Synthesis, Table of Contents Synthesis 2019; 51(18): 3491-3498DOI: 10.1055/s-0039-1689916 paper © Georg Thieme Verlag Stuttgart · New YorkA Facile Access to Novel (5+5) Annellated Heterocycles: Synthesis of a Furopyrrole, an Imidazoimidazole and a Pyrroloimidazole Authors Author Affiliations Pavol Zlatoidský∗ a Medicinal Chemistry, Respiratory, Inflammation And Autoimmunity, iMED Biotech. Unit, AstraZeneca, 43183 Gothenburg, Sweden Elisa Martinelli a Medicinal Chemistry, Respiratory, Inflammation And Autoimmunity, iMED Biotech. Unit, AstraZeneca, 43183 Gothenburg, Sweden Emil Svensson b Department of Chemistry and Molecular Biology, University of Gothenburg, 41296 Gothenburg, Sweden Alexis Pruvost c Faculte dé Pharmacie, Université de Lille, 59800 Lille, France Email: Pavol.Zlatoidsky@astrazeneca.com Recommend Article Abstract Buy Article(opens in new window) All articles of this category(opens in new window) Abstract We describe the synthesis of an ethyl 3-aryl-6H-furo[2,3-b]pyrrole-5-carboxylate 2, a 5-aryl-1H-imidazo[1,2-a]imidazole 3, and an ethyl-1-aryl-1,4-dihydropyrrolo[2,3-d]imidazole-5-carboxylate 4 as new hinge-binding motifs for PI3K kinase inhibitors. A key reaction for the formation of 2 and 4 is the Hemmetsberger–Knittel cyclization of acryloazides. The core of 3 is accessible through reaction of an α-haloketone with 2-aminoimidazole. Key words Key wordsHemmetsberger–Knittel cyclization - PI3K kinase inhibitors - adeninomimetics - (5+5) annellated heterocycles Full Text References References 1 Zhang J, Yang PL, Gray NS. Nat. Rev. Cancer 2009; 9: 28 ; and references cited therein 2 Cohen P. Nat. Cell Biol. 2002; 4: 127 3 Taylor SS, Kornev AP. Trends Biochem. Sci. 2011; 36: 65 ; and references cited therein 4 Wenglowsky S. Exp. Opin. Ther. Pat. 2013; 3: 281 5 Liu G, Abraham S, Liu X, Xu S, Rooks AM, Nepomuceno R, Dao A, Brigham D, Gitnick D, Insko DE. Bioorg. Med. Chem. Lett. 2015; 25: 3436 6 Abdelhafez OM, Ali HI, Amin KM, Abdalla MM, Ahmed EY. RSC Adv. 2015; 5: 25312 7 Belal A. Bioorg. Chem. 2015; 59: 124 8 Czodrowski P, Hoelzemann G, Barnickel G, Greiner H, Musil D. J. Med. Chem. 2015; 58: 457 9 Scior T, Domeyer DM, Cuanalo-Contreras K, Laufer SA. Curr. Med. Chem. 2011; 18: 1526 10 Darl AC, Shokat KM. Annu. Rev. Biochem. 2011; 80: 769 11 Zhao H, Caflisch A. Bioorg. Med. Chem. 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Soc., Perkin Trans. 1 1986; 1123 Supplementary Material Supplementary Material Supporting Information (PDF) (opens in new window)
