WFRF:(Petersson Annika U.)
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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)
- Barlind, Jonas G (author)
- Bauer, Udo A (author)
- Birch, Alan M (author)
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- Birtles, Susan (author)
- Buckett, Linda K (author)
- Butlin, Roger J (author)
- Davies, Robert D M (author)
- Hammond, Clare D (author)
- Hovland, Ragnar (author)
- Johannesson, Petra (author)
- Johansson, Magnus J (author)
- Kemmitt, Paul D (author)
- Lindmark, Bo T (author)
- Morentin Gutierrez, Pablo (author)
- Noeske, Tobias A (author)
- Nordin, Andreas (author)
- O'Donnell, Charles J (author)
- Petersson, Annika U (author)
- Redzic, Alma (author)
- Turnbull, Andrew V (author)
- Vinblad, Johanna (author)
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- (creator_code:org_t)
- 2012-11-21
- 2012
- English.
- In: Journal of Medicinal Chemistry. - : American Chemical Society (ACS). - 0022-2623 .- 1520-4804. ; 55:23, s. 10610-10629
- Journal article (peer-reviewed)
Abstract
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- 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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- Barlind, Jonas G
- Bauer, Udo A
- Birch, Alan M
- Birtles, Susan
- Buckett, Linda K
- Butlin, Roger J
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- Davies, Robert D ...
- Eriksson, Jan W
- Hammond, Clare D
- Hovland, Ragnar
- Johannesson, Pet ...
- Johansson, Magnu ...
- Kemmitt, Paul D
- Lindmark, Bo T
- Morentin Gutierr ...
- Noeske, Tobias A
- Nordin, Andreas
- O'Donnell, Charl ...
- Petersson, Annik ...
- Redzic, Alma
- Turnbull, Andrew ...
- Vinblad, Johanna
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- Uppsala University
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