Ligands for integrin αvβ6, synthesis and uses thereof

Abstract

Disclosed are compound exhibiting highly active and selective binding to αvβ6 integrin, which are represented by the following general formula (I): Cyclo-(Arg-X-Asp-X-X-X-X-X-X) (I) wherein the variables groups X to X have the following meanings X: Ser, Gly, Thr, X: Leu, lie, Nle, Val, Phe, X: Gly, Ala, X: Leu, He, Nle, Val, Phe, Lys, Tyr, Trp, Arg, X: D-Pro, N-Me-D-lipophilic amino acids, X: Pro, N-Me-amino acids, N-Me-Lys, N-Me-Lys(Ac), and X; Ala, Leu, He, Nle, Val, Phe, Tyr, Trp or wherein the sub-sequence -X-X- represents a β-turn mimetic differing from the meanings above, or pharmaceutically acceptable salts, esters, solvates, polymorphs or modified forms thereof represented by the following general formula (II): (X)L(X)wherein Xrepresents the compound of the general formula (I) as specified above (excluding one hydrogen atom to allow bonding to the linker), L represents a linker, Xrepresents the effector moiety and wherein n1 and n2 are each independently selected from the range of 1 to 5, wherein n1+n2 represents the number of valencies of the linker and is preferably in the range of from 2 to 6, more preferably 3-5, with the proviso that each of n1 and n2 is at least 1, as well as uses therefore in therapy and imaging.