Searching for "Greener" Bioequivalents of CF3 to Lower its Environmental Impact.

Considering the broad use of the trifluoromethyl functional group (-CF3) in medicinal chemistry and taking into account the recent concerns on the negative environmental effects of CF3 containing compounds, we are searching for "greener" alternatives. Thus, different chemical groups (i. e. iodide, fluoride, cyclopropyl, isopropyl, cyclobutyl, 3-oxetyl, 2-oxetyl, methylsulfide, pentafluorosulfide, methylsulfonyl and sulfonamide) have been considered as potential bioequivalents of -CF3 aiming to use them in compounds with therapeutic interest instead of the polyfluoride functionality. Different structural (molecular surface and volume) and physicochemical (electronic and lipophilic) aspects of the bioequivalent functionalities proposed have been theoretically calculated and compared to those of -CF3. Additionally, the corresponding phenyl derivatives carrying these functionalities have been purchased or prepared and their experimental lipophilicity (i. e. LogP) measured using shake-flask experiments and UV-vis spectroscopy.

A Tale of Two Proteases: MPro and TMPRSS2 as Targets for COVID-19 Therapies.

Considering the importance of the 2019 outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) resulting in the coronavirus disease 2019 (COVID-19) pandemic, an overview of two proteases that play an important role in the infection by SARS-CoV-2, the main protease of SARS-CoV-2 (MPro) and the host transmembrane protease serine 2 (TMPRSS2), is presented in this review. After summarising the viral replication cycle to identify the relevance of these proteases, the therapeutic agents already approved are presented. Then, this review discusses some of the most recently reported inhibitors first for the viral MPro and next for the host TMPRSS2 explaining the mechanism of action of each protease. Afterward, some computational approaches to design novel MPro and TMPRSS2 inhibitors are presented, also describing the corresponding crystallographic structures reported so far. Finally, a brief discussion on a few reports found some dual-action inhibitors for both proteases is given. This review provides an overview of two proteases of different origins (viral and human host) that have become important targets for the development of antiviral agents to treat COVID-19.

Green synthesis of nitroaryl thioureas: Towards an improved preparation of guanidinium DNA binders.

We present a general efficient green method for the preparation of nitro N,N'-diaryl thioureas via a one-pot method using cyrene as a solvent with almost quantitative yields. This confirmed the viability of cyrene as a green alternative to THF in the synthesis of thiourea derivatives. After screening different reducing conditions, the nitro N,N'-diaryl thioureas were selectively reduced using Zn dust in the presence of water and acid to the corresponding amino N,N'-diaryl thioureas. These were then used to test the installation of the Boc-protected guanidine group with N,N'-bis-Boc protected pyrazole-1-carboxamidine as a guanidylating reagent not requiring mercury(II) activation. Finally, the TFA salts obtained after Boc-deprotection of two sample compounds were tested for their affinity towards DNA showing no binding.