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Cyanoimines (C=N-CN) are eliciting increased attention because of their extensive presence in medicine and biologically active molecules. This study demonstrated the use of the electrochemical oxidative carbon-atom multifunctionalization and N-cyanation of imine to synthesize (Z)-N'-cyano-N-carbamimidothioate. This multicomponent reaction showed good step economy, thereby providing a tool to construct various cyanoimines. Moreover, good functional-group tolerance and large-scale synthesis were achieved under metal-free and external-oxidant-free conditions, indicating the potential applicability of this methodology. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to improve the intratumoral accumulation of an antibody-drug conjugate (ADC) and minimize its off-target toxicity, SKB264, a novel anti-trophoblast antigen 2 (TROP2) ADC that was developed using 2-methylsulfonyl pyrimidine as the linker to conjugate its payload (KL610023), a belotecan-derivative topoisomerase I inhibitor. The preclinical pharmacologic profiles of SKB264 were assessed in this study. Methods: The in vitro and in vivo pharmacologic profiles of SKB264, including efficacy, pharmacokinetics-pharmacodynamics (PK-PD), safety, and tissue distribution, were investigated using TROP2-positive cell lines, cell-derived xenograft (CDX), patient-derived xenograft (PDX) models, and cynomolgus monkeys. Moreover, some profiles were compared with IMMU-132. Results: In vitro, SKB264 and SKB264 monoclonal antibody (mAb) had similar internalization abilities and binding affinities to TROP2. After cellular internalization, KL610023 was released and inhibited tumor cell survival. In vivo, SKB264 significantly inhibited tumor growth in a dose-dependent manner in both CDX and PDX models. After SKB264 administration, the serum or plasma concentration/exposure of SKB264 (conjugated ADC, number of payload units ≥1), total antibody (Tab, unconjugated and conjugated mAb regardless of the number of the payload units), and KL610023 in cynomolgus monkeys increased proportionally with increasing dosage from 1 to 10 mg/kg. The linker stability of SKB264 was significantly enhanced as shown by prolonged payload half-life in vivo (SKB264 vs. IMMU-132, 56.3 h vs. 15.5 h). At the same dose, SKB264's exposure in tumor tissue was 4.6-fold higher than that of IMMU-132. Conclusions: Compared with IMMU-132, the longer half-life of SKB264 had a stronger targeting effect and better antitumor activity, suggesting the better therapeutic potential of SKB264 for treating TROP2-positive tumors. [ABSTRACT FROM AUTHOR]

This paper describes an efficient numerical approach for the calculation of the per-unit length earth-return impedance of a conductor inside a tunnel. The influence of the tunnel on the per-unit length impedance is replaced by a set of equivalent current sources via the fictitious medium method. The main advantage of the proposed approach is that it can solve the boundary value problem within the tunnel region. The proposed method can reduce the calculation region and, thus, leads to time savings. A comparison of the numerical results with published data shows very good agreement. The proposed method is a good candidate for impedance calculation of a conductor inside a tunnel. [ABSTRACT FROM AUTHOR]

In this paper, a simulation model is proposed to evaluate the electromagnetic transient surge current distribution in a lightning protection system (LPS) due to a direct lightning stroke. The model is based on the coupled transmission line network in the frequency domain combined with the Fourier transform technique. The conductor of the LPS is described using the coupled transmission line model, and can be reduced to an active two-port equivalent circuit. The unknown quantities are the node voltages of the LPS at the physical junction, which leads to a fast solver at each frequency. The validation of the proposed approach is performed by comparing the results with those in the technical literature. The numerical examples show the flexibility, efficiency, and accuracy of the model in the range of practical application of LPS. [ABSTRACT FROM AUTHOR]

A new highly catalytic enantioselective Michael addition of fluorobis(phenylsulfonyl)methane to α,β-unsaturated aldehydes has been developed for the preparation of chiral monofluoromethyl compounds under mild reaction conditions. [ABSTRACT FROM AUTHOR]