Synthesis and SAR of cis-1-benzoyl-1,2,3,4-tetrahydroquinoline ligands for control of gene expression in ecdysone responsive systems.
Synthesis and SAR of cis-1-benzoyl-1,2,3,4-tetrahydroquinoline ligands for control of gene expression in ecdysone responsive systems.
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DOI：
10.1016/s0960-894x(03)00317-2
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发表时间：
2003-06
影响因子：
2.7
通讯作者：
Howard C. Smith;Caitlin K. Cavanaugh;Jennifer L. Friz;C. S. Thompson;Jessica A. Saggers;E. Michelotti;J. García;C. Tice
中科院分区：
文献类型：
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作者：
Howard C. Smith;Caitlin K. Cavanaugh;Jennifer L. Friz;C. S. Thompson;Jessica A. Saggers;E. Michelotti;J. García;C. Tice
制备了35个顺式-1-苯甲酰基-2-甲基-4-（苯胺基）-1，2，3，4-四氢喹啉类化合物的文库。这些化合物在苯甲酰基环、苯氨基环的4-位和四氢喹啉环的6-位上具有各种取代基。测定化合物在经工程改造以表达来自埃及伊蚊的蜕皮激素受体的哺乳动物细胞系中引起蜕皮激素应答元件下游的报道基因表达的能力。一般而言，在苯甲酰基环的Meta位和对位具有小的亲脂性取代基并且在苯氨基环的4-位和四氢喹啉环的6-位具有氢或氟的化合物是最有效的。
A library of 35 cis-1-benzoyl-2-methyl-4-(phenylamino)-1,2,3,4-tetrahydroquinolines was prepared. The compounds bore various substitutuents on the benzoyl ring, at the 4-position of the phenylamino ring and at the 6-position of the tetrahydroquinoline ring. The compounds were assayed for their ability to cause expression of a reporter gene downstream of an ecdysone response element in a mammalian cell line engineered to express the ecdysone receptor from Aedes aegypti. In general, compounds with small lipophilic substituents at the meta and para-positions of the benzoyl ring and hydrogen or fluorine at the 4-position of the phenylamino ring and the 6-position of the tetrahydroquinoline ring were the most potent.