Endothelin-antagonizing peptide
AssigneeKyowa Hakko Kogyo Co., Ltd.
InventorsKenji Shibata, Toshiyuki Suzawa, Motoo Yamasaki, Takeo Tanaka, Eiji Tsukuda, Koji Yamada, Tetsuji Ohno
Life of this patent
Estimating the term…
Abstract
Disclosed is a peptide compound represented by the following formula (I): R.sup.1 -R.sup.2 -R.sup.3 -R.sup.4 -R.sup.5 -R.sup.6 -R.sup.7 -R.sup.8 -R.sup.9 -R.sup.10 -R.sup.11 -R.sup.12 -Phe-R.sup.14 -R.sup.15 -R.sup.16 -R.sup.17 -R.sup.18 -Ile-R.sup.20 -Z SEQ. ID NO. 64, (I) wherein R.sup.1-12, R.sup.14-18, and R.sup.20 are as defined in the specification.
Claims9
A peptide compound represented by the following formula:
- R.sup.1 -R.sup.2 -R.sup.3 -R.sup.4 -R.sup.5 -R.sup.6 -R.sup.7 -R.sup.8 -R.sup.9 -R.sup.10 -R.sup.11 -R.sup.12 -Phe-R.sup.14 -R.sup.15 -R.sup.16 -R.sup.17 -R.sup.18 -Ile-R.sup.20 -Z SEQ ID NO. 64
- wherein R.sup.1 represents ##STR23## or hydrogen;
- R.sup.2 represents Asn, Asp, Phe, Tyr, Ser, or a single bond;
- R.sup.3 represents Trp, Ile, Pro, Ala, or a single bond;
- R.sup.4 represents His, Lys, Gly, Trp, Ala, or a single bond;
- R.sup.5 represents Gly, Thr, Trp, Val, or a single bond;
- R.sup.6 represents Gly, Thr, Asn, Tyr, Asp, or a single bond;
- R.sup.7 represents Ala, Ser, Asn, Asp, Tyr, Phe, or a single bond;
- R.sup.8 represents Pro, Ala, Arg, or a single bond;
- R.sup.9 represents ##STR24## or a single bond;
- R.sup.10 represents Trp or Ala;
- R.sup.11 represents Val, Pro, or a single bond;
- R.sup.12 represents Tyr or a single bond;
- R.sup.14 represents Ala, MeAla, Ser, or Cys;
- R.sup.15 represents His or Trp;
- R.sup.16 represents Leu or Nva;
- R.sup.17 represents Asp, Thr, Asn, Ser, Gly, or Glu;
- R.sup.18 represents Ile, Leu, Cha, Abu, Thi, Met, Tyr, MeLeu, MeIle, Phg, or Nle;
- R.sup.20 represents Trp, Phe, or Tyr;
- and
- Z represents hydroxy, lower alkoxy, or amino (wherein X.sup.1 and X.sup.3 each represent hydrogen, benzyloxycarbonyl, t-butyloxycarbonyl, 9-fluorenylmethyloxycarbonyl, or carboxy-substituted or unsubstituted lower alkanoyl;
- X.sup.2 represents hydrogen or acetamidomethyl;
- Y.sup.1 represents hydroxy or lower alkoxy;
- Y.sup.2 represents hydrogen, or X.sup.1 and Y.sup.1 or X.sup.2 and Y.sup.2 are combined together to form a single bond as X.sup.1 -Y.sup.1 or X.sup.2 -Y.sup.2 ;
- and Nva represents a norvaline residue, Cha represents a .beta.-cyclohexylalanine residue, Abu represents a 2-aminobutanoic acid residue, Thi represents a .beta.-(2-thienyl)alanine residue, Phg represents a phenylglycine residue, Nle represents a norleucine residue, MeAla represents a N-methylalanine residue, MeLeu represents a N-methylleucine residue, Melle represents a N-methylisoleucine residue, and amino acid residues other than Gly each represent a D-, L-, or DL-amino acid residue, or a pharmaceutically acceptable salt thereof.
H-Gly-Asn-Trp-His-Gly-Thr-Ala-Pro-Asp-Trp-Val-Tyr-Phe-Ala-His-Le u-Ser-Met-Ile-Trp-OH, SEQ ID NO.:
- 21, H-Gly-Asn-Trp-His-Gly-Thr-Ala-pro-Asp-Trp-Val-Tyr-Phe-Ala-His-Leu-Thr-Thi- Ile-Trp-OH, SEQ ID NO.:
- 17;
- H-Gly-Asn-Trp-His-Gly-Thr-Ala-Pro-Asp-Trp-Val-Tyr-Phe-Ala-His-Leu-Thr-Cha- Ile-Trp-OH, SEQ ID NO.:
- 14 H-Gly-Asn-Trp-His-Gly-Thr-Ala-pro-Asp-Trp-Val-Tyr-Phe-Ala-His-Leu-Thr-Met- Ile-Trp-OH, SEQ ID NO.:
- 18;
- HOOCCH.sub.2 CH.sub.2 CO-Gly-Asn-Trp-His-Gly-Thr-Ala-Pro-AsP-Trp-Val-Tyr-Phe-Ala-His-Leu-Asp-Ile -Ile-Trp-OH, SEQ ID NO.:
- 1;
- H-Gly-Asn--Trp-His-Gly-Thr-Ala-pro-Asp-Trp-Val-Tyr-Phe-Ala-His-Leu-Thr-Leu -Ile-Trp-OH, SEQ ID NO.:
- 13;
- or a pharmaceutically acceptable salt thereof.
##STR26## or a pharmaceutically acceptable salt thereof.
##STR28## or a pharmaceutically acceptable salt thereof.
##STR29## or a pharmaceutically acceptable salt thereof.
Dependencies are inferred from the claim text.