雜環基蒽醌衍生物及其合成方法SUBSTITUTED NAPHTO[2,3-F]QUINOXALINE-7,12-DIONES AND PHARMACEUTICAL UTILITY THEREOF

專利類型

發明

專利國別 (專利申請國家)

美國

專利申請案號

13/070,147

專利證號

US 8,470,824 B2

專利獲證名稱

雜環基蒽醌衍生物及其合成方法SUBSTITUTED NAPHTO[2,3-F]QUINOXALINE-7,12-DIONES AND PHARMACEUTICAL UTILITY THEREOF

專利所屬機關 (申請機關)

國防醫學院

獲證日期

2013/06/25

技術說明

一種下式(I)表示具有個別取代基之雜環基蒽醌(heteroannelated anthraquinone)衍生物，尤指包含該衍生物之製備，以及抑制癌細胞生長活性。本研究係合成一系列1,2-heteroannelated anthraquinone 衍生物進行生物活性評估，來探討此系列新穎化合物對端粒酶的抑制活性。藥理活性試驗的方法主要是端粒序列複製法 (TRAP assay)。端粒序列複製法主要是評估化合物對端粒自行形成的特殊結構G-quadruplex的穩定情形。在端粒序列複製法中，具有抑制端粒酶的為M9、M9a、A4及A5。本研究希望從此系列化合物中，尋找具有端粒酶抑制作用的化合物能繼續發展成為具有潛力的抗癌藥物，並且希望以後能在蒽醌類化合物中找出對抑制端粒酶最有活性的取代位置及取代基。 A novel heteroannelated anthraquinone derivative having respective substituent groups is provided. The novel anthraquinone derivative having the potential for becoming an anticancer agent is presented by the following formula (I). A series of 1,2-heteroannelated anthraquinones and anthra[1,2-d]imidazole-6,11-dione tetracyclic analogues with different side chain were prepared using an various synthetic route via acylation, cyclization, condensation, and intramolecular hetercyclization. Tetracyclic system containing alkyl and aryl, aromatic and heterocyclic, linear and cyclic, polar and apolar, and basic and acids residues were incorporated. They were evaluated for their effects on telomerase activity, hTERT expression, cell proliferations, and in vitro cytotoxicity against NCI 60 cell line human tumor screen. Further studies did not reveal any compound that showed potent and significant on telomerase inhibitory activity and hTERT respressing ability.

備註

本部(收文號1090029737)同意該校109年5月22日國院研發字第1090001915號函申請終止維護專利(國防醫學院)

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