Taken together, USP7 is a promising therapeutic target and USP7 inhibitors hold promise as a new approach to cancer therapy.

Herein we disclose a scalable organo-catalytic direct arylation approach for the regio- and atroposelective synthesis of non-C2-symmetric 2,2′-dihydroxy-1,1′-binaphthalenes (BINOLs). In the presence of catalytic amounts of axially chiral phosphoric acids, phenols and naphthols are coupled with iminoquinones via a cascade process that involves sequential aminal formation, sigmatropic rearrangement, and rearomatization to afford enantiomerically enriched BINOL derivatives in good to excellent yields. Our studies suggest that the (local) symmetry of the initially formed aminal intermediate has a dramatic impact on the level of enantioinduction in the final product. Aminals with a plane of symmetry give rise to BINOL derivatives with significantly lower enantiomeric excess than unsymmetrical ones featuring a stereogenic center. Presumably asymmetric induction in the sigmatropic rearrangement step is significantly more challenging than during aminal formation. Sigmatropic rearrangement of the enantiomerically enriched aminal and subsequent rearomatization transfers the central chirality into axial chirality with high fidelity.

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Hybridization, a strategy based on the covalent fusion of two or more existing pharmacophores to create a single molecule with multiple mechanisms of action, represents an encourage approach in the development of new drugs with potential therapeutic application in several pathologies. Triazoles and quinolones occupy an important position in medicinal chemistry attribute to their various biological activities, so hybridization of these two pharmacophores may provide more effective candidates that might be able to prevent the drug resistance. This review outlines the biological activities of triazole–quinolone hybrids, and discusses their structure–activity relationship.

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The metabolic-level boundaries (MLB) hypothesis proposes that metabolic level mediates the relative influence of surface area (SA)- versus volume-related metabolic processes on the body-mass scaling of metabolic rate in organisms. The variation in the scaling of SA may affect how metabolic level affects the metabolic scaling exponent. This study aimed to determine the influence of increasing metabolic level at a higher temperature on the metabolic scaling exponent of the goldfish and determine the link between metabolic scaling exponents and SA parameters of both gills and body. The SA of gills and body and the resting metabolic rate (RMR) of the goldfish were assessed at 15°C and 25°C, and their mass scaling exponents were analyzed. The results showed a significantly higher RMR, with a lower scaling exponent, in the goldfish at a higher temperature. The SA of the gills and the total SA of the fish (TSA) were reduced with the increasing temperature. The scaling exponent of RMR () tended to be close to that of the TSA at a higher temperature. This suggests that temperature positively affects metabolic level but negatively affects The findings support the MLB hypothesis. The lower scaling exponent at a higher temperature can be alternatively explained as follows: the higher viscosity of cold water impedes respiratory ventilation and oxygen uptake and reduces metabolic rate more in smaller individuals than in larger individuals at lower temperature, thus resulting in a negative association between temperature and.

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The mechanisms of the single and double Mannich reactions between acetaldehyde and N‐Boc imines are clarified by density functional theory calculations. For single addition of Mannich reaction, the energy difference between the transition states of different configurations correspond to an enantiomeric excess value of 90.58% (without solvent) and 98.46% (in acetonitrile) in favor of the (S)‐configuration product. For bis‐addition of Mannich reaction, the calculated enantiomeric excess value is 95.02% (without solvent) and 98.57% (in acetonitrile) in favor of the (S, S)‐configuration product. These calculated results are in good agreement with the experimental results. The calculations clearly demonstrate that the hydrogen‐bonding determine the stereochemistry of the reactions. Copyright © 2012 John Wiley & Sons, Ltd.