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LIGANDS POUR L'INTÉGRINE ALPHAVBETA8, SYNTHÈSE ET UTILISATIONS DE CEUX-CI
专利权人:
Technische Universität München
发明人:
申请号:
EP18710882.4
公开号:
EP3596105A1
申请日:
2018.03.16
申请国别(地区):
EP
年份:
2020
代理人:
摘要:
Disclosed are compounds represented by the following general formula (I): Cyclo-(Arg-Gly-Asp-X1-X2-X2-X4-X5) (I) wherein the variables groups X1 to X5 have the following meanings X1: Leu, Ile, Nle, Val, Tyr, Phe; X2: D-amino acid such as D-Pro, N-Me-D-Phe; X3: Pro, N-Me-amino acid such as N-Me-Lys, N-Me-Lys(Ac); Pro-Rx3, N-Me-Lys-Rx4; X4: Gly, Ala, Ser, Thr; X5: 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 —NH2, —OH, —NH—Ac, —NH-hexyne, and wherein Lys-Rx4 represents a lysine residue, wherein the ω-amino nitrogen atom carries a group of the formula -L4-R4, wherein L4 is selected from the group consisting of covalent bond, —C(O)—, and —C(O)—O—, . . . , and wherein R4 is selected from the group consisting of —(CH2)n-C≡CH with n=0, 1, 2, 3, 4, 5, 6, 7 or 8, or wherein the sub-sequence -X2-X3- represents a β-turn mimetic diffeωωring 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 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, X8 represents 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.La présente invention concerne des composés représentés par la formule générale suivante (I) : Cyclo-(Arg-Gly-Asp-X1-X2-X3-X4-X5) (I) dans laquelle, les groupes de variables X1 à X5 ont les significations suivantes X1 : Leu, Ile, Nle, Val, Tyr, Phe ; X2
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