2-苯胺基-6-甲基苯并噻唑衍生物及其製備方法與用途2-ANILINO-6-METHYLBENZOTHIAZOLE DERIVATIVES AND THE PREPARATION PROCESSES AND USES THEREOF

專利類型

發明

專利國別 (專利申請國家)

中華民國

專利申請案號

103106847

專利證號

I 543973

專利獲證名稱

2-苯胺基-6-甲基苯并噻唑衍生物及其製備方法與用途2-ANILINO-6-METHYLBENZOTHIAZOLE DERIVATIVES AND THE PREPARATION PROCESSES AND USES THEREOF

專利所屬機關 (申請機關)

高雄醫學大學

獲證日期

2016/08/01

技術說明

本研究合成各系列之苯胺苯并噻唑類衍生物並對其抗C型肝炎病毒進行活性評估和生物活性之探討。結果發現所合成的衍生物對C型肝炎病毒皆呈現出抑制活性的反應，我們並藉此進一步釐清其結構與活性上的關係。在苯胺苯并噻唑類衍生物中，發現化合物2-(4’-nitroanilino)-6-methylbenzothiazole (EC50 = 8 microM) 表現出非競爭性抑制NS5B聚合酶而具有抑制C型肝炎病毒複製的活性，並由電腦分子模擬計算出與C型肝炎病毒NS5B聚合酶的最佳結合構型位於Thumb II Pocket。此外，化合物2-(4’-nitroanilino)-6-methylbenzothiazole與干擾素、telaprevir、BMS790052和PSI7977合併使用後對抑制C型肝炎病毒的複製呈現協同作用。由這些結果推測，此類衍生物具備發展成為抗C型肝炎病毒小分子抑制劑的潛力。 In this study, the anti-HCV activities of the synthesized series of anilinobenzothiazoles were evaluated and their biological activities were discussed. Based on this outcome, the relationships of their structures and activities were further illustrated. Among anilinobenzothiazoles, compound 2-(4’-nitroanilino)-6-methylbenzothiazole (EC50 = 8 microM) was observed to against NS5B polymerase by a non-competitive mode of inhibition. The best binding pose which calculated by computer molecular modeling of compound 2-(4’-nitroanilino)-6-methylbenzothiazole was located in the Thumb II Pocket of HCV RdRp. Moreover, compounds 2-(4’-nitroanilino)-6-methylbenzothiazole displayed the synergistic decreased in HCV RNA levels with the combination of IFN, telpariver, BMS790052 or PSI7977. As a consequence, it is suggested that this series of synthesized derivatives are able to be developed as anti-HCV small molecule inhibitors.

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智財保護與科技管理組

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07-3138030

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