Prodrug Strategies to Improve the Solubility of the HCV NS5A Inhibitor Pibrentasvir (ABT-530).

A research program to discover solubilizing prodrugs of the HCV NS5A inhibitor pibrentasvir (PIB) identified phosphomethyl analog and trimethyl-lock (TML) prodrug . The prodrug moiety is attached to a benzimidazole nitrogen atom via an oxymethyl linkage to allow for rapid and complete release of the drug for absorption following phosphate removal by intestinal alkaline phosphatase. These prodrugs have good hydrolytic stability properties and improved solubility compared to PIB, both in aqueous buffer (pH 7) and FESSIF (pH 5).

One-pot Unsymmetrical Ketone Synthesis Employing a Pyrrole-Bearing Formal Carbonyl Dication Linchpin Reagent.

A one-pot procedure for the synthesis of unsymmetrical ketones utilizing a pyrrole-bearing carbonyl linchpin reagent (carbonyl linchpin N,O-dimethylhydroxylamine pyrrole; CLAmP) is reported. In contrast to other carbonyl dielectrophile equivalents, CLAmP enables the synthesis of ketones from a variety of organolithium and Grignard reagents. The electrophilic nature of CLAmP enables the addition of less reactive as well as thermally unstable nucleophiles.

Dithiocarbamate-coated SERS substrates: sensitivity gain by partial surface passivation.

The surface-enhanced Raman scattering (SERS) activity of nanoporous gold (NPG) can be boosted by controlled surface passivation. The SERS activities of unfunctionalized NPG were first optimized by etching substrates with NaI/I(2) (triiodide) and using 2-mercaptopyridine (2-MP) as the probing analyte. Gains in analyte sensitivity were then achieved by passivating the superficial regions of the NPG substrates with dimethyldithiocarbamate (Me(2)DTC) while leaving the more recessed "hot spots" available for SERS detection.