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具有抗黑色素瘤细胞增殖活性的新型咪唑并[1,2-a]吡啶和咪唑并[1,2-a]吡嗪衍生物的设计与合成。

Design and synthesis of new imidazo[1,2-a]pyridine and imidazo[1,2-a]pyrazine derivatives with antiproliferative activity against melanoma cells.

作者信息

Garamvölgyi Rita, Dobos Judit, Sipos Anna, Boros Sándor, Illyés Eszter, Baska Ferenc, Kékesi László, Szabadkai István, Szántai-Kis Csaba, Kéri György, Őrfi László

机构信息

Department of Pharmaceutical Chemistry, Semmelweis University, Budapest, Hungary; Vichem Chemie Research Ltd., Budapest, Hungary.

Vichem Chemie Research Ltd., Budapest, Hungary.

出版信息

Eur J Med Chem. 2016 Jan 27;108:623-643. doi: 10.1016/j.ejmech.2015.12.001. Epub 2015 Dec 12.

Abstract

Melanoma is an aggressive form of skin cancer and it is generally associated with poor prognosis in patients with late-stage disease. Due to the increasing occurrence of melanoma, there is a need for the development of novel therapies. A new series of diarylamide and diarylurea derivatives containing imidazo[1,2-a]pyridine or imidazo[1,2-a]pyrazine scaffold was designed and synthesized to investigate their in vitro efficacy against the A375P human melanoma cell line. We found several compounds expressing submicromolar IC50 values against the A375P cells, from which 15d, 17e, 18c, 18h, 18i demonstrated the highest potencies with IC50 below 0.06 μM.

摘要

黑色素瘤是一种侵袭性皮肤癌,晚期患者通常预后较差。由于黑色素瘤发病率不断上升,需要开发新的治疗方法。设计并合成了一系列含有咪唑并[1,2-a]吡啶或咪唑并[1,2-a]吡嗪骨架的二芳基酰胺和二芳基脲衍生物,以研究它们对A375P人黑色素瘤细胞系的体外疗效。我们发现几种化合物对A375P细胞的IC50值低于亚微摩尔,其中15d、17e、18c、18h、18i表现出最高活性,IC50低于0.06 μM。

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