| 1. |
- Scott, James S., et al.
(författare)
-
Circumventing seizure activity in a series of G protein coupled receptor 119 (GPR119) agonists
- 2014
-
Ingår i: Journal of Medicinal Chemistry. - : American Chemical Society. - 0022-2623 .- 1520-4804. ; 57:21, s. 8984-8998
-
Tidskriftsartikel (refereegranskat)abstract
- Agonism of GPR119 is viewed as a potential therapeutic approach for the treatment of type II diabetes and other elements of metabolic syndrome. During progression of a previously disclosed candidate 1 through mice toxicity studies, we observed tonic-clonic convulsions in several mice at high doses. An in vitro hippocampal brain slice assay was used to assess the seizure liability of subsequent compounds, leading to the identification of an aryl sulfone as a replacement for the 3-cyano pyridyl group. Subsequent optimization to improve the overall profile, specifically with regard to hERG activity, led to alkyl sulfone 16. This compound did not cause tonic-clonic convulsions in mice, had a good pharmacokinetic profile, and displayed in vivo efficacy in murine models. Importantly, it was shown to be effective in wild-type (WT) but not GPR119 knockout (KO) animals, consistent with the pharmacology observed being due to agonism of GPR119.
|
|
| 2. |
- Wells, James, et al.
(författare)
-
Standardisation of magnetic nanoparticles in liquid suspension
- 2017
-
Ingår i: Journal of Physics D: Applied Physics. - : IOP Publishing. - 0022-3727 .- 1361-6463. ; 50:383003, s. 1-25
-
Tidskriftsartikel (refereegranskat)abstract
- Suspensions of magnetic nanoparticles offer diverse opportunities for technology innovation,spanning a large number of industry sectors from imaging and actuation based applicationsin biomedicine and biotechnology, through large-scale environmental remediation uses suchas water purification, to engineering-based applications such as position-controlled lubricantsand soaps. Continuous advances in their manufacture have produced an ever-growing rangeof products, each with their own unique properties. At the same time, the characterisation ofmagnetic nanoparticles is often complex, and expert knowledge is needed to correctly interpretthe measurement data. In many cases, the stringent requirements of the end-user technologiesdictate that magnetic nanoparticle products should be clearly defined, well characterised,consistent and safe; or to put it another way—standardised. The aims of this document areto outline the concepts and terminology necessary for discussion of magnetic nanoparticles,to examine the current state-of-the-art in characterisation methods necessary for the mostprominent applications of magnetic nanoparticle suspensions, to suggest a possible structurefor the future development of standardisation within the field, and to identify areas and topicswhich deserve to be the focus of future work items. We discuss potential roadmaps for thefuture standardisation of this developing industry, and the likely challenges to be encounteredalong the way.
|
|
