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US 5,210,075 AGranted
Interleukin 6 antagonist peptides
AssigneeTanabe Seiyaku Co., Ltd.
InventorsWolfgang Scholz, Shiu-Lang Chiang, Gobi Nagarajan, Thomas J. Lobl
Life of this patent
Estimating the term…
Abstract
Peptides and derivatives useful as antagonists to interleukin 6, and uses for the same, are disclosed.
Claims15
A peptide of the formula
- X.sup.2 --(X.sup.1 --)7--8--9--10--11--12--14(--Y.sup.1)--Y.sup.2 (II)
- and pharmaceutically acceptable salts thereof, wherein
- 7 is selected from L;
- I and A;
- and V, Nle, Sar, .beta.-Ala and Aib;
- 8 is selected from A;
- L and I;
- and V, Nle, Sar, .beta.-Ala and G;
- 9 is selected from E;
- pyro-Glu;
- and D, S, T, Y, .beta.-Asp and 3-Glu;
- 10 is selected from N;
- Q, M, W and F;
- and Y;
- 11 is selected from N;
- Q, M, W and F;
- and Y;
- 12 is selected from L;
- I and A;
- and V, Nle, Sar, .beta.-Ala and Aib;
- 13 is selected from N;
- Q, M, W and F;
- and Y;
- and
- 14 is selected from L;
- I and A;
- and V, Nle, Sar, .beta.-Ala and Aib;
- X.sup.1 is optional and, where present, is selected from ##STR46## wherein 1is selected from E;
- pyro-Glu;
- and D, S, T, Y, .beta.-Asp and 3-Glu;
- 2 is selected from S;
- A and M;
- and T, HomoSer and Y;
- 3 is selected from S;
- A and M;
- and T, HomoSer and Y;
- 4 is selected from K;
- and R, Orn, HomoArg and H;
- 5 is selected from E;
- G and pyro-Glu;
- and D, S, T, Y, .beta.-Asp and 3-Glu;
- 6 is selected from A;
- L and I;
- and V, Nle, Sar, .beta.-Ala and G;
- wherein one or more D-amino acids may be employed among residues 1 to 6;
- Y.sup.1 is optional and, where present, is selected from ##STR47## wherein 15is selected from P;
- L and I;
- and V, Aib, hydroxy-Pro and HomoPro;
- 16 is selected from K;
- and R, Orn, HomoArg and H;
- 17 is selected from M;
- W, F and Q;
- and N, Y, H, .alpha.-naphthylalanine and .beta.-naphthylalanine;
- 18 is selected from A;
- L and I;
- and V, Nle, Sar, .beta.-Ala and G;
- 19 is selected from E;
- pyro-Glu;
- and D, S, T, Y, .beta.-Asp and 3-Glu;
- 20 is selected from K;
- and R, Orn, HomoArg and H;
- and
- wherein one or more D-amino acids may be employed among residues 15 to 20;
- X.sup.2 is a N.sup..alpha. -substituent selected from hydrogen, R'CO-- and R'--;
- Y.sup.2 is a carboxyl-terminal substituent selected from hydroxyl, --NH.sub.2, --NHR', --NR'.sub.2, --OR' and --NHNH.sub.2 ;
- and
- wherein each R' is individually a pharmaceutically suitable substituent group.
64 more elements
A peptide of the formula
- X.sup.c --(X.sup.1 --)7--8--9--10--11--12--13--14(--Y.sup.1)--Y.sup.c
- and pharmaceutically acceptable salts thereof, wherein
- 7 is selected from L;
- I and A;
- and V, Nle, Sar, .beta.-Ala and Aib;
- 8 is selected from A;
- L and I;
- and V, Nle, Sar, .beta.-Ala and G;
- 9 is selected from E;
- pyro-Glu;
- and D, S, T, Y, .beta.-Asp and 3-Glu;
- 10 is selected from N;
- Q, M, W and F;
- and Y;
- 11 is selected from N;
- Q, M, W and F;
- and Y;
- 12 is selected from L;
- I and A;
- and V, Nle, Sar, .beta.-Ala and Aib;
- 13is selected from N;
- Q, M, W and F;
- and Y;
- and
- 14 is selected from L;
- I and A;
- and V, Nle, Sar, .beta.-Ala and Aib;
- X.sup.1 is optional and, where present, is selected from ##STR49## wherein 1is selected from E;
- pyro-Glu;
- and D, S, T, Y, .beta.-Asp and 3-Glu;
- 2 is selected from S;
- A and M;
- and T, HomoSer and Y;
- 3 is selected from S;
- A and M;
- and T, HomoSer and Y;
- 4 is selected from K;
- and R, Orn, HomoArg and H;
- 5 is selected from E;
- G and pyro-Glu;
- and D, S, T, Y, .beta.-Asp and 3-Glu;
- 6 is selected from A;
- L and I;
- and V, Nle, Sar, .beta.-Ala and G;
- wherein one or more D-amino acids may be employed among residues 1 to 6;
- Y.sup.1 is optional and, where present, is selected from ##STR50## wherein 15is selected from P;
- L and I;
- and V, Aib, hydroxy-Pro and HomoPro
- 16 is selected from K;
- and R, Orn, HomoArg and H;
- 17 is selected from M;
- W, F and Q;
- and N, Y, H, .alpha.-naphthylalanine and .beta.-naphthylalanine;
- 18 is selected from A;
- L and I;
- and V, Nle, Sar, .beta.-Ala and G;
- 19 is selected from E;
- pyro-Glu;
- and D, S, T, Y, .beta.-Asp and 3-Glu;
- 20 is selected from K;
- and R, Orn, HomoArg and H;
- and wherein one or more D-amino acids may be employed among residues 15 to 20;
- and
- wherein one of X.sup.c and Y.sup.c is present and is a moiety suitable for coupling the peptide to another molecule.
61 more elements
A peptide of the formula
- X.sup.2 --(X.sup.1 --)3--4--5--6--7(--Y.sup.1)--Y.sup.2 (III)
- and pharmaceutically acceptable salts thereof, wherein
- 3 is selected from S;
- A and M;
- and T, HomoSer and Y;
- 4 is selected from K;
- and R, Orn, HomoArg and H;
- 5 is selected from E;
- G and pyro-Glu;
- and D, S, T, Y, .beta.-Asp and 3-Glu;
- 6 is selected from A;
- L and I;
- and V, Nle, Sar, .beta.-Ala and G;
- 7 is selected from L;
- I and A;
- and V, Nle, Sar, .beta.-Ala and Aib;
- wherein one or more D-amino acids may be employed among residues 3 to 7;
- X.sup.1 is optional and, where present, is selected from ##STR51## wherein 1is selected from E;
- pyro-Glu;
- and D, S, T, Y, .beta.-Asp and 3-Glu;
- and
- 2 is selected from S;
- A and M;
- and T, HomoSer and Y;
- Y.sup.1 is optional and, where present, is selected from ##STR52## wherein 8is selected from A;
- L and I;
- and V, Nle, Sar, .beta.-Ala and G;
- 9 is selected from E;
- pyro-Glu;
- and D, S, T, Y, .beta.-Asp and 3-Glu;
- 10 is selected from N;
- Q, M, W and F;
- and Y;
- and wherein
- X.sup.2 is a N.sup..alpha. -substituent selected from hydrogen, R'CO-- and R'--;
- Y.sup.2 is a carboxyl-terminal substituent selected from hydroxyl, --NH.sub.2, --NHR', --NR'.sub.2, --OR' and --NHNH.sub.2 ;
- and
- wherein each R' is individually a pharmaceutically suitable substituent group.
35 more elements
A peptide of the formula
- X.sup.2 --11--12--13--14--15--16(--Y.sup.1)--Y.sup.2 (IV)
- and pharmaceutically acceptable salts thereof, wherein
- 11 is selected from N;
- Q, M, W and F;
- and Y;
- 12is selected from L;
- I and A;
- and V, Nle, Sar, .beta.-Ala and Aib;
- 13 is selected from N;
- Q, M, W and F;
- and Y;
- 14 is selected from L;
- I and A;
- and V, Nle, Sar, .beta.-Ala and Aib;
- 15 is selected from P;
- L and I;
- and V, Aib, hydroxy-Pro and HomePro;
- 16 is selected from K;
- and R, Orn, HomoArg and H;
- wherein one or more D-amino acids may be employed among residues 15 to 16;
- Y.sup.1 is optional and, where present, is selected from ##STR53## wherein 17is selected from M;
- W, F and Q;
- and N, Y, H, .alpha.-naphthylalanine and .beta.-naphthylalanine;
- 18 is selected from A;
- L and I;
- and V, Nle, Sar, .beta.-Ala and G;
- 19 is selected from E;
- pyro-Glu;
- and D, S, T, Y, .beta.-Asp and 3-Glu;
- 20is selected from K;
- and R, Orn, HomoArg and H;
- and wherein one or more D-amino acids may be employed among residues 17 to 20;
- and wherein
- X.sup.2 is a N.sup..alpha. -substituent selected from hydrogen, R'CO-- and R'--;
- Y.sup.2 is a carboxyl-terminal substituent selected from hydroxyl, --NH.sub.2, --NHR', --NR'.sub.2, --OR' and --NHNH.sub.2 ;
- and
- wherein each R' is individually a pharmaceutically suitable substituent group.
34 more elements
Dependencies are inferred from the claim text.