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- Barlind, Jonas G, et al.
(author)
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Design and optimization of pyrazinecarboxamide-based inhibitors of diacylglycerol acyltransferase 1 (DGAT1) leading to a clinical candidate dimethylpyrazinecarboxamide phenylcyclohexylacetic acid (AZD7687)
- 2012
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In: Journal of Medicinal Chemistry. - : American Chemical Society (ACS). - 0022-2623 .- 1520-4804. ; 55:23, s. 10610-10629
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Journal article (peer-reviewed)abstract
- A new series of pyrazinecarboxamide DGAT1 inhibitors was designed to address the need for a candidate drug with good potency, selectivity, and physical and DMPK properties combined with a low predicted dose in man. Rational design and optimization of this series led to the discovery of compound 30 (AZD7687), which met the project objectives for potency, selectivity, in particular over ACAT1, solubility, and preclinical PK profiles. This compound showed the anticipated excellent pharmacokinetic properties in human volunteers.
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- Eccleshall, Sarah V., et al.
(author)
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Constraining the chronology of Pleistocene glaciations on Svalbard: Kapp Ekholm re-visited
- 2016
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In: Boreas. - : Wiley. - 0300-9483 .- 1502-3885. ; 45:4, s. 790-803
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Journal article (peer-reviewed)abstract
- © 2016 Collegium Boreas. Published by John Wiley & Sons LtdThe Kapp Ekholm site, in central Spitsbergen, shows alternating units of glaciomarine sandy silt and diamicton representing three glacial cycles and is key in reconstructing the Late Pleistocene glacial history of Svalbard. Part of the site is reinvestigated here by focusing on re-dating two units (B and F) interpreted as interglacial/interstadial glaciomarine deposits, in order to constrain the controversial chronology. A combination of Optical Stimulated Luminescence (OSL) on quartz, infrared stimulated luminescence with a 50°C readout temperature (IRSL50) and post infrared-infrared stimulated luminescence (pIR), both on feldspar, was applied. While Formation B was beyond the dateable range of OSL, IRSL50 and pIR ages lead to the conclusion that this unit represents the Last Interglacial, Marine Isotope Stage (MIS) 5e, and the underlying diamicton the MIS 6 glacial. Formation F yielded ages implying that the formation represents the MIS 5a interstadial and the underlying diamicton is interpreted to represent the MIS 5b stadial. This agrees with conclusions drawn concerning the Pleistocene glaciations elsewhere on Svalbard.
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