
- B is an aminoacyl residue selected from the group consisting of
- D-3-(4-chlorophenyl)alanyl, and
- D-3-(4-fluorophenyl)alanyl;
- E is an aminoacyl residue selected from the group consisting of
- L-tyrosyl,
- L-3-(4-((3-amino-1H-1,2,4-triazol-5-yl)amino)phenyl)alanyl,
- N.sup..alpha. -methyl-L-tyrosyl, and
- N.sup..alpha. -methyl-L-3-(4-((3-amino-1H-1,2,4-triazol-5-yl)amino)phenyl)alanyl;
- F is an aminoacyl residue selected from the group consisting of
- D-citrullyl,
- D-homocitrullyl,
- D-lysyl(N-epsilon nicotinyl),
- D-lysyl(N-epsilon glycyl nicotinyl),
- D-lysyl(N-epsilon azaglycyl nicotinyl),
- D-lysyl(N-epsilon shikimyl),
- D-lysyl(N-epsilon glycyl shikimyl),
- D-lysyl(N-epsilon furo-2-yl),
- D-lysyl(N-epsilon glycyl furo-2-yl),
- D-lysyl(N-epsilon azaglycyl furo-2-yl), and
- D-3-(4-((3-amino-1H-1,2,4-triazol-5-yl)amino)phenyl)alanyl;
- G is an aminoacyl residue selected from the group consisting of
- L-leucyl, and
- N.sup..alpha. -methyl-L-leucyl;
- and
- H is an aminoacyl residue selected from the group consisting of
- L-arginyl,
- L-homoarginyl,
- L-lysyl(N-epsilon isopropyl), and,
- L-2-amino-6-N.sup.g,N.sup.g -diethyl-guanidinohexanoyl.
32 more elements
Dependencies are inferred from the claim text.