142356-35-2Relevant academic research and scientific papers
Cavitands as Reaction Vessels and Blocking Groups for Selective Reactions in Water
Masseroni, Daniele,Mosca, Simone,Mower, Matthew P.,Blackmond, Donna G.,Rebek, Julius
, p. 8290 - 8293 (2016)
The majority of reactions currently performed in the chemical industry take place in organic solvents, compounds that are generally derived from petrochemicals. To promote chemical processes in water, we examined the use of synthetic, deep water-soluble cavitands in the Staudinger reduction of long-chain aliphatic diazides (C8, C10, and C12). The diazide substrates are taken up by the cavitand in D2O in folded, dynamic conformations. The reduction of one azide group to an amine gives a complex in which the substrate is fixed in an unsymmetrical conformation, with the amine terminal exposed and the azide terminal deep and inaccessible within the cavitand. Accordingly, the reduction of the second azide group is inhibited, even with excess phosphine, and good yields of the monofunctionalized products are obtained. In contrast, the reduction of the free diazides in bulk solution yields diamine products.
Fluorescent Benzothiazinone Analogues Efficiently and Selectively Label Dpre1 in Mycobacteria and Actinobacteria
Sommer, Raphael,Neres, Joao,Piton, Jérémie,Dhar, Neeraj,Van Der Sar, Astrid,Mukherjee, Raju,Laroche, Thierry,Dyson, Paul J.,McKinney, John D.,Bitter, Wilbert,Makarov, Vadim,Cole, Stewart T.
, p. 3184 - 3192 (2018)
Benzothiazinones (BTZ) are highly potent bactericidal inhibitors of mycobacteria and the lead compound, BTZ043, and the optimized drug candidate, PBTZ169, have potential for the treatment of tuberculosis. Here, we exploited the tractability of the BTZ scaffold by attaching a range of fluorophores to the 2-substituent of the BTZ ring via short linkers. We show by means of fluorescence imaging that the most advanced derivative, JN108, is capable of efficiently labeling its target, the essential flavoenzyme DprE1, both in cell-free extracts and after purification as well as in growing cells of different actinobacterial species. DprE1 displays a polar localization in Mycobacterium tuberculosis, M. marinum, M. smegmatis, and Nocardia farcinica but not in Corynebacterium glutamicum. Finally, mutation of the cysteine residue in DprE1 in these species, to which BTZ covalently binds, abolishes completely the interaction with JN108, thereby highlighting the specificity of this fluorescent probe.
Non-Peptide Fibrinogen Receptor Antagonists. 2. Optimization of a Tyrosine Template as a Mimic for Arg-Gly-Asp
Egbertson, Melissa S.,Chang, Charles T.-C.,Duggan, Mark E.,Gould, Robert J.,Halczenko, Wasyl,et al.
, p. 2537 - 2551 (2007/10/02)
Inhibitors of platelet-fibrinogen binding offer an opportunity to interrupt the final, common pathway for platelet aggregation.Small molecule inhibitors of the platelet fibrinogen receptor GPIIb/IIIa were prepared and evaluated for their ability to prevent platelet aggregation.Compound 23m (L-700, 462/MK-383) inhibited in vitro platelet aggregation with an IC50 of 9 nM and demonstrated a selectivity of >24000-fold between platelet and human umbilical vein endothelial cell fibrinogen receptors.Dose-dependent inhibition of ex vivo platelet aggregation induced by ADP was achieved with iv infusions 0.1-10 μg/kg/min of 23m in anesthetized dogs, with 10 μg/kg/min completely inhibiting platelet aggregation during the entire 6 h infusion protocol.Platelet aggregatability returned rapidly after the termination of the 23m infusions.These features suggest that 23m may be useful in the treatment of arterial occlusive disorders.
