Transforming Oxadiazolines through Nitrene Intermediates by Energy Transfer Catalysis: Access to Sulfoximines and Benzimidazoles.

Subtle differences in reaction conditions facilitated unprecedented photocatalytic reactions of oxadiazolines by energy transfer catalysis. A set of compounds, sulfoximines and benzimidazoles, were ingeniously prepared from oxadiazolines via nitrene intermediates by photocatalytic N-O/C-N bond cleavages. The synthesis of sulfoximines was realized through intermolecular N-S bond formation between nitrene intermediates and sulfoxides, whereas benzimidazoles were obtained via intramolecular aromatic substitution of the nitrene to the tethered aryl substituent.

Visible-Light-Induced Trifluoromethylation of Unactivated Alkenes with Tri(9-anthryl)borane as an Organophotocatalyst.

Tri(9-anthryl)borane was successfully applied as an organophotocatalyst for the visible-light-induced trifluoromethylation of unactivated alkenes with CF3I. The mild reaction conditions tolerated a variety of functional groups, and the reaction could be extended to perfluoroalkylations with C3F7I and C4F9I. Mechanistic studies revealed that the photoredox catalysis involves an oxidative quenching pathway.

The position of fluorine in CP-118,954 affects AChE inhibition potency and PET imaging quantification for AChE expression in the rat brain.

The in vitro inhibition potency against acetylcholinesterase (AChE) of fluorinated derivatives of CP-118,954 (1) has been shown to depend upon the position of aromatic fluorine (F) substitution on the N-benzyl moiety. Indeed, the meta-F-substituted compound 3 (IC50=1.4nM) shows similar potency with the parent compound 1 (IC50=1.2nM), whereas the ortho-F derivative 2 (IC50=3.2nM) and para-F derivative 4 (IC50=10.8nM) were found to be less potent AChE inhibitors. A comparative in vivo microdialysis study in rats showed that 3 has the strongest effect on the neuropharmacological properties as AChE inhibitor. For PET imaging studies, a radiolabeled ligand ([18F]3) was synthesized through nucleophilic aromatic substitution reaction of diaryliodonium salt-based aldehyde precursor followed by reductive alkylation in a two-step radiolabeling procedure with 11.5 ± 1.2% (n=24, non-decay corrected) radiochemical yield and over 99% radiochemical purity. In a comparative PET imaging study of the three 18F-containing derivatives of CP-118,954 ([18F]2-4), [18F]3 showed the highest radioactivity in the AChE-rich region of normal rat brain which visually reflected the in vitro AChE-binding affinity of 3. These findings support [18F]3 as a promising AChE-targeted PET imaging ligand for the assessment of cholinergic activity into the brain, providing also insights into the AChE ligand disposition, which depends upon the position of the aromatic fluorine in the benzyl moiety.

Synthesis and Evaluation of Tricarbonyl (99m)Tc-Labeled 2-(4-Chloro)phenyl-imidazo[1,2-a]pyridine Analogs as Novel SPECT Imaging Radiotracer for TSPO-Rich Cancer.

The 18-kDa translocator protein (TSPO) levels are associated with brain, breast, and prostate cancer progression and have emerged as viable targets for cancer therapy and imaging. In order to develop highly selective and active ligands with a high affinity for TSPO, imidazopyridine-based TSPO ligand (CB256, 3) was prepared as the precursor. (99m)Tc- and Re-CB256 (1 and 2, respectively) were synthesized in high radiochemical yield (74.5% ± 6.4%, decay-corrected, n = 5) and chemical yield (65.6%) by the incorporation of the [(99m)Tc(CO)3(H2O)3]⁺ and (NEt4)2[Re(CO)3Br3] followed by HPLC separation. Radio-ligand 1 was shown to be stable (>99%) when incubated in human serum for 4 h at 37 °C with a relatively low lipophilicity (logD = 2.15 ± 0.02). The rhenium-185 and -187 complex 2 exhibited a moderate affinity (Ki = 159.3 ± 8.7 nM) for TSPO, whereas its cytotoxicity evaluated on TSPO-rich tumor cell lines was lower than that observed for the precursor. In vitro uptake studies of 1 in C6 and U87-MG cells for 60 min was found to be 9.84% ± 0.17% and 7.87% ± 0.23% ID, respectively. Our results indicated that (99m)Tc-CB256 can be considered as a potential new TSPO-rich cancer SPECT imaging agent and provides the foundation for further in vivo evaluation.