130735-56-7Relevant articles and documents
Oxidative regioselective amination of chromones exposes potent inhibitors of the hedgehog signaling pathway
Samanta, Rajarshi,Narayan, Rishikesh,Bauer, Jonathan O.,Strohmann, Carsten,Sievers, Sonja,Antonchick, Andrey P.
, p. 925 - 928 (2015)
A transition metal-free, oxidative, regioselective cross-coupling between non-functionalized azoles and chromones at C2-position was developed. A broad reaction scope and further transformation of products were demonstrated. The biological evaluation of products revealed a novel class of hedgehog signaling pathway inhibitors. This journal is
Syntheses and Evaluation of 2- or 3-(N-Cyclicamino)chromone Derivatives as Monoamine Oxidase Inhibitors
Takao, Koichi,Sakatsume, Tsukasa,Kamauchi, Hitoshi,Sugita, Yoshiaki
, p. 1082 - 1089 (2020/11/26)
A series of 2-(N-cyclicamino)chromone derivatives (1a–4c) and 3-(N-cyclicamino)chromone derivatives (5a–8c) were synthesized, and their monoamine oxidase (MAO) A and B inhibitory activities were studied as part of a structure–activity relationship investigation. Compounds 1a–4c showed no remarkable inhibition for MAO-A or MAO-B, whereas compounds 5a–8c (with a few exceptions) showed significant and selective inhibition of MAO-B. Of these compounds, 7c, 7-methoxy-3-(4-phenyl-1-piperazinyl)-4H-1-benzopyran-4-one inhibited MAO-B the most potently and selectively, having IC50 of 15nM and an MAO-B selectivity index of more than 6700; c.f, 50nM and 2000, respectively, for safinamide. The mode of inhibition of 7c to MAO-B was competitive and reversible. Considering the IC50 values and selectivity indices of the other synthetic compounds, the presence of the methoxy group on the chromone ring (R2) of 7c seemed to increase MAO-B inhibition. Molecular docking analysis also supports this hypothesis. Our results suggest that 3-(N-cyclicamino)-chromones are useful lead compounds for the development of MAO-B inhibitors.
Selective benzopyranone and pyrimido[2,1-α]isoquinolin-4-one inhibitors of DNA-dependent protein kinase: Synthesis, structure-activity studies, and radiosensitization of a human tumor cell line in vitro
Griffin, Roger J.,Fontana, Gabriele,Golding, Bernard T.,Guiard, Sophie,Hardcastle, Ian R.,Leahy, Justin J. J.,Martin, Niall,Richardson, Caroline,Rigoreau, Laurent,Stockley, Martin,Smith, Graeme C. M.
, p. 569 - 585 (2007/10/03)
A diverse range of chromen-2-one, chromen-4-one and pyrimidoisoquinolin-4- one derivatives was synthesized and evaluated for inhibitory activity against the DNA repair enzyme DNA-dependent protein kinase (DNA-PK), with a view to elucidating structure-activity relationships for potency and kinase selectivity. DNA-PK inhibitory activity varied widely over the series of compounds evaluated (IC50 values ranged from 0.19 to >10 μM), with excellent activity being observed for the 7,8-benzochromen-4-one and pyrimido[2,1-a] isoquinolin-4-one templates. By contrast, inhibitors based on the benzochromen-2-one (coumarin) or 2-aryl-7,8-benzochromen-4-one (flavone) scaffolds were less potent. Crucially, these studies revealed a very constrained structure-activity relationship at the 2-position of the benzopyranone and pyrimido[2,1-a]-isoquinolin-4-one pharmacophore, with only a 2-morpholino or 2-(2′-methylmorpholino) group being tolerated at this position. More detailed biological studies conducted with the most potent inhibitor NU7163 (48; IC50 = 0.19 μM) demonstrated ATP-competitive DNA-PK inhibition, with a Ki value of 24 nM, and 48 exhibited selectivity for DNA-PK compared with the related enzymes ATM, ATR, mTOR, and PI 3-K (p110alpha). Compound 48 sensitized the HeLa human tumor cell line to the cytotoxic effects of ionizing radiation in vitro, a dose modification factor of 2.3 at 10% survival being observed with an inhibitor concentration of 5 μM. This study identified these structural classes as novel DNA-PK inhibitors and delineated initial structure-activity relationships against DNA-PK.
