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1.	Barlind, Jonas G., et al. (author) Identification and design of a novel series of MGAT2 inhibitors 2013 In: Bioorganic & Medicinal Chemistry Letters. - : Elsevier BV. - 0960-894X .- 1464-3405. ; 23:9, s. 2721-2726 Journal article (peer-reviewed)abstract [Acyl CoA]monoacylglycerol acyltransferase 2 (MGAT2) is of interest as a target for therapeutic treatment of diabetes, obesity and other diseases which together constitute the metabolic syndrome. In this Letter we report our discovery and optimisation of a novel series of MGAT2 inhibitors. The development of the SAR of the series and a detailed discussion around some key parameters monitored and addressed during the lead generation phase will be given. The in vivo results from an oral lipid tolerance test (OLTT) using the MGAT2 inhibitor (S)-10, shows a significant reduction (68% inhibition relative to naive, p < 0.01) in plasma triacylglycerol (TAG) concentration.
2.	Barlind, Jonas G, et al. (author) Design and optimization of pyrazinecarboxamide-based inhibitors of diacylglycerol acyltransferase 1 (DGAT1) leading to a clinical candidate dimethylpyrazinecarboxamide phenylcyclohexylacetic acid (AZD7687) 2012 In: Journal of Medicinal Chemistry. - : American Chemical Society (ACS). - 0022-2623 .- 1520-4804. ; 55:23, s. 10610-10629 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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Type of publication: journal article (2)

Type of content: peer-reviewed (2)

Author/Editor: Barlind, Jonas G (2); Buckett, Linda K (2); Morentin Gutierrez, ... (2); Petersson, Annika U (2); Redzic, Alma (2); Vinblad, Johanna (1); show more...; Eriksson, Jan W. (1); Nordin, Andreas (1); Nilsson, Karolina (1); Bauer, Udo A (1); Birch, Alan M (1); Birtles, Susan (1); Butlin, Roger J (1); Davies, Robert D M (1); Hammond, Clare D (1); Hovland, Ragnar (1); Johannesson, Petra (1); Johansson, Magnus J (1); Kemmitt, Paul D (1); Lindmark, Bo T (1); Noeske, Tobias A (1); O'Donnell, Charles J (1); Turnbull, Andrew V (1); Crosby, Sharon G. (1); Davidsson, Ojvind (1); Emtenas, Hans (1); Ertan, Anne (1); Jurva, Ulrik (1); Lemurell, Malin (1); O'Mahony, Gavin (1); Wagberg, Fredrik (1); Yuan, Zhong-Qing (1); show less...

University: Uppsala University (1); Stockholm University (1)

Language: English (2)

Research subject (UKÄ/SCB): Natural sciences (1); Medical and Health Sciences (1)

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