Carbodiimide that was generated from the condensation reaction of iminophosphorane with phenylisocyanate was allowed to react with different phosphorus nucleophiles. Thus, the in situ resulted heterocumulene reacted with dialkylhydrogenphosphonates in tetrahydrofuran (THF)/FeCl(3) /H(2) O system to give fused pyrrole- (≈14%) and pyrimidinephosphonates (≈57%). On the other hand, with tris-(dialkyl)aminophosphines, the reaction afforded the corresponding hexaalkylphosphinic diamides as a water-sensitive fine powder, quite stable for a few days in a desiccator. When a protonating agent was present in the reaction medium, the reaction was markedly accelerated leading to the formation of the phosphamides. Next, some saturated and unsaturated Horner-Emmons reagents were applied in situ to the same carbodiimide to obtain more phosphorylated N-heterocycles. The analgesic and antiinflammatory activities of the newly synthesized compounds were investigated and showed significant activities. Finally, we further estimated the antitumor activity of five new phosphonates against four carcinoma cell lines.
The potential of computational models to identify new therapeutics and repurpose existing drugs has gained significance in recent times. The current ‘COVID-19′ pandemic caused by the new SARS CoV2 virus has affected over 200 million people and caused over 4 million deaths. The enormity and the consequences of this viral infection have fueled the research community to identify drugs or vaccines through a relatively expeditious process. The availability of high-throughput datasets has cultivated new strategies for drug development and can provide the foundation towards effective therapy options. Molecular modeling methods using structure-based or computer-aided virtual screening can potentially be employed as research guides to identify novel antiviral agents. This review focuses on in-silico modeling of the potential therapeutic candidates against SARS CoVs, in addition to strategies for vaccine design. Here, we particularly focus on the recently published SARS CoV main protease (Mpro) active site, the RNA-dependent RNA polymerase (RdRp) of SARS CoV2, and the spike S-protein as potential targets for vaccine development. This review can offer future perspectives for further research and the development of COVID-19 therapies via the design of new drug candidates and multi-epitopic vaccines and through the repurposing of either approved drugs or drugs under clinical trial.
A new class of C-glycosyl amino acids displaying a thiourea segment as a linker has been designed and synthesized by addition of peracetylated glycosylmethyl isothiocyanates to an amine-functionalized amino acid (N(alpha)-Fmoc-beta-amino-l-alanine). Three pairs of compounds with alpha- and beta-galacto, alpha- and beta-gluco, and alpha- and beta-manno configuration have been prepared with yields ranging between 70 and 75%. The orthogonal set of protective groups (O-acetyl in the carbohydrate moiety and N-Fmoc in the amino acid residue) makes these compounds suitable substrates for the co-translational modification of natural peptides. The couplings of model hydroxy-free and perbenzylated glycosylmethyl isothiocyanates with the above N(alpha)-Fmoc-beta-amino-l-alanine and the N(alpha)-Boc-protected analogue have been carried out as well, thus broadening the scope of the coupling reaction. Nevertheless, there are limitations of this isothiocyanate-amine coupling in complex systems, and these are briefly discussed.
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