Discovery and Synthesis of Heterobifunctional Degraders of Rearranged during Transfection (RET) Kinase.

We describe the design, synthesis, and structure-activity relationship (SAR) of heterobifunctional RET ligand-directed degraders (LDDs) derived from three different second-generation RET inhibitors. These LDDs are composed of a target binding motif (TBM) that binds to the RET protein, a linker, and a cereblon binding motif (CBM) as the E3 ligase recognition unit. This led to the identification of a series of pyrazolopyridine-based heterobifunctional LDDs, as exemplified by compound .

Young People Talk About Digital Support for Mental Health: An Online Survey of 15-30-Year Olds in New Zealand.

Background: Mental distress is on the rise for young people, and there are high levels of unmet need for support. Increasingly, young people are engaging with online mechanisms of support to avoid cost and wait times; however, online support does have its limitations. We surveyed young people, 15-30 years of age, in Aotearoa New Zealand to explore their views of digital support for mental health.

Synthesis of diversely substituted quinazoline-2,4(1,3)-diones by cyclization of -butyl (2-cyanoaryl)carbamates.

The synthesis of diversely substituted quinazoline-2,4(1,3)-diones by cyclization of -butyl (2-cyanoaryl)carbamates using readily accessible Boc protected -amino nitriles is reported. The reaction proceeds smoothly at room temperature using 1 equiv. of HO under basic conditions.

Organic Photoredox-Catalyzed -Trifluoromethylation of Aromatic and Heteroaromatic Thiols.

A visible-light-mediated trifluoromethylation protocol was developed for the conversion of (hetero)aromatic thiols to their respective -trifluoromethylated derivatives employing trifluoromethanesulfonyl chloride (CFSOCl) as a cost-effective source of trifluoromethyl radical (CF·) and a highly reducing organophotocatalyst, 3DPA2FBN. The developed methodology is operationally simple, providing access to a diverse range of products in up to 92% yield. A plausible mechanism has been postulated based on preliminary mechanistic studies, including irradiation on/off, UV-vis studies, and radical trapping experiments.