273221-75-3Relevant articles and documents
Alcohol-supported Cu-mediated 18F-fluorination of iodonium salts under “minimalist” conditions
Orlovskaya, Victoriya V.,Modemann, Daniel J.,Kuznetsova, Olga F.,Fedorova, Olga S.,Urusova, Elizaveta A.,Kolks, Niklas,Neumaier, Bernd,Krasikova, Raisa N.,Zlatopolskiy, Boris D.
, (2019/09/09)
In the era of personalized precision medicine, positron emission tomography (PET) and related hybrid methods like PET/CT and PET/MRI gain recognition as indispensable tools of clinical diagnostics. A broader implementation of these imaging modalities in clinical routine is closely dependent on the increased availability of established and emerging PET-tracers, which in turn could be accessible by the development of simple, reliable, and efficient radiolabeling procedures. A further requirement is a cGMP production of imaging probes in automated synthesis modules. Herein, a novel protocol for the efficient preparation of 18F-labeled aromatics via Cu-mediated radiofluorination of (aryl)(mesityl)iodonium salts without the need of evaporation steps is described. Labeled aromatics were prepared in high radiochemical yields simply by heating of iodonium [18F]fluorides with the Cu-mediator in methanolic DMF. The iodonium [18F]fluorides were prepared by direct elution of 18F? from an anion exchange resin with solutions of the corresponding precursors in MeOH/DMF. The practicality of the novel method was confirmed by the racemization-free production of radiolabeled fluorophenylalanines, including hitherto unknown 3-[18F]FPhe, in 22–69% isolated radiochemical yields as well as its direct implementation into a remote-controlled synthesis unit.
Identification of dipeptidyl nitriles as potent and selective inhibitors of cathepsin B through structure-based drug design
Greenspan,Clark,Tommasi,Cowen,McQuire,Farley,Van Duzer,Goldberg,Zhou,Du,Fitt,Coppa,Fang,Macchia,Zhu,Capparelli,Goldstein,Wigg,Doughty,Bohacek,Knap
, p. 4524 - 4534 (2007/10/03)
Cathepsin B is a member of the papain superfamily of cysteine proteases and has been implicated in the pathology of numerous diseases, including arthritis and cancer. As part of an effort to identify potent, reversible inhibitors of this protease, we examined a series of dipeptidyl nitriles, starting with the previously reported Cbz-Phe-NH-CH2CN (19, IC50 = 62 μM). High-resolution X-ray crystallographic data and molecular modeling were used to optimize the P1, P2, and P3 substituents of this template. Cathepsin B is unique in its class in that it contains a carboxylate recognition site in the S2′ pocket of the active site. Inhibitor potency and selectivity were enhanced by tethering a carboxylate functionality from the carbon α to the nitrile to interact with this region of the enzyme. This resulted in the identification of compound 10, a 7 nM inhibitor of cathepsin B, with excellent selectivity over other cysteine cathepsins.
