Preparation and study of a series of copolymers incorporating 2-vinyl-4,4-dimethylazlactone (VDMA) is reported. The reactivity ratios for photo-initiated free radical copolymerization of VDMA with methacrylic acid (MAA), acrylic acid (AA), acrylamide (AAm), dimethylacrylamide (DMAA), hydroxyethyl methacrylate (HEMA), methoxy poly(ethylene glycol) methacrylate (MPEG 300 MA), and 2-methacryloyloxyethyl phosphorylcholine (MPC), were determined by fitting comonomer conversion data obtained by in situ 1 H NMR to a terminal copolymerization equation. Semi-batch photo-copolymerizations were then used to synthesize the corresponding VDMA copolymers with constant composition. Their solubility and dissolution behavior, as well as their hydrolysis half-lives under physiological conditions, were determined. P(VDMA-co-MAA) copolymers with 52 to 93 mol % VDMA showed decreasing initial solubility and increasing hydrolysis half-lives with increasing VDMA content. VDMA copolymers with nonionic monomers AAm and DMAA were water soluble only at VDMA contents of 41 and 22 mol % or less, respectively, and showed longer hydrolysis half-lives than comparable MAA copolymers. VDMA copolymers with HEMA and MPEG 300 MA were found to crosslink during storage, so their hydrolysis half-lives were not determined. VDMA copolymers with 18% zwitterionic MPC showed a much longer half-life and superior initial solubility compared to analogous p(VDMAco-MAA), identifying this copolymer as a promising candidate for macromolecular crosslinkers in, for example, aqueous layerby-layer co-depositions with polyamines. V C 2012 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 50: [4674][4675][4676][4677][4678][4679][4680][4681][4682][4683][4684][4685] 2012

Acyclovir (ACV) and its derivatives have been highly effective for treating recurrent, lytic infections with Herpes Simplex Virus, type 1 (HSV-1), but searches for additional antiviral drugs are motivated by recent reports of resistance to ACV, particularly among immunocompromised patients. In addition, the relative neurotoxicity of ACV and its inability to prevent neurological sequelae among HSV-1 encephalitis survivors compel searches for new drugs to treat HSV-1 infections of the central nervous system (CNS). Primary drug screens for neurotropic viruses like HSV-1 typically utilize non-neuronal cell lines, but they may miss drugs that have neuron specific antiviral effects. Therefore, we compared the effects of a panel of conventional and novel anti-herpetic compounds in monkey epithelial (Vero) cells, human induced pluripotent stem cells (hiPSCs)-derived neural progenitor cells (NPCs) and hiPSC-derived neurons (N = 73 drugs). While the profiles of activity for the majority of the drugs were similar in all three tissues, Vero cells were less likely than NPCs to identify drugs with substantial inhibitory activity in hiPSC-derived neurons. We discuss the relative merits of each cell type for antiviral drug screens against neuronal infections with HSV-1.

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A novel method for the preparation of 2-carboxyl-3-aryl quinoline derivatives from anilines, ethyl glyoxalate and enol ethers as phenylacetaldehyde surrogates is reported. The three-component coupling reaction occurs rapidly under mild conditions in dichloromethane catalysed by TFA. The method allows a more direct access to 3-aryl quinolines, sidestepping issues encountered with phenylacetaldehyde derivatives. This chemistry was used to prepare quinolines with 3-diarylether functionality that showed low micromolar efficacy (IC50 range: 5-26 μM) against in vitro Toxoplasma gondii coupled with little or no cytotoxicity (TD50≥ 320 μM) towards the host cells.

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