5 research outputs found
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>-oxazoloÂ[3,4-α]Âpyrazin-3Â(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><sub>e</sub> 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