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Synthesis and antitumor activities of 2-(piperidin-4-yl)-thiazole-4-carboxamides analogues of tubulysins

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Tubulysins are a family of natural products that exhibit potent antitumor activities, which have attracted much attention from synthetic and medicinal chemists. Previous attempts to aromatize the Tuv part of tubulysin analogues led to a loss in antitumor activity, which suggested that the Ile and Tuv fragments of these analogues were adopting different conformations than the natural products. In this study, a series of 2-(piperidin-4-yl)-thiazole-4- carboxamides have been prepared to investigate whether an intramolecular H-bond between key NH and OH groups is responsible for the conformational control. |

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