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Improving metabolic stability and removing aldehyde oxidase liability in a 5-azaquinazoline series of IRAK4 inhibitors.

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Title: Improving metabolic stability and removing aldehyde oxidase liability in a 5-azaquinazoline series of IRAK4 inhibitors.
Authors: Degorce SL; Medicinal Chemistry, Research and Early Development, Oncology R&D, AstraZeneca, Boston, 35 Gatehouse Drive, Waltham, MA 02451, United States. Electronic address: sebastien.degorce@astrazeneca.com., Aagaard A; Discovery Sciences, R&D, AstraZeneca, Gothenburg, SE-431 83 Mölndal, Sweden., Anjum R; Bioscience, Research and Early Development, Oncology R&D, AstraZeneca, Boston, 35 Gatehouse Drive, Waltham, MA 02451, United States., Cumming IA; Medicinal Chemistry, Research and Early Development, Oncology R&D, AstraZeneca, Cambridge Science Park, Unit 310 Darwin Building, Cambridge CB4 0WG, United Kingdom., Diène CR; Medicinal Chemistry, Research and Early Development, Oncology R&D, AstraZeneca, Cambridge Science Park, Unit 310 Darwin Building, Cambridge CB4 0WG, United Kingdom., Fallan C; Medicinal Chemistry, Research and Early Development, Oncology R&D, AstraZeneca, Cambridge Science Park, Unit 310 Darwin Building, Cambridge CB4 0WG, United Kingdom., Johnson T; Medicinal Chemistry, Research and Early Development, Oncology R&D, AstraZeneca, Cambridge Science Park, Unit 310 Darwin Building, Cambridge CB4 0WG, United Kingdom., Leuchowius KJ; Discovery Sciences, R&D, AstraZeneca, Gothenburg, SE-431 83 Mölndal, Sweden., Orton AL; DMPK, Research and Early Development, Oncology R&D, AstraZeneca, Cambridge Science Park, Unit 310 Darwin Building, Cambridge CB4 0WG, United Kingdom., Pearson S; Medicinal Chemistry, Research and Early Development, Oncology R&D, AstraZeneca, Cambridge Science Park, Unit 310 Darwin Building, Cambridge CB4 0WG, United Kingdom., Robb GR; Medicinal Chemistry, Research and Early Development, Oncology R&D, AstraZeneca, Cambridge Science Park, Unit 310 Darwin Building, Cambridge CB4 0WG, United Kingdom., Rosen A; Bioscience, Research and Early Development, Oncology R&D, AstraZeneca, Boston, 35 Gatehouse Drive, Waltham, MA 02451, United States., Scarfe GB; DMPK, Research and Early Development, Oncology R&D, AstraZeneca, Cambridge Science Park, Unit 310 Darwin Building, Cambridge CB4 0WG, United Kingdom., Scott JS; Medicinal Chemistry, Research and Early Development, Oncology R&D, AstraZeneca, Cambridge Science Park, Unit 310 Darwin Building, Cambridge CB4 0WG, United Kingdom., Smith JM; Medicinal Chemistry, Research and Early Development, Oncology R&D, AstraZeneca, Cambridge Science Park, Unit 310 Darwin Building, Cambridge CB4 0WG, United Kingdom., Steward OR; Medicinal Chemistry, Research and Early Development, Oncology R&D, AstraZeneca, Cambridge Science Park, Unit 310 Darwin Building, Cambridge CB4 0WG, United Kingdom., Terstiege I; Medicinal Chemistry, R&I, R&D, AstraZeneca, Gothenburg, SE-431 83 Mölndal, Sweden., Tucker MJ; Medicinal Chemistry, Research and Early Development, Oncology R&D, AstraZeneca, Cambridge Science Park, Unit 310 Darwin Building, Cambridge CB4 0WG, United Kingdom., Turner P; Medicinal Chemistry, Research and Early Development, Oncology R&D, AstraZeneca, Cambridge Science Park, Unit 310 Darwin Building, Cambridge CB4 0WG, United Kingdom., Wilkinson SD; DMPK, Research and Early Development, Oncology R&D, AstraZeneca, Cambridge Science Park, Unit 310 Darwin Building, Cambridge CB4 0WG, United Kingdom., Wrigley GL; Medicinal Chemistry, Research and Early Development, Oncology R&D, AstraZeneca, Cambridge Science Park, Unit 310 Darwin Building, Cambridge CB4 0WG, United Kingdom., Xue Y; Discovery Sciences, R&D, AstraZeneca, Gothenburg, SE-431 83 Mölndal, Sweden.
Source: Bioorganic & medicinal chemistry [Bioorg Med Chem] 2020 Dec 01; Vol. 28 (23), pp. 115815. Date of Electronic Publication: 2020 Oct 15.
Publication Type: Journal Article
Journal Info: Publisher: Elsevier Science Country of Publication: England NLM ID: 9413298 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1464-3391 (Electronic) Linking ISSN: 09680896 NLM ISO Abbreviation: Bioorg Med Chem Subsets: MEDLINE
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  Data: <searchLink fieldCode="AU" term="%22Degorce+SL%22">Degorce SL</searchLink>; Medicinal Chemistry, Research and Early Development, Oncology R&D, AstraZeneca, Boston, 35 Gatehouse Drive, Waltham, MA 02451, United States. Electronic address: sebastien.degorce@astrazeneca.com.<br /><searchLink fieldCode="AU" term="%22Aagaard+A%22">Aagaard A</searchLink>; Discovery Sciences, R&D, AstraZeneca, Gothenburg, SE-431 83 Mölndal, Sweden.<br /><searchLink fieldCode="AU" term="%22Anjum+R%22">Anjum R</searchLink>; Bioscience, Research and Early Development, Oncology R&D, AstraZeneca, Boston, 35 Gatehouse Drive, Waltham, MA 02451, United States.<br /><searchLink fieldCode="AU" term="%22Cumming+IA%22">Cumming IA</searchLink>; Medicinal Chemistry, Research and Early Development, Oncology R&D, AstraZeneca, Cambridge Science Park, Unit 310 Darwin Building, Cambridge CB4 0WG, United Kingdom.<br /><searchLink fieldCode="AU" term="%22Diène+CR%22">Diène CR</searchLink>; Medicinal Chemistry, Research and Early Development, Oncology R&D, AstraZeneca, Cambridge Science Park, Unit 310 Darwin Building, Cambridge CB4 0WG, United Kingdom.<br /><searchLink fieldCode="AU" term="%22Fallan+C%22">Fallan C</searchLink>; Medicinal Chemistry, Research and Early Development, Oncology R&D, AstraZeneca, Cambridge Science Park, Unit 310 Darwin Building, Cambridge CB4 0WG, United Kingdom.<br /><searchLink fieldCode="AU" term="%22Johnson+T%22">Johnson T</searchLink>; Medicinal Chemistry, Research and Early Development, Oncology R&D, AstraZeneca, Cambridge Science Park, Unit 310 Darwin Building, Cambridge CB4 0WG, United Kingdom.<br /><searchLink fieldCode="AU" term="%22Leuchowius+KJ%22">Leuchowius KJ</searchLink>; Discovery Sciences, R&D, AstraZeneca, Gothenburg, SE-431 83 Mölndal, Sweden.<br /><searchLink fieldCode="AU" term="%22Orton+AL%22">Orton AL</searchLink>; DMPK, Research and Early Development, Oncology R&D, AstraZeneca, Cambridge Science Park, Unit 310 Darwin Building, Cambridge CB4 0WG, United Kingdom.<br /><searchLink fieldCode="AU" term="%22Pearson+S%22">Pearson S</searchLink>; Medicinal Chemistry, Research and Early Development, Oncology R&D, AstraZeneca, Cambridge Science Park, Unit 310 Darwin Building, Cambridge CB4 0WG, United Kingdom.<br /><searchLink fieldCode="AU" term="%22Robb+GR%22">Robb GR</searchLink>; Medicinal Chemistry, Research and Early Development, Oncology R&D, AstraZeneca, Cambridge Science Park, Unit 310 Darwin Building, Cambridge CB4 0WG, United Kingdom.<br /><searchLink fieldCode="AU" term="%22Rosen+A%22">Rosen A</searchLink>; Bioscience, Research and Early Development, Oncology R&D, AstraZeneca, Boston, 35 Gatehouse Drive, Waltham, MA 02451, United States.<br /><searchLink fieldCode="AU" term="%22Scarfe+GB%22">Scarfe GB</searchLink>; DMPK, Research and Early Development, Oncology R&D, AstraZeneca, Cambridge Science Park, Unit 310 Darwin Building, Cambridge CB4 0WG, United Kingdom.<br /><searchLink fieldCode="AU" term="%22Scott+JS%22">Scott JS</searchLink>; Medicinal Chemistry, Research and Early Development, Oncology R&D, AstraZeneca, Cambridge Science Park, Unit 310 Darwin Building, Cambridge CB4 0WG, United Kingdom.<br /><searchLink fieldCode="AU" term="%22Smith+JM%22">Smith JM</searchLink>; Medicinal Chemistry, Research and Early Development, Oncology R&D, AstraZeneca, Cambridge Science Park, Unit 310 Darwin Building, Cambridge CB4 0WG, United Kingdom.<br /><searchLink fieldCode="AU" term="%22Steward+OR%22">Steward OR</searchLink>; Medicinal Chemistry, Research and Early Development, Oncology R&D, AstraZeneca, Cambridge Science Park, Unit 310 Darwin Building, Cambridge CB4 0WG, United Kingdom.<br /><searchLink fieldCode="AU" term="%22Terstiege+I%22">Terstiege I</searchLink>; Medicinal Chemistry, R&I, R&D, AstraZeneca, Gothenburg, SE-431 83 Mölndal, Sweden.<br /><searchLink fieldCode="AU" term="%22Tucker+MJ%22">Tucker MJ</searchLink>; Medicinal Chemistry, Research and Early Development, Oncology R&D, AstraZeneca, Cambridge Science Park, Unit 310 Darwin Building, Cambridge CB4 0WG, United Kingdom.<br /><searchLink fieldCode="AU" term="%22Turner+P%22">Turner P</searchLink>; Medicinal Chemistry, Research and Early Development, Oncology R&D, AstraZeneca, Cambridge Science Park, Unit 310 Darwin Building, Cambridge CB4 0WG, United Kingdom.<br /><searchLink fieldCode="AU" term="%22Wilkinson+SD%22">Wilkinson SD</searchLink>; DMPK, Research and Early Development, Oncology R&D, AstraZeneca, Cambridge Science Park, Unit 310 Darwin Building, Cambridge CB4 0WG, United Kingdom.<br /><searchLink fieldCode="AU" term="%22Wrigley+GL%22">Wrigley GL</searchLink>; Medicinal Chemistry, Research and Early Development, Oncology R&D, AstraZeneca, Cambridge Science Park, Unit 310 Darwin Building, Cambridge CB4 0WG, United Kingdom.<br /><searchLink fieldCode="AU" term="%22Xue+Y%22">Xue Y</searchLink>; Discovery Sciences, R&D, AstraZeneca, Gothenburg, SE-431 83 Mölndal, Sweden.
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