公开(公告)号：EP2784061A1

公开(公告)日：2014-10-01

申请号：EP12851308.2

申请日：2012-11-26

申请人： Universidade Federal De Santa Catarina

发明人： NUNES, Ricardo José ,  MASCARELLO, Alessandra ,  YUNES, Rosendo Augusto ,  STUMPF, Taisa Regina ,  LEAL, Paulo Cesar ,  YUNES, José Andres ,  PEREIRA DE SOUZA MELO, Carolina ,  CANEVAROLO, Rafael Renatino ,  DOMENEGHINI CHIARADIA, Louise ,  BORTOLINI SILVEIRA, André ,  LARANJEIRA, Anqelo Brunelli Albertoni

IPC分类号： C07C251/86 ,  C07D271/107 ,  C07D233/54 ,  C07D333/02 ,  A61K31/166 ,  A61K31/4164 ,  A61K31/381 ,  A61P35/02

CPC分类号： C07D333/22 ,  C07C243/38 ,  C07C251/86 ,  C07D233/64 ,  C07D271/107 ,  C07D333/36

摘要： The present invention relates to acyl-hydrazone compounds, in particular 3,4,5-trimethoxyphenyl-hydrazide derivatives, as well as the oxadiazole analogs thereof and other similar compounds, and to the pharmaceutical use of the same for the treatment of various diseases associated with cell proliferation, such as leukemias, including acute lymphoblastic leukemia (ALL), tumours and inflammation. Acyl-hydrazones have been obtained having activity similar to that of the compound used as a standard in experiments (colchicine). The greater selectivity of the compounds according to the invention is an important feature, associated with fewer side effects than the pharmaceuticals used at present in clinical treatments. The synthetised acyl-hydrazones, more particularly the compounds 02 and 07, exhibited important anti-leukemic activity, which suggests 02 and 07 as candidates to pharmaceutical prototypes, or to pharmaceuticals for the treatment of leukemias, in particular acute lymphoblastic leukemia (ALL), tumours and other proliferative diseases, such as inflammation. The action mechanism of the most active compounds was determined by using DNA microarrays and subsequent tests indicated by the chip, besides selectivity studies in healthy human lymphocytes.

摘要翻译： 本发明涉及酰基腙化合物，特别是3,4,5-三甲氧基苯基 - 酰肼衍生物，以及它们的恶二唑类似物和其它类似化合物，以及用于各种疾病相关的治疗药物使用相同的 与细胞增殖，：如白血病，包括急性淋巴细胞白血病（ALL），肿瘤和炎症。 酰基水螅区havebeen得到具有类似于化合物活性做了用作实验标准（秋水仙碱）。 化合物gemäß发明的更大的选择性是重要的特征，具有副作用比在临床治疗目前使用的药物较少相关联。 所述synthetised酰基水螅区，更特别地是化合物02和07表现出重要的抗白血病活性，这表明02和07作为候选药物的模板，或者以药物用于治疗白血病，特别是急性淋巴细胞白血病（ALL） 肿瘤和其它增殖性疾病，：如炎症。 该确定性通过使用DNA微阵列和由芯片所指出的，除了在健康人淋巴细胞的选择性的研究随后的试验开采的最活跃的化合物的作用机制。