2-芳香基-4-喹啉酮的新穎親水性衍生物及其作為抗癌劑的用途Derivatives of 2-aryl-4-quinolones having an aminoalkyl group as anticancer agents

專利類型

發明

專利國別 (專利申請國家)

瑞士

專利申請案號

11010020.3

專利證號

2455369

專利獲證名稱

2-芳香基-4-喹啉酮的新穎親水性衍生物及其作為抗癌劑的用途Derivatives of 2-aryl-4-quinolones having an aminoalkyl group as anticancer agents

專利所屬機關 (申請機關)

中國醫藥大學

獲證日期

2014/09/03

技術說明

合成一系列親水性2-芳基喹啉- 4-酮(HAQ)衍生物並評估其抗癌活性。迄今為止，在評價的化合物中，以2-(2-氟苯基)-6,7-亞甲二氧基喹啉-4-酮-磷酸單鈉鹽(CHM-2133-P-Na)和2 -(3-氟苯基)-5-羥基-6-甲基喹啉-4-酮-磷酸單鈉鹽(CHM-2134-P-Na)為最具有潛力之化合物。CHM-2133-P-Na對卵巢癌SKOV 3裸鼠移植瘤模型具有良好的抗腫瘤活性。CHM-2133-P-Na在安全性藥理研究結果，並不會明顯影響大多數所測試的酵素之正常生理功能。另一方面，CHM-2134-P-Na活性超過doxorubicin，在Hep3B肝癌裸鼠移植瘤模型媲美CHM-2133-P-Na。總之，CHM-2133-P-Na和CHM-2134-P-Na是具有潛力的臨床候選藥物，目前正在進行臨床研究。 A series of hydrophilic 2-arylquinolin-4-one (HAQ) derivatives were synthesized and evaluated for their anticancer activity. To date, among evaluated compounds, 2-(2-fluorophenyl)-6,7-methylenedioxyquinolin-4-one monosodium phosphate (CHM-2133-P-Na) and 2-(3-fluorophenyl)-5-hydroxy-6-methylquinolin-4-one monosodium phosphate (CHM-2134-P-Na) were the most the promising compounds. CHM-2133-P-Na possessed excellent antitumor activity in a SKOV 3 xenograft nude mice model. Safety pharmacology profiling of CHM-2133-P-Na showed no significant effect on normal biological functions of most enzymes tested. On the other hand, CHM-2134-P-Na exceeded the activity of doxorubicin and was comparable to CHM-2133-P-Na in a Hep3B xenograft nude mice model. In summary, CHM-2133-P-Na and CHM-2134-P-Na are promising clinical candidates, and are currently under clinical study.

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