Synthesis of Indazole Derivatives as Nrf2 Regulators

• Main Authors: Jau-Yang Chen, 陳朝陽
• Other Authors: Chih-Shiang Chang
• Format: Others
• Language: zh-TW
• Published: 2013
• Online Access: http://ndltd.ncl.edu.tw/handle/6rhbrm

碩士 === 中國醫藥大學 === 藥物化學研究所碩士班 === 101 === Nuclear factor (erythoid-derived 2)-like 2 (Nrf2) is a critical transcription factor regulating a cellular protective response that defends cells against toxic insults from a broad spectrum of chemicals. The activation of Nrf2 possesses chemopreventive activity against chemical carcinogenesis. A series of indazole derivatives was synthesized and bioevaluated for the Nrf2 activity on the nasopharyngeal carcinoma TW01-9ARE、TW01-15ARE、HSC3-9ARE. The results were shown that the introduction of Cl moiety into 4-position of indazole ring possessed the activation of Nrf2 enhancer. However, the substitution of primary amine or secondary amine moiety on 4-position of indazole ring attenuated the Nrf2 activity. Heterocyclic substituted pyridine as the most obvious inhibitory effect can be applied to chemical adjuvant therapy.