Compounds comprising a fibroblast activation protein ligand and use thereof

A compound comprising a cyclic peptide of formula (I)

• and an N-terminal modification group A attached to Xaa1,
• wherein
• the peptide sequence is drawn from left to right in N to C-terminal direction,
• Xaa1 is a residue of an amino acid of formula (II)
• wherein
• R1a is —NH—
• R1b and R1c are each and independently from each other H or CH3,
• n=0 or 1,
• the N-terminal modification group A is covalently attached to the nitrogen atom of Xaa1,
• the carbonyl group of Xaa1 is covalently attached to the nitrogen of Xaa2;
• Xaa2 is a residue of an amino acid of formula (III), (IV) or (XX)
• wherein
• R2a, R2b and R2c are each and independently selected from the group consisting of (C1-C2)alkyl and H, wherein said (C1-C2)alkyl is optionally substituted by a substituent selected from the group consisting of OH, NH2, halogen and (C5-C7)cycloalkyl,
• p=0, 1 or 2
• v=1 or 2
• w=1, 2 or 3 and
• the amino acid of formula (IV) is optionally substituted by one or two substituents each and individually selected from the group consisting of methyl, OH, NH2 and F at indicated ring positions 3 and/or 4;
• Xaa3 is a residue of an amino acid of formula (V) or (XX)
• wherein
• X3 is selected from the group consisting of CH2, CF2, CH—R3b, S, O and NH, p=1 or 2
• v=1 or 2
• w=1, 2 or 3,
• R3a is selected from the group consisting of H, methyl, OH, NH2 and F,
• R3b is selected from the group consisting of methyl, OH, NH2 and F;
• Xaa4 is a residue of an amino acid of formula (VI)
• wherein
• R4a is selected from the group consisting of H, OH, COOH, CONH2, X4 and —NH—CO—X4, wherein X4 is selected from the group consisting of (C1-C6)alkyl, (C5-C6)aryl and (C5-C6)heteroaryl, and X4 is optionally substituted by one or two substituents each and individually selected from the group consisting of methyl, CONH2, halogen, NH2 and OH;
• q=1, 2 or 3, wherein optionally one or two hydrogens of said one, two or three CH2-groups are each and individually substituted by methyl, ethyl, (C5-C6)aryl or (C5-C6)heteroaryl,
• R4b is methyl or H;
• Xaa5 is a residue of an amino acid of structure (VII)
• wherein
• R5 is selected from the group consisting of OH and NH2, and
• r=1, 2 or 3;
• Xaa6 is a residue of an amino acid selected from the group consisting of an aromatic L-α-amino acid and a heteroaromatic L-□-amino acid;
• Xaa7 is a residue of an amino thiol or an amino acid of formula (IX),
• R7a is selected from the group consisting of —CO—, —COOH, —CONH2, —CH2—OH, —(CO)—NH—R7b, —(CO)—(NR7c)—R7b and H, wherein R7b and R7c are each and independently (C1-C4)alkyl and
• t=1 or 2;
• Yc is a cyclization element of formula (X) which is either present or absent;
• wherein if Yc is absent, the S atom of Xaa1 and the S atom of Xaa7 are covalently linked to each other forming a cyclic structure of formula (XXII)
• wherein
• n=0 or 1,
• t=1 or 2,
• and
• wherein if Yc is present, the S atom of Xaa1 is linked to Yc by a thioether linkage and the S atom of Xaa7 is linked to Yc by a thioether linkage forming a cyclic structure of formula (XXI)
• wherein
• n=0 or 1,
• t=1 or 2,
• wherein the N-terminal modification group A is either a blocking group Abl or an amino acid Aaa.