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US 5,410,019 AGranted
Therapeutic peptides
AssigneeThe Administrators of the Tulane Educational Fund
InventorsDavid H. Coy, Jacques-Pierre Moreau
Life of this patent
Estimating the term…
Abstract
A linear peptide which is an analog of naturally occurring, biologically active substance P having an active site and a binding site responsible for the binding of the peptide to a receptor on a target cell. The analog has a non-peptide bond instead of a peptide bond between an amino acid residue of the active site and an adjacent amino acid residue, or a synthetic, a .beta.-amino acid, or a .alpha.-amino acid residue replacing two amino acid residues of the active site.
Claims9
A substance P analog of the formula:
- ##STR10## wherein A.sup.1 =the D or L isomer of Arg, Lys, or Lys-.epsilon.-NH-R.sub.20 in which R.sub.20 is any of H, C.sub.1-12 alkyl, C.sub.7-10 phenylalkyl, or COE.sub.10 with E.sub.10 being C.sub.1-20 alkyl, C.sub.3-20 alkenyl, C.sub.3-20 alkynyl, phenyl, naphthyl, or C.sub.7-10 phenylalkyl;
- or is deleted;
- A.sup.2 =the D or L isomer Pro;
- or is deleted;
- A.sup.3 =the D or L isomer of Lys, or Lys-.epsilon.-NH-R.sub.22 in which R.sub.22 is any of H, C.sub.1-12 alkyl, C.sub.7-10 phenylalkyl, or COE.sub.12 with E.sub.12 being C.sub.1-20 alkyl, C.sub.3-20 alkenyl, C.sub.3-20 alkynyl, phenyl, naphthyl, or C.sub.7-10 phenylalkyl;
- or is deleted;
- A.sup.4 =the D or L isomer of Pro;
- or is deleted;
- A.sup.5 =the D or L isomer of Asp, Gln, .beta.-Nal, Trp, Phe, o-X-Phe in which X is F, C1, Br, NO.sub.2, OH, or CH.sub.3, or p-X-Phe in which X is F, Cl, Br, NO.sub.2, OH, or CH.sub.3 ;
- or is deleted;
- A.sup.6 =the D or L isomer of Ala, Arg, Ser, Pro, Gln, p-Glu, Asn, .beta.-Nal, Trp, Phe, o-X-Phe in which X is F, Cl, Br, NO.sub.2, OH, or CH.sub.3, or p-X-Phe in which X is F, Cl, Br, NO.sub.2, OH, or CH.sub.3 ;
- A.sup.7 =the D or L isomer of Val, Thr, Phe, Trp, .beta.-Nal, o-X-Phe in which X is F, Cl, Br, NO.sub.2, OH, or CH.sub.3, or p-X-Phe in which X is F, Cl, Br, NO.sub.2, OH, or CH.sub.3 ;
- A.sup.8 =the identifying group of Gly or the D or L isomer of Val, Trp, .beta.-Nal, Phe, o-X-Phe in which X is F, Cl, Br, NO.sub.2, OH, or CH.sub.3, or p-X-Phe in which X is F, Cl, Br, NO.sub.2, OH, or CH.sub.3 ;
- A.sup.9 =Gly or the D or L isomer of Sar, His, Trp, .beta.-Nal, Phe, o-X-Phe in which X is F, Cl, Br, NO.sub.2, OH, or CH.sub.3, or p-X-Phe in which X is F, Cl, Br, NO.sub.2, OH, or CH.sub.3 ;
- A10=Gly or the identifying group of the D or L isomer of Trp, .beta.-Nal, Leu, Nle, Ala, cyclohexyl-Ala, Val, Ile, Met, Phe, o-X-Phe in which X is, Cl, Br, NO.sub.2, OH, or CH.sub.3, or p-X-Phe in which X is F, Cl, Br, NO.sub.2, OH, or CH.sub.3 ;
- A11=Gly or the identifying group of the D or L isomer of Trp, .beta.-Nal, Leu, Nle, Ala, Val, Ile, Met, Phe, o-X-Phe in which X is F, Cl, Br, NO.sub.2, OH, or CH.sub.3, or p-X-Phe in which X is F, Cl, Br, NO.sub.2, OH, or CH.sub.3 ;
- or is deleted;
- R.sub.5 is CH.sub.2 --NH and V.sup.1 is ##STR11## in which each R.sub.10, R.sub.11, and R.sub.12 independently, is H, C.sub.1-12 alkyl, C.sub.7-10 phenylalkyl, or C.sub.12-20 naphthylalkyl;
- further provided that, where A.sup.5 is Asp, A.sup.6 is Ser, A.sup.7 is Phe, A.sup.8 is Val, A.sup.9 is Gly, A.sup.10 is Leu, and A.sup.11 is Leu, at least one of A.sup.1, A.sup.2, A.sup.3, or A.sup.4 must be present;
- or a pharmaceutically acceptable salt thereof.
17 more elements
A substance P analog of the formula:
- ##STR12## wherein A.sup.21 =the D or L isomer of Arg, Lys, or Lys-.epsilon.-NH-R80 in which R.sub.80 is any of H, C.sub.1-12 alkyl, C.sub.7-10 phenylalkyl, or COE.sub.20 with E.sub.20 being C.sub.1-20 alkyl, C.sub.3-20 alkenyl, C.sub.3-20 alkynyl, phenyl, naphthyl, or C.sub.7-10 phenylalkyl;
- or is deleted;
- A.sup.22 =the D or L isomer of Pro;
- or is deleted;
- A.sup.23 =the D or L isomer of Lys or Lys-.epsilon.-NH-R.sub.82 in which R.sub.82 is any of H, C.sub.1-12 alkyl, C.sub.7-10 phenylalkyl, or COE.sub.22 with E.sub.22 being C.sub.1-20 alkyl, C.sub.3-20 alkenyl, C.sub.3-20 alkynyl, phenyl, naphthyl, or C.sub.7-10 phenylalkyl;
- or is deleted;
- A.sup.24 =the D or L isomer of Pro;
- or is deleted;
- A.sup.25 =the identifying group of the D or L isomer of Asp, Gln, B-Nal, Trp, Phe, o-X-Phe in which X is F, Cl, Br, NO.sub.2, OH, or CH.sub.3, or p-X-Phe in which X is F, Cl, Br, NO.sub.2, OH, or CH.sub.3 ;
- or is deleted together with NH--CH bonded thereto;
- A.sup.26 =the identifying group of the D or L isomer of Arg, Sar, Pro, Gln, pGlu, Phe, Trp, cyclohexyl-Ala, or Asn;
- A27=the identifying group of D-Trp;
- or the identifying group of the D or L isomer of Leu, Phe, or cyclohexyl-Ala;
- A.sup.28 =the identifying group of the D or L isomer of any one of the amino acids Val, .beta.-Nal, Phe, o-X-Phe in which X is F, Cl, Br, NO.sub.2, OH, or CH.sub.3, or p-X-Phe in which X is F, Cl, Br, NO.sub.2, OH, or CH.sub.3 ;
- A.sup.29 =the identifying group of the amino acid D-Trp;
- or the identifying group of the D or L isomer of any of Leu, Phe, or cyclohexyl-Ala;
- A.sup.30 =the identifying group of the D or L isomer of any one of the amino acids Leu, Nle, Ala, cyclohexyl-Ala, Val, Ile, Met, Gly, Phe, Trp, .beta.-Nal, o-X-Phe in which X is F, Cl, Br, NO.sub.2, OH, or CH.sub.3, or p-X-Phe in which X is F, Cl, Br, NO.sub.2, OH, or CH.sub.3 ;
- A.sup.31 =the identifying group of the D or L isomer of any one of the amino acids Trp, .beta.-Nal, Leu, Nle, Ala, Val, Ile, Met, Gly, Phe, o-X-Phe in which X is F, Cl, Br, NO.sub.2, OH, or CH.sub.3, or p-X-Phe in which X is F, Cl, Br, NO.sub.2, OH, or CH.sub.3 ;
- R.sub.54 is CO--NH or CO--NCH.sub.3 if A.sup.25 with NH--CH is not deleted, is NH if A.sup.25 with NH--CH is deleted;
- each R.sub.56, R.sub.62, and R.sub.64, independently, is any of CO--NH or CH.sub.2 --NH;
- R.sub.58 is CO--NR.sub.69 in which R.sub.69 is H or C.sub.1-12 alkyl, or CH.sub.2 --NH;
- R.sub.60 is CO--NH;
- and V.sup.10 is ##STR13## in which each R.sub.66, R.sub.67, and R.sub.68 independently, is H, C.sub.1-12 alkyl, C.sub.7-10 phenylalkyl, or C.sub.12-20 naphthylalkyl;
- provided that, at least one of R.sub.56, R.sub.58, R.sub.62, or R.sub.64 is CH.sub.2 NH;
- or a pharmaceutically acceptable salt thereof.
22 more elements
Dependencies are inferred from the claim text.