85-12-1Relevant articles and documents
Hydrolysis reactions of N-sulfonatooxy-N-acetyl-1-aminonaphthalene and N-sulfonatooxy-N-acetyl-2-aminonaphthalene: Limited correlation of nitrenium ion azide/solvent selectivities with mutagenicities of the corresponding amines
Novak, Michael,VandeWater, Amy J.,Brown, Angie J.,Sanzenbacher, Sarah A.,Hunt, Lori A.,Kolb, Brent A.,Brooks, Michael E.
, p. 6023 - 6031 (1999)
The hydrolysis reactions of the title compounds N-sulfonatooxy-N- acetyl-1-aminonaphthalene, 2d, and N-sulfonatooxy-N-acetyl-2- aminonaphthalene, 2e, in 5% CH3CN-H2O (20 °C, pH 5.7-7.5, μ = 0.5) appear to involve nitrenium ion intermediates that exhibit very small azide/solvent trapping efficiencies. The azide/solvent selectivities, S, were estimated from fitting azide- and solvent-derived product yields as a function of [N3- ]. The derived values of S for the N-acetyl-N-(1-naphthyl)-nitrenium ion (3d) of 0.7 ± 0.1 M-1 and the N-acetyl-N-(2-naphthyl)nitrenium ion (3e) of 1.5 ± 0.2 M-1 show that these ions have short lifetimes (ca. 10-10 s) in aqueous solution. In turn, these results suggest that the hydrolysis reactions of 2d and 2e should proceed, in part, through ion-pair and/or preassociation pathways. The decrease in the yield of the rearrangement products N-acetyl-1-amino-2-sulfonatooxynaphthalene, 6, and N-acetyl-2- amino-1-sulfonatooxynaphthalene, 11, with increasing [N3-] indicates that this is the case. Plots of log(mutagenicity) toward Salmonella typhimurium TA 98 and TA 100 for a series of polycyclic and monocyclic aromatic amines vs log(S) for ArNAc+ show that there is no general correlation of mutagenicity with nitrenium ion selectivity, but there does appear to be a limited correlation of these two quantities for five polycyclic amines for which there are reliable mutagenicity and nitrenium ion selectivity data. These results suggest that nitrenium ion selectivity is one of several factors that determines the mutagenicity of aromatic amines.
The relevance of Ki calculation for bi-substrate enzymes illustrated by kinetic evaluation of a novel lysine (K) acetyltransferase 8 inhibitor
Wapenaar, Hannah,van den Bosch, Thea,Leus, Niek G.J.,van der Wouden, Petra E.,Eleftheriadis, Nikolaos,Hermans, Jos,Hailu, Gebremedhin Solomon,Rotili, Dante,Mai, Antonello,D?mling, Alexander,Bischoff, Rainer,Haisma, Hidde J.,Dekker, Frank J.
supporting information, p. 480 - 486 (2017/05/22)
Histone acetyltransferases (HATs) are important mediators of epigenetic post-translational modifications of histones that play important roles in health and disease. A disturbance of these modifications can result in disease states, such as cancer or inflammatory diseases. Inhibitors of HATs (HATi) such as lysine (K) acetyltransferase 8 (KAT8), could be used to study the epigenetic processes in diseases related to these enzymes or to investigate HATs as therapeutic targets. However, the development of HATi is challenged by the difficulties in kinetic characterization of HAT enzymes and their inhibitors to enable calculation of a reproducible inhibitory potency. In this study, a fragment screening approach was used, enabling identification of 4-amino-1-naphthol, which potently inhibited KAT8. The inhibitor was investigated for enzyme inhibition using kinetic and calorimetric binding studies. This allowed for calculation of the Ki values for both the free enzyme as well as the acetylated intermediate. Importantly, it revealed a striking difference in binding affinity between the acetylated enzyme and the free enzyme, which could not be revealed by the IC50 value. This shows that kinetic characterization of inhibitors and calculation of Ki values is crucial for determining the binding constants of HAT inhibitors. We anticipate that more comprehensive characterization of enzyme inhibition, as described here, is needed to advance the field of HAT inhibitors.
Introduction of a hydroxy group at the para position and N-iodophenylation of N-arylamides using phenyliodine(III) bis(trifluoroacetate)
Itoh, Naoki,Sakamoto, Takeshi,Miyazawa, Etsuko,Kikugawa, Yasuo
, p. 7424 - 7428 (2007/10/03)
The reaction of anilides with phenyliodine(III) bis(trifluoroacetate) (PIFA) in trifluoroacetic acid (TFA), TFA-CHCl3, or hexafluoroisopropyl alcohol (HFIP) is described. When the acyl group of the anilide is highly electronegative, such as trifluoroacetyl, or the phenyl group is substituted with an electron-withdrawing group, the 4-iodophenyl group is transferred from PIFA to the amide nitrogen to afford acetyldiarylamines. On the other hand, when the acyl group contains an electron-donating function, such as 4-methoxyphenyl, or the phenyl group is substituted with an electron-donating group, a trifluoroacetoxy group is transferred to the para position of the anilide aromatic ring. This group is hydrolyzed during workup to produce the corresponding phenol.
