3‑((Hetera)cyclobutyl)azetidines, “Stretched” Analogues of Piperidine, Piperazine, and Morpholine: Advanced Building Blocks for Drug Discovery

Four 3-((hetera)­cyclobutyl)­azetidine-based isosteres of piperidine, piperazine, and morpholine were designed and synthesized on up to gram scale. The key step of the synthetic sequence included cyclization of N-protected 2-(azetidin-3-yl)­propane-1,3-diol or the corresponding 1,3-dibromide. X-ray...

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Published in:Journal of organic chemistry 2019-02, Vol.84 (3), p.1363-1371
Main Authors: Feskov, Illia O, Chernykh, Anton V, Kuchkovska, Yuliya O, Daniliuc, Constantin G, Kondratov, Ivan S, Grygorenko, Oleksandr O
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cited_by cdi_FETCH-LOGICAL-a333t-656d4f51b65f1dae53613d2c6ba2dc8aebf6ec61b3aa6bf66f6e82e05c14ebaf3
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container_title Journal of organic chemistry
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creator Feskov, Illia O
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description Four 3-((hetera)­cyclobutyl)­azetidine-based isosteres of piperidine, piperazine, and morpholine were designed and synthesized on up to gram scale. The key step of the synthetic sequence included cyclization of N-protected 2-(azetidin-3-yl)­propane-1,3-diol or the corresponding 1,3-dibromide. X-ray diffraction studies of the products obtained, followed by exit vector plot analysis of their molecular geometry, demonstrated their larger size and increased conformational flexibility as compared to the parent heterocycles and confirmed their potential utility as building blocks for lead optimization programs.
doi_str_mv 10.1021/acs.joc.8b02822
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title 3‑((Hetera)cyclobutyl)azetidines, “Stretched” Analogues of Piperidine, Piperazine, and Morpholine: Advanced Building Blocks for Drug Discovery
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