Triazol: a privileged scaffold for proteolysis targeting chimeras.

Current traditional drugs such as enzyme inhibitors and receptor agonists/antagonists present inherent limitations due to occupancy-driven pharmacology as the mode of action. Proteolysis targeting chimeras (PROTACs) are composed of an E3 ligand, a connecting linker and a target protein ligand, and are an attractive approach to specifically knockdown-targeted proteins utilizing an event-driven mode of action. The length, hydrophilicity and rigidity of connecting linkers play important role in creating a successful PROTAC. Some PROTACs with a triazole linker have displayed promising anticancer activity. This review provides an overview of PROTACs with a triazole scaffold and discusses its structure-activity relationship. Important milestones in the development of PROTACs are addressed and a critical analysis of this drug discovery strategy is also presented.

Concise synthesis of 2-methoxyestradiol from 17ß-estradiol through the C(sp2)-H hydroxylation.

A four-step route for the synthesis of 2-methoxyestradiol (5) starting from 17ß-estradiol (1) has been achieved with a 51% overall yield. The key step was the ruthenium-catalyzed ortho-C(sp2)-H bond hydroxylation of aryl carbamates. Using dimethyl carbamate as the directing group, [RuCl2(p-cymene)]2 as the catalyst, PhI(OAc)2 as the oxidant and trifluoroacetate/trifluoroacetic anhydride (1:1) as the co-solvent, the hydroxyl group could be singly installed at the 2-position of 3-dimethylcarbamoyloxyestradiol (2) with 65% yield. Subsequent methylation of hydroxy and removal of dimethyl carbamate afforded 2-methoxyestradiol (5).

[Seasonal Effect of Simulated Nitrogen Deposition on Soil Respiration and Soil Enzyme Activity in Masson Pine Forest in Mt. Jinyun, Chongqing, China].

Soil enzymes involved in the conversion of soil carbon and nitrogen, meanwhile the availability of soil carbon and nitrogen is the base of soil enzymes, yet atmospheric N deposition influences the release of soil CO2 by reduce the activities of soil enzyme. The objective of this study was to investigate the effect of different nitrogen deposition on soil respiration and soil enzymes, and explore the relationship among soil respiration, soil temperature, soil moisture and soil enzymes in the Masson pine forest. The results might provide a reference for further study on the effects of nitrogen deposition on pine forest ecosystem. From May 2014 to July 2015, three nitrogen application treatments and a control treatment were set up: low nitrogen [N5, 20 g·(m2·a)-1], moderate nitrogen [N10, 40 g·(m2·a)-1], high nitrogen [N15, 60 g·(m2·a)-1] and control treatment [N0, 0 g·(m2·a)-1) in the Masson pine forest. We measured soil respiration, soil temperature, and soil moisture simultaneously by using the Automated Soil CO2 Exchange Station (ACE, UK). The results showed that: 1 Soil enzymes and soil respiration had obvious seasonal variation, soil respiration of N0, N5, N10 and N15 was the highest in Summer, followed by the Spring and Autumn, and the lowest in Winter, and no consistent change rule was found in soil enzymes. 2 Generally, nitrogen deposition suppressed soil respiration and soil enzymes, and these inhibitory effects were strengthened with increasing levels of nitrogen deposition. The only exception in which nitrogen deposition enhanced soil respiration was in the Masson pine forest in Winter, In Spring, Summer and Autumn, nitrogen deposition suppressed soil enzymes, while there was difference among Ure, Ive, CAT and ACP in Winter. 3 stepwise regression showed that in control treatment and low nitrogen treatment, T, Ure and Ive made great contributions to the Rs, and Rs rapidly increased with the increase of T, Ure and Ive. In middle nitrogen treatment, T, Ure and CAT made great contributions to the Rs, and Rs increased with the increase of T, Ure and CAT. In high nitrogen treatment, Rs decreased with the increase of Ure, yet Rs increased with the increase of CAT and W.