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Grigory Veinberg Maxim Vorona Liga Zvejniece Reinis Vilskersts Edijs Vavers Edvards Liepinsh Helena Kazoka Sergey Belyakov Anatoly Mishnev Jevgenijs Kuznecovs Sergejs Vikainis Natalja Orlova Anton Lebedev Yuri Ponomaryov Maija Dambrova 《Bioorganic & medicinal chemistry》2013,21(10):2764-2771
Novel positive allosteric modulators of sigma-1 receptor represented by 2-(5-methyl-4-phenyl-2-oxopyrrolidin-1-yl)-acetamide enantiomers were synthesised using an asymmetric Michael addition of 2-nitroprop-1-enylbenzene to diethyl malonate. Following the chromatographic separation of the methyl erythro- and threo-4-nitro-3R- and 3S-phenylpentanoate diastereoisomers, target compounds were obtained by their reductive cyclisation into 5-methyl-4-phenylpyrrolidin-2-one enantiomers and the attachment of the acetamide group to the heterocyclic nitrogen. Experiments with electrically stimulated rat vas deference contractions induced by the PRE-084, an agonist of sigma-1 receptor, showed that (4R,5S)- and (4R,5R)-2-(5-methyl-4-phenyl-2-oxopyrrolidin-1-yl)-acetamides with an R-configuration at the C-4 chiral centre in the 2-pyrrolidone ring were more effective positive allosteric modulators of sigma-1 receptor than were their optical antipodes. 相似文献
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Peter Alexander Reinhard Prestele Peter H. Verburg Almut Arneth Claudia Baranzelli Filipe Batista e Silva Calum Brown Adam Butler Katherine Calvin Nicolas Dendoncker Jonathan C. Doelman Robert Dunford Kerstin Engström David Eitelberg Shinichiro Fujimori Paula A. Harrison Tomoko Hasegawa Petr Havlik Sascha Holzhauer Florian Humpenöder Chris Jacobs‐Crisioni Atul K. Jain Tamás Krisztin Page Kyle Carlo Lavalle Tim Lenton Jiayi Liu Prasanth Meiyappan Alexander Popp Tom Powell Ronald D. Sands Rüdiger Schaldach Elke Stehfest Jevgenijs Steinbuks Andrzej Tabeau Hans van Meijl Marshall A. Wise Mark D. A. Rounsevell 《Global Change Biology》2017,23(2):767-781
Understanding uncertainties in land cover projections is critical to investigating land‐based climate mitigation policies, assessing the potential of climate adaptation strategies and quantifying the impacts of land cover change on the climate system. Here, we identify and quantify uncertainties in global and European land cover projections over a diverse range of model types and scenarios, extending the analysis beyond the agro‐economic models included in previous comparisons. The results from 75 simulations over 18 models are analysed and show a large range in land cover area projections, with the highest variability occurring in future cropland areas. We demonstrate systematic differences in land cover areas associated with the characteristics of the modelling approach, which is at least as great as the differences attributed to the scenario variations. The results lead us to conclude that a higher degree of uncertainty exists in land use projections than currently included in climate or earth system projections. To account for land use uncertainty, it is recommended to use a diverse set of models and approaches when assessing the potential impacts of land cover change on future climate. Additionally, further work is needed to better understand the assumptions driving land use model results and reveal the causes of uncertainty in more depth, to help reduce model uncertainty and improve the projections of land cover. 相似文献
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