Cancer imaging and treatment

• US 8,614,290 B2
• Filed: 09/01/2008
• Issued: 12/24/2013
• Est. Priority Date: 08/30/2007
• Status: Expired due to Fees

• Current Assignee: Technische Universitat Munchen
• Original Assignee: Technische Universitat Munchen
• Inventors: Kessler, Horst, Dijkgraaf, Ingrid, Wester, Hans Jrgen, Demmer, Oliver
• Primary Examiner(s): Wax, Robert A
• Assistant Examiner(s): AL-AWADI, DANAH J
• Application Number:
  US12/675,151
• Publication Number:
  US 20100240072A1
• Time in Patent Office: 1,940 Days
• Field of Search: None
• US Class Current: 530/321
• CPC Class Codes: A61K 47/55 the modifying agent being also a pharmacologically or therapeutically active agent, i.e. the entire conjugate being a codrug, i.e. a dimer, oligomer or polymer of pharmacologically or therapeutically active compounds
• CPC Class Codes: A61K 51/08 Peptides, e.g. proteins , carriers being peptides, polyamino acids, proteins
• CPC Class Codes: A61K 51/088 conjugates with carriers being peptides, polyamino acids or proteins antibodies A61K51/10
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 35/04 specific for metastasis

Abstract

A compound, or a pharmaceutically acceptable salt or ester thereof, comprises the structure: [(P1-S1_j)_p-L-(S2_q-P2)_r]_t wherein: P1 and P2, which may be the same or different, are cyclic oligopeptide moieties, at least one of P1 and P2 having the motif B-Arg or B-(Me) Arg within the cyclic moiety, wherein B is a basic amino acid, a derivative thereof, or phenylalanine or a derivative thereof; S1 and S2 are spacer groups, which may be the same or different; L is a linker moiety containing at least two functional groups for attachment of the cyclic oligopeptides or spacer groups; n and q are independently 0 or 1; p and r are independently integers of 1 or more; and t is an integer of 1 or more, provided that, when t, p or r is greater than 1, the cyclic oligopeptide moiety, spacer group and/or the value of j or q may be the same or different between the multiple (P1-S1_j) moieties or multiple (S2_q-P2) moieties.

Claims

1. A compound, or a pharmaceutically acceptable salt or ester thereof, comprising the structure:

[(P1-S1_j)_p-L-(S2_q-P2)_r]_t

wherein;

P1 and P2, which may be the same or different, are cyclic oligopeptide moieties, at least one of P1 and P2 having the motif B-Arg or B-(Me)Arg within the cyclic moiety, wherein B is an Nα

-methyl derivative of a basic amino acid, or an N^α

-methyl derivative of phenylalanine;

S1 and S2 are spacer groups, which may be the same or different;

L is a linker moiety containing at least two functional groups for attachment of the cyclic oliqopeptides or spacer groups;

j and q are independently 0 or 1;

p and r are independently integers of 1 or more; and

t is an integer of 1 or more,

provided that, when t, p or r is greater than 1, the cyclic oliqopeptide moiety, spacer group and/or the value of j or q may be the same or different between the multiple (P1-S1_j) moieties or multiple (S2_q-P2) moieties.

2. A compound, or a pharmaceutically acceptable salt or ester thereof, comprising the structure:

[(P1-S1_j)_p-L-(S2_q-P2)_r]_t

wherein;

S1 and S2 are spacer groups, which may be the same or different;

L is a linker moiety containing at least two functional groups for attachment of the cyclic oliqopeptides or spacer groups;

j and q are independently 0 or 1;

p and r are independently integers of 1 or more; and

t is an integer of 1 or more,

P1 and P2, which may be the same or different, are cyclic oliqopeptide moieties, at least one of P1 and P2 is selected from cyclic oligopeptides having the sequence;

cyclo[D-Tyr/(Me)D-Tyr-B-Arg/(Me)Arg-Z-(Ala)_n-X]

wherein B is Orn or D-Orn, the ornithine residue being substituted at N^α

with one or two groups selected from fluorobenzoyl (FB), fluoropropionyl (FP), acetyl (Ac), amido (Am), Me, 1-naphthylmethyl (N1), 2-naphthylmethyl (N2), benzyl (Bz) and acyl spacer moieties, wherein the acyl spacer moiety is an acyl group containing a chain of 1-14 carbons, optionally interrupted by heteroatoms, and having a nucleophilic functional group at its end distal to the ornithine N^α

;

Z is an amino acid containing an aromatic group in its side chain;

n is 1 or 0, provided that n is 1 only when the preceding four amino acids in the cyclic moiety sequence are D-Tyr/(Me)-D-Tyr-Arq-Arq-Nal, Nal being L-3-(2-naphthyl)alanine; and

X is selected from Gly, (Me)Gly, Ala, Dap (diaminopropionic acid), Dap(FP) ((N-fluoropropionyl)-diaminopropionic acid), Dab (diaminobutyric acid), Dab(FP) ((N-fluoropropionyl)-diaminobutyric acid), Dab(FB) ((N-fluorobenzoyl)-diaminobutyric acid) and Dap(FB) ((N-fluorobenzoyl)-diaminopropionic acid);

provided that, when t, p or r is greater than 1, the cyclic oligopeptide moiety, spacer group and/or the value of j or q may be the same or different between the multiple (P1-S1_j) moieties or multiple (S2_g-P2) moieties.