146830-22-0Relevant academic research and scientific papers
Discovery of quinolinediones exhibiting a heat shock response and angiogenesis inhibition
Hargreaves, Robert H. J.,David, Cynthia L.,Whitesell, Luke J.,LaBarbera, Daniel V.,Jamil, Akmal,Chapuis, Jean C.,Skibo, Edward B.
, p. 2492 - 2501 (2008/12/21)
A series of substituted quinoline-5,8-diones were synthesized and evaluated as inhibitors of the chaperone protein Hsp90 using two assays: competition for binding to C-terminal ATP-binding site and competition for binding to N-terminal ATP-binding site. I
Novel quinolinequinone antitumor agents: Structure-metabolism studies with NAD(P)H:quinone oxidoreductase (NQO1)
Fryatt, Tara,Pettersson, Hanna I.,Gardipee, Walter T.,Bray, Kurtis C.,Green, Stephen J.,Slawin, Alexandra M. Z.,Beall, Howard D.,Moody, Christopher J.
, p. 1667 - 1687 (2007/10/03)
A series of quinolinequinones bearing various substituents has been synthesized, and the effects of substituents on the metabolism of the quinones by recombinant human NAD(P)H:quinone oxidoreductase (hNQO1) was studied. A range of quinolinequinones were selected for study, and were specifically designed to probe the effects of aryl substituents at C-2. A range of 28 quinolinequinones 2-29 was prepared using three general strategies: the palladium(0) catalyzed coupling of 2-chloroquinolines, the classical Friedlaender synthesis and the double-Vilsmeier reaction of acetanilides. One example of an isoquinolinequinone 30 was also prepared, and the reduction potentials of the quinones were measured by cyclic voltammetry. For simple substituents R2 at the quinoline 2-position, the rates of quinone metabolism by hNQO1 decrease for R2=Cl>H～Me>Ph. For aromatic substituents, the rate of reduction decreases dramatically for R 2=Ph>1-naphthyl>2-naphthyl>4-biphenyl. Compounds containing a pyridine substituent are the best substrates, and the rates decrease as R 2=4-pyridyl>3-pyridyl>2-pyridyl>4-methyl-2-pyridyl>5- methyl-2-pyridyl. The toxicity toward human colon carcinoma cells with either no detectable activity (H596 or BE-WT) or high NQO1 activity (H460 or BE-NQ) was also studied in representative quinones. Quinones that are good substrates for hNQO1 are more toxic to the NQO1 containing or expressing cell lines (H460 and BE-NQ) than the NQO1 deficient cell lines (H596 and BE-WT).
Design of quinolinedione-based geldanamycin analogues
Hargreaves, Robert,David, Cynthia L.,Whitesell, Luke,Skibo, Edward B.
, p. 3075 - 3078 (2007/10/03)
Quinoline-5,8-dione-based compounds were designed from the structure of the geldanamycin-bound Hsp-90 active site. The active site model predicted that aromatic substituents should be present at the 2-position, to take advantage of a hydrophobic pocket, a
Incorporation of Quinoline-5,8-quinone Moiety into Polyaza Cavities
Thummel, Randolph P.,Chirayil, Sara,Hery, Christophe,Lim, Jean-Luc,Wang, Tie-Lin
, p. 1666 - 1671 (2007/10/02)
Silica gel supported nitric acid treatment of 2,5-dimethoxybenzaldehyde followed by reduction with iron powder provides 3,6-dimethoxy-2-aminobenzaldehyde.Friedlaender condensation of this species with a variety of ketones and diketones leads to 5,8-dimethoxyquinoline derivatives which may be oxidized by ceric ammonium nitrate (CAN) and pyridine-2,6-dicarboxylic acid N-oxide (PDANO) to the corresponding quinones.The quinone functionality can be incorporated into larger cavities by a selective stepwise Friedlaender approach and the CAN/PDANO oxidation appears to work preferentially for 5,8-dimethoxyquinoline.
