Diazotization-Enabled Deaminative Late-Stage Functionalization of Primary Sulfonamides.

We, for the first time, disclosed a simple and efficient strategy for the late-stage functionalization of primary sulfonamides by diazotization, leading to sulfonyl chlorides, sulfonates, and complex sulfonamides. This protocol obviates the requirement for the prefunctionalization of sulfonamides. Its applicability is exemplified by the late-stage functionalization of sulfonamide-type drugs.

Comparing the effectiveness and safety of Sorafenib plus TACE with Apatinib plus TACE for treating patients with unresectable hepatocellular carcinoma: a multicentre propensity score matching study.

OBJECTIVE: Local combined systemic therapy has been an important method for the treatment of unresectable hepatocellular carcinoma (HCC).The purpose of this study was to compare the effectiveness and safety of transarterial chemoembolization (TACE) plus Sorafenib versus TACE plus Apatinib for treating patients with unresectable HCC. METHODS: The clinical data of patients with unresectable HCC who were treated with TACE plus Sorafenib or TACE plus Apatinib at 5 Chinese medical centers between January 2016 and December 2020 were retrospectively analyzed. Propensity score matching (PSM) was applied to reduce the bias from confounding factors. RESULTS: A total of 380 patients were enrolled, of whom 129 cases were treated with TACE plus Sorafenib and 251 cases with TACE plus Apatinib. After the 1:1 PSM, 116 pairs of patients were involved in this study. The results showed that the PFS and OS in the TACE-Sorafenib group were significantly longer than those in the TACE-Apatinib group (PFS: 16.79 ± 6.45 vs. 14.76 ± 6.98 months, P = 0.049; OS: 20.66 ± 6.98 vs. 17.69 ± 6.72 months, P = 0.013). However, the ORR in the TACE-Apatinib group was markedly higher than that in the TACE-Sorafenib group (70.69% vs. 56.03%, P = 0.021). There were more patients with adverse events (AEs) in the TACE-Apatinib group than those in the TACE-Sorafenib group before dose adjustment (87 vs. 63, P = 0.001); however, the number of patients who suffered from AEs was not significantly different between the two groups after the dose adjustment (62 vs. 55, P = 0.148). No treatment-related death was found in the two groups. Subgroup analysis revealed that patients with unresectable HCC could better benefit from regular doses than reduced doses (Sorafenib, 22.59 vs. 18.02, P < 0.001; Apatinib, 19.75 vs. 16.86, P = 0.005). CONCLUSION: TACE plus either Sorafenib or Apatinib could effectively treat patients with unresectable HCC, the safety of TACE plus Sorafenib was better. and the ORR of TACE plus Apatinib was higher.

Photocatalytic synthesis of azaheterocycle-fused piperidines and pyrrolidines via tandem difunctionalization of unactivated alkenes.

A variety of azaheterocycle-fused piperidines and pyrrolidines bearing CF3 and CHF2 functionalities were obtained using CF3SO2Na and CHF2SO2Na by visible light photocatalysis. This protocol involves a radical cascade cyclization via tandem tri- and difluoromethylation-arylation of pendent unactivated alkenes. Benzimidazole, imidazole, theophylline, purine, and indole serve as applicable anchors, thereby enriching the structural diversity of piperidine and pyrrolidine derivatives. This method features mild, additive-free and transition metal-free conditions.