Additional file 1: Table S1. of Impact of pulmonary exposure to gold core silver nanoparticles of different size and capping agents on cardiovascular injury

Mean Serum Concentration of Selected Cytokines Post IT instillation of Citrate Capped AgNP. Table S2. Mean Serum Concentration of Selected Cytokines Post IT instillation of PVP Capped AgNP. (DOCX 27 kb

Identification of Neuropeptide S Antagonists: Structure–Activity Relationship Studies, X‑ray Crystallography, and in Vivo Evaluation

Modulation of the neuropeptide S (NPS) system has been linked to a variety of CNS disorders such as panic disorder, anxiety, sleeping disorders, asthma, obesity, PTSD, and substance abuse. In this study, a series of diphenyltetrahydro-1<i>H</i>-oxazolo­[3,4-α]­pyrazin-3­(5<i>H</i>)-ones were synthesized and evaluated for antagonist activity at the neuropeptide S receptor. The absolute configuration was determined by chiral resolution of the key synthetic intermediate, followed by analysis of one of the individual enantiomers by X-ray crystallography. The <i>R</i> isomer was then converted to a biologically active compound (<b>34</b>) that had a <i>K</i>_e of 36 nM. The most potent compound displayed enhanced aqueous solubility compared with the prototypical antagonist SHA-68 and demonstrated favorable pharmacokinetic properties for behavioral assessment. In vivo analysis in mice indicated a significant blockade of NPS induced locomotor activity at an ip dose of 50 mg/kg. This suggests that analogs having improved drug-like properties will facilitate more detailed studies of the neuropeptide S receptor system

TableS10-PropertiesandEstimates-2017-12-11

Estimated TK properties (e.g., Volume of Distribution, Fraction bioavailable) for in vivo rat studies

TableS9-InVivoData-2017-12-11

Plasma concentration vs. time toxicokinetic data collected for a variety of chemicals in Sprague-Dawley rat

TableS11-TKSummaryStats-2017-12-11

Model TK statistics (Cmax, AUC) for in vivo rat studies