| 1. |
- Monticelli, Serena, et al.
(författare)
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Sustainable Asymmetric Organolithium Chemistry : Enantio- and Chemoselective Acylations through Recycling of Solvent, Sparteine, and Weinreb "Amine"
- 2019
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Ingår i: ChemSusChem. - : Wiley. - 1864-5631 .- 1864-564X. ; 12:6, s. 1147-1154
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Tidskriftsartikel (refereegranskat)abstract
- The well-established Hoppe-Beak chemistry, which involves enantioselective generation of organolithium compounds in the presence of (-)-sparteine, was revisited and applied to unprecedented acylations with Weinreb amides to access highly enantioenriched alpha-oxyketones and cyclic alpha-aminoketones. Recycling of the sustainable solvent cyclopentyl methyl ether, sparteine, and the released Weinreb amine [HNMe(OMe)] was possible through a simple work-up procedure that enabled full recovery of these precious materials. The methodology features a robust scope and flexibility, thus allowing the enantioselective preparation of scaffolds amenable of further derivatization.
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| 2. |
- Spreitzer, Iva, et al.
(författare)
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Pharmacokinetics of Novel Dopamine Transporter Inhibitor CE-123 and Modafinil with a Focus on Central Nervous System Distribution
- 2023
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Ingår i: International Journal of Molecular Sciences. - : MDPI. - 1661-6596 .- 1422-0067. ; 24:23
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Tidskriftsartikel (refereegranskat)abstract
- S-CE-123, a novel dopamine transporter inhibitor, has emerged as a potential candidate for cognitive enhancement. The objective of this study was to compare the tissue distribution profiles, with a specific focus on central nervous system distribution and metabolism, of S-CE-123 and R-modafinil. To address this objective, a precise liquid chromatography-high resolution mass spectrometry method was developed and partially validated. Neuropharmacokinetic parameters were assessed using the Combinatory Mapping Approach. Our findings reveal distinct differences between the two compounds. Notably, S-CE-123 demonstrates a significantly superior extent of transport across the blood-brain barrier (BBB), with an unbound brain-to-plasma concentration ratio (K-p,K-uu,K-brain) of 0.5, compared to R-modafinil's K-p,K-uu,K-brain of 0.1. A similar pattern was observed for the transport across the blood-spinal cord barrier. Concerning the drug transport across cellular membranes, we observed that S-CE-123 primarily localizes in the brain interstitial space, whereas R-modafinil distributes more evenly across both sides of the plasma membrane of the brain's parenchymal cells (K-p,K-uu,K-cell). Furthermore, our study highlights the substantial differences in hepatic metabolic stability, with S-CE-123 having a 9.3-fold faster metabolism compared to R-modafinil. In summary, the combination of improved BBB transport and higher affinity of S-CE-123 to dopamine transporters in comparison to R-modafinil makes S-CE-123 a promising candidate for further testing for the treatment of cognitive decline.
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| 3. |
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| 4. |
- Troosters, Thierry, et al.
(författare)
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Introduction of the harmonised respiratory physiotherapy curriculum
- 2019
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Ingår i: Breathe. - : European Respiratory Society (ERS). - 1810-6838 .- 2073-4735. ; 15:2, s. 110-115
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Forskningsöversikt (refereegranskat)abstract
- Building on the core syllabus for postgraduate training in respiratory physiotherapy, published in 2014, the European Respiratory Society (ERS) respiratory physiotherapy task force has developed a harmonised and structured postgraduate curriculum for respiratory physiotherapy training. The curriculum outlines the knowledge, skills and attitudes which must be mastered by a respiratory physiotherapist working with adult or paediatric patients, together with guidance for minimal clinical exposures, and forms of learning and assessment. This article presents the rationale, methodology and content of the ERS respiratory physiotherapy curriculum. The full curriculum can be found in the supplementary material.
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