6149-22-0Relevant academic research and scientific papers
Phthalazinones. Part 1: The design and synthesis of a novel series of potent inhibitors of poly(ADP-ribose)polymerase
Loh Jr., Vincent M.,Cockcroft, Xiao-Ling,Dillon, Krystyna J.,Dixon, Lesley,Drzewiecki, Jan,Eversley, Penny J.,Gomez, Sylvie,Hoare, Janet,Kerrigan, Frank,Matthews, Ian T.W.,Menear, Keith A.,Martin, Niall M.B.,Newton, Roger F.,Paul, Jane,Smith, Graeme C.M.,Vile, Julia,Whittle, Alan J.
, p. 2235 - 2238 (2007/10/03)
Screening of the Maybridge compound collection identified 4-arylphthalazinones as micromolar inhibitors of PARP-1 catalytic activity. Subsequent optimisation of both inhibitory activity and metabolic stability led to a novel series of meta-substituted 4-benzyl-2H-phthalazin-1-ones with low nanomolar, cellular activity as PARP-1 inhibitors and promising metabolic stability in vitro.
PHTHALAZINONE DERIVATIVES
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Page/Page column 64, (2008/06/13)
A compound of formula (I); or an isomer, salt, solvate, chemically protected form, or prodrug thereof, wherein A and B together represent an optionally substituted, fused aromatic ring; RL is a C5-7aryl group substituted in the meta position by the group R2, and optionally further substituted; wherein R2 is selected from formula (II) and formula (III); and its use as a pharmaceutical, in particular for the treatment of diseases ameliorated by inhibiting the activity of PARP
Reactions of Carbonyl Compounds in Basic Solutions. Part 9. Methoxide-catalysed Cyclization of Benzylidenephthalides and Methyl o-Phenylacetylbenzoates
Bowden, Keith,Chehel-Amiran, Mohsen
, p. 2031 - 2034 (2007/10/02)
The detailed mechanism of the methoxide-catalysed rearrangement of substituted benzylidenephthalides and both normal and pseudo methyl o-phenylacetylbenzoates to form 2-phenylindane-1,3-diones has been studied.A rate-acidity function correlation for the reactions in methanolic dimethyl sulphoxide (DMSO) shows a linear increase in rate with increasing H- to reach a maximum in rate before decreasing, except for the p-nitro substrate.This derivative shows a rate decrease throughout the H- range.The ρ values in methanol and in 94 mol percent methanolic DMSO are 1.7 and -1.6, respectively.The kinetic isotope effect has been observed with kH/kD 0.8-1.0.The equilibrium constants for ring-chain tautomerism of the methyl o-phenylacetylbenzoates have been determined and shown to be independent of substituent and solvent composition.The rate-determining step is the intramolecular attack of the anion of the normal ester on the ester carbonyl group.In methanol and methanolic DMSO of high methanol content this is preceded by the ionization equilibrium of the normal ester.In methanolic DMSO of low methanol content and for the p-nitro substrate, the initial state is the anion itself.
