Technical University of Munich

Tobias Kapp

Horst Kessler

Oleg Maltsev

Hans-Jürgen Wester

Margret Schottelius

Theresa Osl

Florian Reichart

The present disclosure relates to imaging and endoradiotherapy of diseases involving chemokine receptor 4 (CXCR4). Provided are compounds which bind or inhibit hCXCR4 and mCXCR4 and furthermore carry at least one moiety which is amenable to labeling. Provided are also medical uses of such compounds.

CXCR4-targeted diagnostic and therapeutic agents with reduced species selectivity

Disclosed are compounds represented by the following general formula (I): Cyclo-(Arg-Gly-Asp-X-X-X-X-X) (I) wherein the variables groups Xto Xhave the following meanings X: Leu, Ile, Nle, Val, Tyr, Phe; X: D-amino acid such as D-Pro, N-Me-D-Phe; X: Pro, N-Me-amino acid such as N-Me-Lys, N-Me-Lys(Ac); Pro-Rx3, N-Me-Lys-Rx4; X: Gly, Ala, Ser, Thr; X: Leu, Ala, Tyr, His, Ile, Nle, Val, Phe wherein Pro-Rx3 represents a proline residue that carries at the C-3, C-4 or C-5 carbon atom and preferably the C-4 carbon atom a functional group selected from &#x2014;NH2, &#x2014;OH, &#x2014;NH&#x2014;Ac, &#x2014;NH-hexyne, and wherein Lys-Rrepresents a lysine residue, wherein the &#x3c9;-amino nitrogen atom carries a group of the formula -L4-R4, wherein L4 is selected from the group consisting of covalent bond, &#x2014;C(O)&#x2014;, and &#x2014;C(O)&#x2014;O&#x2014;, . . . , and wherein R4 is selected from the group consisting of &#x2014;(CH2)n-C&#x2261;CH with n=0, 1, 2, 3, 4, 5, 6, 7 or 8, or wherein the sub-sequence -X-X- represents a &#x3b2;-turn mimetic diffe&#x3c9;&#x3c9;ring 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 X0 represents 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, preferably such that each of n1 and n2 represents 1, wherein n1+n2 represents the number of valencies of the linker and is preferably in the range of from 2 to 6, more preferably 2-5, with the proviso that each of n1 and n2 is at least 1, as well as uses therefore in therapy and imaging.

Ligands for integrin &#x3b1;V&#x3b2;8, synthesis and uses thereof

Disclosed are compound exhibiting highly active and selective binding to &#x3b1;v&#x3b2;6 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 &#x3b2;-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.

Growing community of inventors

Lörrach, Germany

Tobias Kapp