30459-17-7Relevant articles and documents
PYRAZOLO[1,5-a]PYRIMIDIN-7(4H)-ONE INHIBITORS OF DYNEIN
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, (2021/07/17)
Pyrazolo[1,5-a]pyrimidin-7(4H)-ones of formula (I) inhibit intraflagellar transport and are useful as anticancer agents and as probes of the function of dynein-dependent systems.
Design, synthesis, and biological evaluation of aryl piperazines with potential as antidiabetic agents via the stimulation of glucose uptake and inhibition of NADH:ubiquinone oxidoreductase
Breen, C. J.,Devine, R.,Driver, R. B.,Findlay, J. B. C.,Kelada, M.,Kinsella, G. K.,Leonard, S.,Martin, D. S. D.,Stephens, J. C.,Walsh, J. M. D.
, (2020/07/08)
The management of blood glucose levels and the avoidance of diabetic hyperglycemia are common objectives of many therapies in the treatment of diabetes. An aryl piperazine compound 3a (RTC1) has been described as a promoter of glucose uptake, in part through a cellular mechanism that involves inhibition of NADH:ubiquinone oxidoreductase. We report herein the synthesis of 41 derivatives of 3a (RTC1) and a systematic structure-activity-relationship study where a number of compounds were shown to effectively stimulate glucose uptake in vitro and inhibit NADH:ubiquinone oxidoreductase. The hit compound 3a (RTC1) remained the most efficacious with a 2.57 fold increase in glucose uptake compared to vehicle control and micromolar inhibition of NADH:ubiquinone oxidoreductase (IC50 = 27 μM). In vitro DMPK and in vivo PK studies are also described, where results suggest that 3a (RTC1) would not be expected to provoke adverse drug-drug interactions, yet be readily metabolised, avoid rapid excretion, with a short half-life, and have good tissue distribution. The overall results indicate that aryl piperazines, and 3a (RTC1) in particular, have potential as effective agents for the treatment of diabetes.
Energy Transfer to Ni-Amine Complexes in Dual Catalytic, Light-Driven C-N Cross-Coupling Reactions
Kudisch, Max,Lim, Chern-Hooi,Thordarson, Pall,Miyake, Garret M.
supporting information, p. 19479 - 19486 (2019/12/25)
Dual catalytic light-driven cross-coupling methodologies utilizing a Ni(II) salt with a photocatalyst (PC) have emerged as promising methodologies to forge aryl C-N bonds under mild conditions. The recent discovery that the PC can be omitted and the Ni(II) complex directly photoexcited suggests that the PC may perform energy transfer (EnT) to the Ni(II) complex, a mechanistic possibility that has recently been proposed in other systems across dual Ni photocatalysis. Here, we report the first studies in this field capable of distinguishing EnT from electron transfer (ET), and the results are consistent with F?rster-type EnT from the excited state [Ru(bpy)3]Cl2 PC to Ni-amine complexes. The structure and speciation of Ni-amine complexes that are the proposed EnT acceptors were elucidated by crystallography and spectroscopic binding studies. With the acceptors known, quantitative F?rster theory was utilized to predict the ratio of quenching rate constants upon changing the PC, enabling selection of an organic phenoxazine PC that proved to be more effective in catalyzing C-N cross-coupling reactions with a diverse selection of amines and aryl halides.