Synthesis and SAR of cis-1-benzoyl-1,2,3,4-tetrahydroquinoline ligands for control of gene expression in ecdysone responsive systems.
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.
Smith
Howard C
HC
RHeoGene, PO Box 949, 727 Norristown Road, Spring House, PA 19477-0949, USA.
Cavanaugh
Caitlin K
CK
Friz
Jennifer L
JL
Thompson
Christine S
CS
Saggers
Jessica A
JA
Michelotti
Enrique L
EL
Garcia
Javier
J
Tice
Colin M
CM
D000330:Aedes / Q000378:metabolism; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004440:Ecdysone / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects*; D007536:Isomerism; D008024:Ligands; D011804:Quinolines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D011987:Receptors, Steroid / Q000187:drug effects / Q000378:metabolism; D013329:Structure-Activity Relationship; D015533:Transcriptional Activation / Q000187:drug effects
D008024:Ligands; D011804:Quinolines; D011987:Receptors, Steroid; C055469:ecdysone receptor; D004440:Ecdysone