具有CXCR7 调节活性的模板固定的肽模拟物

摘要

新的通式(I)的模板固定的β‑发夹肽模拟物其中单独的元件T或P是自羰基(C=O)连接点以顺时针方向连接至下一元件的氮(N)的α‑氨基酸残基，并且其中所述元件取决于它们在链中的位置定义于说明书和权利要求书中，具有作用于受体CXCR7的特性。从而，这些β‑发夹肽模拟物能够用于治疗或预防皮肤病学障碍，代谢病，炎性疾病，纤维化疾病，传染病，神经学疾病，心血管疾病，呼吸系统疾病，胃肠道障碍，泌尿学疾病，眼疾病，口腔学疾病，血液学疾病和癌症；或用于干细胞活化。

主权项

通式(I)的化合物其中单独的元件T或P自羰基(C＝O)连接点以任一方向连接至下一元件的氮(N)，所述化合物选自环(‑Trp‑^DPhe‑Trp‑Arg‑^DPro((4S)NH₂)‑Tic‑)；环(‑Trp‑^DPhe‑Trp‑Arg‑^DPro((4R)NH₂)‑Tic‑)；环(‑Ala‑^DPhe‑Trp‑Arg‑^DPro((4R)NH₂)‑Tic‑)；环(‑Tyr‑^DPhe‑Trp‑Arg‑^DPro((4R)NH₂)‑Tic‑)；环(‑Trp‑^DPhe‑Trp‑Orn‑^DPro((4R)NH₂)‑Tic‑)；环(‑Trp‑^DPhe‑Trp‑Dab‑^DPro((4R)NH₂)‑Tic‑)；环(‑Trp‑^DPhe‑Trp‑Lys‑^DPro((4R)NH₂)‑Tic‑)；环(‑Trp‑^DPhe‑Trp‑His‑^DPro((4R)NH₂)‑Tic‑)；环(‑Arg‑^DPhe‑Trp‑Arg‑^DPro((4R)NH₂)‑Tic‑)；环(‑Pip‑^DPhe‑Trp‑Arg‑^DPro((4R)NH₂)‑Tic‑)；环(‑hArg‑^DPhe‑Trp‑Arg‑^DPro((4R)NH₂)‑Tic‑)；环(‑Agb‑^DPhe‑Trp‑Arg‑^DPro((4R)NH₂)‑Tic‑)；环(‑3Pal‑^DPhe‑Trp‑Arg‑^DPro((4R)NH₂)‑Tic‑)；环(‑Arg‑^DPhe‑Trp‑hArg‑^DPro((4R)NH₂)‑Tic‑)；环(‑Arg‑^DPhe‑Trp‑Arg‑^DPro((4S)NH₂)‑Tic‑)；环(‑Trp‑^DPhe‑Trp‑Arg‑^DPro((4R)NH₂)‑Oic‑)；环(‑Arg‑^DPhe‑Trp‑Arg‑^DPro((4R)NH₂)‑Oic‑)；环(‑Trp‑^DPhe‑Trp‑Arg‑^DPro‑Pro((4S)F)‑)；环(‑Trp‑^DPhe‑Trp‑Arg‑^DPro‑Pro((4S)NH₂)‑)；环(‑Trp‑^DPhe‑Trp‑Arg‑^DPro‑Pro((4R)NH₂)‑)；环(‑Trp‑^DPhe‑Trp‑Arg‑^DPro‑Mor‑)；环(‑Arg‑^DPhe‑Trp‑Arg‑^DPro‑(4S)‑Hyp(Bn)‑)；环(‑Trp‑^DPhe‑Trp‑Arg‑^DPro((4S)OH)‑(4S)‑Hyp(Bn)‑)；环(‑Trp‑^DPhe‑Trp‑Arg‑^DPro((4R)NH₂)‑(4S)‑Hyp(Bn)‑)；环(‑Trp‑^DPhe‑Trp‑Orn(A56)‑^DPip‑Pro((3S)OH)‑)；环(‑Ala(1Pyraz)‑^DPhe‑Trp‑Arg‑^DPro((4R)NH₂)‑Tic‑)；环(‑Ala(Tet)‑^DPhe‑Trp‑Arg‑^DPro((4R)NH₂)‑Tic‑)；环(‑Orn(Ar2)‑^DPhe‑Trp‑Arg‑^DPro((4R)NH₂)‑Tic‑)；环(‑Orn(A56)‑^DPhe‑Trp‑Arg‑^DPro((4R)NH₂)‑Tic‑)；环(‑Trp‑^DPhe‑Trp‑Orn(Ar7)‑^DPro((4R)NH₂)‑Tic‑)；环(‑Trp‑^DPhe‑Trp‑Orn(A56)‑^DPro((4R)NH₂)‑Tiq‑)；环(‑Trp‑^DPhe‑Trp‑Orn(A56)‑^DPro((4R)NH₂)‑Tic‑)；及其药学上可接受的盐；其中Agb是指(S)‑2‑氨基‑4‑胍基丁酸；Orn(Ar2)是指(S)‑2‑氨基‑5‑(嘧啶‑2‑基氨基)戊酸；Orn(A56)是指(S)‑2‑氨基‑5‑(1,4,5,6‑四氢嘧啶‑2‑基氨基)戊酸；Orn(Ar7)是指(S)‑2‑氨基‑5‑(((1‑甲基‑1H‑咪唑‑2‑基)甲基)氨基)戊酸。