| 1. |
- Johannesson, Petra, et al.
(författare)
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SAR and optimization of trioxoisothiazole-based liver receptor X (LXR) agonists leading to the clinical candidate AZD3971
- 2014
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Ingår i: Division of Medicinal Chemistry. ; , s. 247-247
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Konferensbidrag (refereegranskat)abstract
- The liver X receptors (LXRα and LXRβ) are members of the nuclear receptor family of transcription factors. The activation of LXR induces genes involved in reverse cholesterol transport (RCT), which is believed to be the main effect of LXR agonists in the prevention or treatment of atherosclerosis. However LXR agonists have also been shown to cause hepatic steatosis and hypertriglyceridaemia. The ability to separate beneficial effects from negative effects has been a challenge that so far has hampered the development of LXR agonists for human use. We herein describe the SAR and optimization of a series of trioxoisothiazole-based LXR agonists leading to compounds with nanomolar potencies and a separation of beneficial versus negative effects in vivo. This work ultimately led to the nomination of AZD3971 as a candidate for the treatment of atherosclerosis.
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| 2. |
- Pemberton, Nils, et al.
(författare)
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Synthesis and Functionalization of Cyclic Sulfonimidamides : A Novel Chiral Heterocyclic Carboxylic Acid Bioisostere
- 2012
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Ingår i: ACS Medicinal Chemistry Letters. - : American Chemical Society (ACS). - 1948-5875. ; 3:7, s. 574-578
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Tidskriftsartikel (refereegranskat)abstract
- An efficient synthesis of aryl substituted cyclic sulfonimidamides designed as chiral nonplanar heterocyclic carboxylic acid bioisosteres is described. The cyclic sulfonimidamide ring system could be prepared in two steps from a trifluoroacetyl protected sulfinamide and methyl ester protected amino acids. By varying the amino acid, a range of different C-3 substituted sulfonimidamides could be prepared. The compounds could be further derivatized in the aryl ring using standard cross coupling reactions to yield highly substituted cyclic sulfonimidamides in excellent yields. The physicochemical properties of the final compounds were examined and compared to those of the corresponding carboxylic acid and tetrazole derivatives. The unique nonplanar shape in combination with the relatively strong acidity (pK(a) 5-6) and the ease of modifying the chemical structure to fine-tune the physicochemical properties suggest that this heterocycle can be a valuable addition to the range of available carboxylic acid isosteres.
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| 3. |
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| 4. |
- Adams, Emma Catherine, et al.
(författare)
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The structure-function relationship for alumina supported platinum during the formation of ammonia from nitrogen oxide and hydrogen in the presence of oxygen
- 2016
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Ingår i: Physical Chemistry Chemical Physics. - : Royal Society of Chemistry (RSC). - 1463-9076 .- 1463-9084. ; 18:16, s. 10850-10855
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Tidskriftsartikel (refereegranskat)abstract
- We study the structure-function relationship of alumina supported platinum during the formation of ammonia from nitrogen oxide and dihydrogen by employing in situ X-ray absorption and Fourier transform infrared spectroscopy. Particular focus has been directed towards the effect of oxygen on the reaction as a model system for emerging technologies for passive selective catalytic reduction of nitrogen oxides. The suppressed formation of ammonia observed as the feed becomes net-oxidizing is accompanied by a considerable increase in the oxidation state of platinum as well as the formation of surface nitrates and the loss of NH-containing surface species. In the presence of (excess) oxygen, the ammonia formation is proposed to be limited by weak interaction between nitrogen oxide and the oxidized platinum surface. This leads to a slow dissociation rate of nitrogen oxide and thus low abundance of the atomic nitrogen surface species that can react with the adsorbed hydrogen species. In this case the consumption of hydrogen through the competing water formation reaction and decomposition/oxidation of ammonia are of less importance for the net ammonia formation.
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| 5. |
- Adams, Emma, 1989, et al.
(författare)
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Structure-function relationship for alumina supported platinum during formation of ammonia from nitrogen oxide and hydrogen in presence of oxygen
- 2016
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Ingår i: Physical Chemistry Chemical Physics. - 1463-9084 .- 1463-9076. ; 18:16, s. 10850-10855
-
Tidskriftsartikel (refereegranskat)abstract
- We study the structure-function relationship of alumina supported platinum during forma- tion of ammonia from nitrogen oxide and dihydrogen by employing in situ X-ray absorption and Fourier transformed infrared spectroscopy. Particular focus is directed towards the effect of increased levels of oxygen on the reaction as a model system for emerging technologies for passive selective catalytic reduction of nitrogen oxides. The suppressed formation of ammo- nia observed as the feed becomes net-oxidizing is accompanied by a considerable increase in the oxidation state of platinum as well as enhanced formation of surface nitrates and loss of NH-containing surface species. In the presence of (excess) oxygen, the ammonia formation is proposed to be limited by the weak interaction between nitrogen oxide and the oxidized platinum surface. This leads to slow dissociation rate of nitrogen oxide and thus low abun- dance of atomic nitrogen surface species that can react with adsorbed hydrogen atoms. In this case the consumption of hydrogen through the competing water formation reaction and decomposition/oxidation of ammonia are of less importance for the net ammonia formation.
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| 6. |
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| 7. |
- Ekman, Inger, 1959-
(författare)
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Självskadande handlingar : ungdomars berättelser: kontextualisering av ett medikaliserat socialt fenomen
- 2018
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The aim of this thesis is twofold; to explore adolescents’ own views on self-injuring acts and to analyse the field of research on self-injuring acts. Together, these two aims comprise the overall aim of the thesis; to increase knowledge on self-injuring acts among adolescents.The material for the first study consists of scientific publications from 1913 to 2018. The material for the three following studies consists of adolescents’ Internet published unsolicited first-person narratives on their experience of self-injuring acts.Based on an examination of the research literature over a hundred year period, it was found that self-injuring acts have been medicalized since the beginning of research. Studies in the 1960’s and 1970’s were mainly conducted through observations of female psychiatric inpatients, establishing a picture of the typical cutter as a young, attractive, emotionally unstable woman. Although later research has found self-injuring acts to be common among community adolescents, the dominance of medical and psychological studies has continued to reinforce the view on self-injuring acts as related to intrapersonal difficulties.In the narratives studied, the adolescents described their self-injuring acts as closely related to an unstable social context, consisting of problems within the family, problems at school and the loss of dear ones. The recurrently described lack of access to an arena of comfort, a place or a relation providing trust and security, was found to be significant with respect to the initiation of self-injuring acts among these adolescents.In contrast to the common view on self-injuring acts as an outcome of individual characteristics, the findings point to adolescents’ self-injuring acts as a cognitively motivated and planned strategy to endure otherwise unbearable situations. Due to their adolescent position, their options to act, to take control or make changes are severely restricted.Disclosure of self-injuring acts within the social network was described as met with demands to seek professional mental help. Thoughts on seeking professional help were accompanied by fear of being perceived as crazy or diagnosed as mentally ill, thus causing social stigma. Thus, the medicalization of self-injuring acts was found to have negative consequences for disclosure and help-seeking, thereby limiting the adolescents’ options for finding adequate support. Internet websites were described as value-free and safe arenas, providing an opportunity to disclose self-injuring acts without fear of being stigmatized.The main conclusion is that adolescents’ self-injuring acts are closely related to problems in the social context, and need to be understood and related to the restrictions inherent in an adolescent position. From this perspective, it is the social context, not the self-injuring acts that should be in focus in research and practice. Social work research, focusing on social context and interaction, could develop the research field, broaden perspectives on these acts, and develop knowledge and understanding that goes beyond the established medicalized view of self-injuring acts.
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| 8. |
- Evertsson, Emma, et al.
(författare)
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A hierarchical screening approach to enantiomeric separation
- 2017
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Ingår i: Chirality. - : WILEY. - 0899-0042 .- 1520-636X. ; 29:5, s. 202-212
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Tidskriftsartikel (refereegranskat)abstract
- The screening of a number of chiral stationary phases (CSPs) with different modifiers in supercritical fluid chromatography to find a chromatographic method for separation of enantiomers can be time-consuming. Computational methods for data analysis were utilized to establish a hierarchical screening strategy, using a dataset of 110 drug-like chiral compounds with diverse structures tested on 15 CSPs with two different modifiers. This dataset was analyzed using a combinatorial algorithm, principal component analysis (PCA), and a correlation matrix. The primary goal was to find a set of eight columns resolving a large number of compounds, but also having complementary enantioselective properties. In addition to the hereby defined hierarchical experimental strategy, quantitative structure enantioselective models (QSERs) were evaluated. The diverse chemical space and relatively limited size of the training set reduced the accuracy of the QSERs. However, including separation factors from other CSPs increased the accuracies of the QSERs substantially. Hence, such combined models can support the experimental strategy in prioritizing the CSPs of the second screening phase, when a compound is not separated by the primary set of columns.
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| 9. |
- Giordanetto, Fabrizio, et al.
(författare)
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Discovery of cyclopentane- and cyclohexane-trans-1,3-diamines as potent melanin-concentrating hormone receptor 1 antagonists
- 2007
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Ingår i: Bioorganic & Medicinal Chemistry Letters. - : Elsevier BV. - 0960-894X. ; 17:15, s. 4232-41
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Tidskriftsartikel (refereegranskat)abstract
- We herein report the optimization of cyclopentane- and cyclohexane-1,3-diamine derivatives as novel and potent MCH-R1 antagonists. Structural modifications of the 2-amino-quinoline and thiophene moieties found in the initial lead compound served to improve its metabolic stability profile and MCH-R1 affinity, and revealed unprecedented SAR when compared to other 2-amino-quinoline-containing MCH-R1 antagonists.
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| 10. |
- Zetterberg, Johan, et al.
(författare)
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Spatially and temporally resolved gas distributions around heterogeneous catalysts using infrared planar laser-induced fluorescence.
- 2015
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- Visualizing and measuring the gas distribution in close proximity to a working catalyst is crucial for understanding how the catalytic activity depends on the structure of the catalyst. However, existing methods are not able to fully determine the gas distribution during a catalytic process. Here we report on how the distribution of a gas during a catalytic reaction can be imaged in situ with high spatial (400 μm) and temporal (15 μs) resolution using infrared planar laser-induced fluorescence. The technique is demonstrated by monitoring, in real-time, the distribution of carbon dioxide during catalytic oxidation of carbon monoxide above powder catalysts. Furthermore, we demonstrate the versatility and potential of the technique in catalysis research by providing a proof-of-principle demonstration of how the activity of several catalysts can be measured simultaneously, either in the same reactor chamber, or in parallel, in different reactor tubes.
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