Direct amination of aryl halides with ammonia.

The traditional homogeneous access to aromatic amine derivatives is a nucleophilic aromatic substitution of the corresponding aryl halides. The halogen atom is usually relatively inert to amination reaction unless it is activated by the presence of electron withdrawing groups. Consequently, there has been particular emphasis over the past decade on the synthesis of metal complexes that are active catalysts for the preparation of aromatic amines. This tutorial review focuses on the use of metal-based complexes for the direct amination of aryl halides with ammonia.

Structure-based design, synthesis, and biological evaluation of a series of novel and reversible inhibitors for the severe acute respiratory syndrome-coronavirus papain-like protease.

We describe here the design, synthesis, molecular modeling, and biological evaluation of a series of small molecule, nonpeptide inhibitors of SARS-CoV PLpro. Our initial lead compound was identified via high-throughput screening of a diverse chemical library. We subsequently carried out structure-activity relationship studies and optimized the lead structure to potent inhibitors that have shown antiviral activity against SARS-CoV infected Vero E6 cells. Upon the basis of the X-ray crystal structure of inhibitor 24-bound to SARS-CoV PLpro, a drug design template was created. Our structure-based modification led to the design of a more potent inhibitor, 2 (enzyme IC(50) = 0.46 microM; antiviral EC(50) = 6 microM). Interestingly, its methylamine derivative, 49, displayed good enzyme inhibitory potency (IC(50) = 1.3 microM) and the most potent SARS antiviral activity (EC(50) = 5.2 microM) in the series. We have carried out computational docking studies and generated a predictive 3D-QSAR model for SARS-CoV PLpro inhibitors.

Chemoenzymatic synthesis and antiviral evaluation of conformationally constrained and 3'-methyl-branched carbanucleosides using both enantiomers of the same building block.

Starting from both enantiomers of a readily available building block, a straightforward enantioselective approach to constrained 3'-methyl-2',3'-alpha-oxirane-fused and 3'-methyl-3',4'-alpha-oxirane-fused carbanucleosides bearing different purine base analogues is described. The title compounds were evaluated as potential antiviral agents against important viruses. None of the new compounds had significant antiviral activity at a concentration of 100 microg/mL, which was the highest concentration tested.