Collaborative Virtual Screening Identifies a 2-Aryl-4-aminoquinazoline Series with Efficacy in an Model of Infection.

Probing multiple proprietary pharmaceutical libraries in parallel via virtual screening allowed rapid expansion of the structure-activity relationship (SAR) around hit compounds with moderate efficacy against , the causative agent of Chagas Disease. A potency-improving scaffold hop, followed by elaboration of the SAR via design guided by the output of the phenotypic virtual screening efforts, identified two promising hit compounds and , which were profiled further in pharmacokinetic studies and in an model of infection. Compound demonstrated clear reduction of parasitemia in the setting, confirming the interest in this series of 2-(pyridin-2-yl)quinazolines as potential anti-trypanosome treatments.

Collaborative virtual screening to elaborate an imidazo[1,2-]pyridine hit series for visceral leishmaniasis.

An innovative pre-competitive virtual screening collaboration was engaged to validate and subsequently explore an imidazo[1,2-]pyridine screening hit for visceral leishmaniasis. probing of five proprietary pharmaceutical company libraries enabled rapid expansion of the hit chemotype, alleviating initial concerns about the core chemical structure while simultaneously improving antiparasitic activity and selectivity index relative to the background cell line. Subsequent hit optimization informed by the structure-activity relationship enabled by this virtual screening allowed thorough investigation of the pharmacophore, opening avenues for further improvement and optimization of the chemical series.

In Vitro and In Silico Characterization of Lemborexant (E2006), a Novel Dual Orexin Receptor Antagonist.

Orexin (hypocretin) neuropeptides have, among others, been implicated in arousal/sleep control, and antagonizing the orexin signaling pathway has been previously demonstrated to promote sleep in animals and humans. This mechanism opens up a new therapeutic approach to curb excessive wakefulness in insomnia disorder rather than to promote sleep-related signaling. Here we describe the preclinical pharmacological in vitro and in silico characterization of lemborexant ((1,2)-2-{[(2,4-dimethylpyrimidin-5-yl)oxy]methyl}-2-(3-fluorophenyl)--(5-fluoropyridin-2-yl)cyclopropanecarboxamide)), a dual orexin receptor antagonist (DORA), as a novel experimental therapeutic agent for the symptomatic treatment of insomnia disorder and compare its properties to two other DORAs, almorexant and suvorexant.

[Analysis of aliphatic carboxylic acids in anaerobic digestion process waters by ion-exclusion chromatography].

The analysis of seven aliphatic carboxylic acids (formic, acetic, propionic, iso-butyric, n-butyric, iso-valeric and n-valeric acid) in anaerobic digestion process waters for biogas production was examined by ion-exclusion chromatography with dilute acidic eluents (benzoic acid, perfluorobutyric acid (PFBA) and sulfuric acid) and non-suppressed conductivity/ultraviolet (UV) detection. The columns used were a styrene/divinylbenzene-based strongly acidic cation-exchange resin column (TSKgel SCX) and a polymethacrylate-based weakly acidic cation-exchange resin column (TSKgel Super IC-A/C). Good separation was performed on the TSKgel SCX in shorter retention times.