1,2,3,9b-Tetrahydro-5H-imidazo[2,1-a]isoindol-5-ones as a new class of respiratory syncytial virus (RSV) fusion inhibitors. Part 2: identification of BTA9881 as a preclinical candidate.

Respiratory syncytial virus (RSV) is a major cause of respiratory tract infections in infants, young children and adults. 1,2,3,9b-Tetrahydro-5H-imidazo[2,1-a]isoindol-5-ones with general structure 1 were previously identified as promising inhibitors of RSV targeting the fusion glycoprotein. In particular, the introduction of a nitrogen at the 8-position of the tricyclic core yielded lead compounds 2 and 3.

Design, synthesis and biological evaluation of α-substituted isonipecotic acid benzothiazole analogues as potent bacterial type II topoisomerase inhibitors.

The discovery and optimisation of a new class of benzothiazole small molecules that inhibit bacterial DNA gyrase and topoisomerase IV are described. Antibacterial properties have been demonstrated by activity against DNA gyrase ATPase and potent activity against Staphylococcus aureus, Enterococcus faecalis, Streptococcus pyogenes and Haemophilus influenzae. Further refinements to the scaffold designed to enhance drug-likeness included analogues bearing an α-substituent to the carboxylic acid group, resulting in excellent solubility and favourable pharmacokinetic properties.

Electrochemistry of ferrocenoyl beta-peptide monolayers on gold.

The electrochemistry of self-assembled monolayers (SAMs) on gold containing a lipoic acid linker, the beta-peptide sequence (beta(3)Val-beta(3)Ala-beta(3)Leu)(n) for n = 1, 2, and a terminal ferrocenyl group has been described for the first time. Circular dichroism (CD), NMR, and molecular modeling were used to evaluate the beta-peptide structure in solution, while the monolayer film organization and electron-transfer kinetics were evaluated by cyclic voltammetry, chronoamperometry (CA), and ellipsometry. The peptides were assembled from trifluoroethanol solutions, where they are linear (n = 1) or helical (n = 2) based on CD, NMR, ellipsometry, and modeling evidence.

Olefin cross-metathesis of a vinyl-terminated self-assembled monolayer (SAM) on Au(111): electrochemical study using a ferrocenyl redox center.

Self-assembled thiol monolayers bound to single-crystal Au(111) surfaces containing a terminal olefin have been prepared and used to monitor electrochemically the cross-metathesis (CM) between the surface and an olefin-terminated ferrocenyl (Fc) derivative from solution over time. Mixed SAM surfaces were prepared by first adsorbing a diluent for 2 days followed by the olefinic alkanethiol for known adsorption time intervals; three diluents of varying length were used. The oxidation peak areas from the voltammetry show the CM reaction yields a maximum amount of product at 100-150 min.

Synthesis of cyclic beta-amino acid esters from methionine, allylglycine, and serine.

Here we report a versatile ring-closing metathesis-based approach to 5-, 6-, and 7-membered cyclic beta-amino esters starting with simple and readily available building blocks-methionine, allylglycine, and serine-where the nature of the amino acid determines the size of the carbocyclic ring.