Ligands for integrin αvβ6, synthesis and uses thereof

US10562936B2 · kind B2 · utility

Assignee

• TECHNISCHE UNIVERSITÄT MÜNCHEN · DE

Inventors

• Tobias Kapp · Lörrach, DE
• Horst Kessler · Schwalbach, DE
• Oleg Maltsev · Kufstein, AT

Key dates

• Filing date: Sep 19, 2016
• Grant date: Feb 18, 2020
• Expiry date: Sep 19, 2036

Classification

• Technology area (CPC A): Human Necessities
• CPC primary: A61K49/0056
• WIPO field: Pharmaceuticals
• WIPO sector: Chemistry

Abstract

Disclosed are compound exhibiting highly active and selective binding to αvβ6 integrin, which are represented by the following general formula (I): Cyclo-(Arg-X1-Asp-X2-X3-X4-X5-X6-X7) (I) wherein the variables groups X to X have the following meanings X1: Ser, Gly, Thr, X2: Leu, lie, Nle, Val, Phe, X3: Gly, Ala, X4: Leu, He, Nle, Val, Phe, Lys, Tyr, Trp, Arg, X5: D-Pro, N-Me-D-lipophilic amino acids, X6: Pro, N-Me-amino acids, N-Me-Lys, N-Me-Lys(Ac), and X7; Ala, Leu, He, Nle, Val, Phe, Tyr, Trp or wherein the sub-sequence -X5-X6- 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): (X0)n1L(X8)n2 wherein Xo 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, X8 represents 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 …