Thes electivei ncorporation of fluorinated motifs, in particularC F 2 FG (FG = af unctional group) and CF 2 Hg roups,i ntoo rganic compounds has attrracted increasing attention since organofluorine molecules are of the utmost importance in the areas of nuclear imaging,pharmaceutical, agrochemical, and material sciences.Avariety of synthetic approachesh as been employed in late-stage difluoroalkylationr eactions.V isible light photoredox catalysis for the production of CF 2 FG and CF 2 Hr adicalsh as providedamore sustainable alternative to other conventional radical-triggered reactions from the viewpoint of safety,c ost, availability,a nd "green"c hemistry.Awide range of difluoroalkylating reagents has been successfully implemented in these organic transformationsi nt he presence of transitionm etal complexes or organic photocatalysts.I nmost cases, upon excitation via visible light irradiation with fluorescent light bulbs or blue light-emitting diode (LED) lamps,t hese photocatalysts can act as both reductivea nd oxidative quenchers,t hus enabling the applicationo fe lectron-donoro re lectron-acceptor difluoroalkylating reagents for the generation of CF 2 FG andC F 2 Hr adicals.S ubsequent radical addition to substrates and additional organic transformations affordt he corresponding difluoroalkylatedd erivatives.T he presentr eview describes the distinct strategies for the transitionm etal-and organic-pho-tocatalyzed difluoroalkylation of ab road range of organic substrates by visible light irradiationr eported in the literature since 2014.

No abstract

Despite ag rowing interest in CHF 2 in medicinal chemistry,there is alackofefficient methods for the insertion of CHF 18 Fi nto druglike compounds.H erein described is ap hotoredoxf lowr eaction for 18 F-difluoromethylation of Nheteroaromatics that are widely used in medicinal chemistry. Following the two-step synthesis for anew 18 F-difluoromethylation reagent, the photoredoxreaction is completed within two minutes and proceeds by CÀHa ctivation, circumventing the need for pre-functionalizationo ft he substrate.T he method is operationally simple and affords straightforwarda ccess to radiolabeled N-heteroaromatics with high molar activity suitable for biological in vivo studies and clinical application.

The growth inhibitory activity of p53 tumor suppressor is tightly regulated by interaction with two negative regulatory proteins, murine double minute 2 (MDM2) and X (MDMX), which are overexpressed in about half of all human tumors. The elucidation of crystallographic structures of MDM2/MDMX complexes with p53 has been pivotal for the identification of several classes of inhibitors of the p53-MDM2/MDMX interaction. The present review provides in silico strategies and screening approaches used in drug discovery as well as an overview of the most relevant classes of small-molecule inhibitors of the p53-MDM2/MDMX interaction, their progress in pipeline, and highlights particularities of each class of inhibitors. Most of the progress made with high-throughput screening has led to the development of inhibitors belonging to the cis-imidazoline, piperidinone, and spiro-oxindole series. However, novel potent and selective classes of inhibitors of the p53-MDM2 interaction with promising antitumor activity are emerging. Even with the discovery of the 3D structure of complex p53-MDMX, only two small molecules were reported as selective p53-MDMX antagonists, WK298 and SJ-172550. Dual inhibition of the p53-MDM2/MDMX interaction has shown to be an alternative approach since it results in full activation of the p53-dependent pathway. The knowledge of structural requirements crucial to the development of small-molecule inhibitors of the p53-MDMs interactions has enabled the identification of novel antitumor agents with improved in vivo efficacy.

No abstract