摘要
目的设计合成8-羟基喹啉酮类β_(2)受体激动剂,并对其生物活性进行评价。方法以8-羟基喹啉为起始原料,经氧化、乙酰化、Fries重排、苄基保护、溴代、Delepine反应得到关键中间体7,7与含不同取代基的酰氯经酰化、还原、脱苄基反应合成2-酰氨基-1-芳基乙醇类和2-磺酰氨基-1-芳基乙醇类目标化合物。采用选择性高表达β_(2)受体的HEK293细胞,通过测试细胞内cAMP的累积量评价化合物对β_(2)受体的激动活性(EC)。结果与结论合成了20个未见文献报道的新化合物,其结构经ESI-MS和1H-NMR谱确证;细胞活性评价结果表明,目标化合物对β受体激动活性均相对较低,其中活性较好的化合物10b与10h,EC值分别为0.96、0.60μmol·L^(-1)。
A series of compounds bearing 8-hydroxyquinolinone scaffold were designed and synthesized, and their β_(2)-adrenergic receptor agonic activities were evaluated.8-Hydroxyquinoline was used as the starting material.After oxidation, acetylation, Fries rearrangement, benzyl protection, bromination, and Delepine reaction, the key intermediate 7 was obtained, and the target compounds of 2-amido-1-arylethanols and 2-sulfonamido-1-arylethanols were synthesized by acylation, reduction and debenzylation of intermediate 7 and acyl chlorides containing different substituents.The structures of target compounds were confirmed by ESI-MS and 1H-NMR.The preliminary biological activity evaluation tests in vitro showed that the ECvalue of compounds 10 b and 10 h were 0.96 μmol·L^(-1)and 0.60 μmol·L^(-1),respectively.
作者
伊策
葛新月
潘莉
程卯生
YI Ce;GE Xin-yue;PAN Li;CHENG Mao-sheng(Key Laboratory of Structure-Based Drug Design and Discovery(Shenyang Pharmaceutical University),Ministry of Education,Shenyang 110016,China)
出处
《中国药物化学杂志》
CAS
CSCD
2022年第8期581-589,共9页
Chinese Journal of Medicinal Chemistry
基金
国家自然科学基金项目(81872752)。
