Chlorocarbonylsulfenyl chloride cyclizations towards piperidin-3-yl-oxathiazol-2-ones as potential covalent inhibitors of threonine proteases
Using rescaffolding approach, we designed piperidine compounds decorated with an electrophilic oxathiazol-2-one moiety that is known to confer selectivity towards threonine proteases. Our efforts to prepare products according to the published procedures were not successful. Furthermore we identified...
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Slovenian Chemical Society
2017-12-01
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Online Access: | https://journals.matheo.si/index.php/ACSi/article/view/3883 |
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doaj-8d35d2c7795842f1ad7bb5a288d7f70e2020-11-25T02:53:17ZengSlovenian Chemical SocietyActa Chimica Slovenica1318-02071580-31552017-12-0164477178110.17344/acsi.2017.3883535Chlorocarbonylsulfenyl chloride cyclizations towards piperidin-3-yl-oxathiazol-2-ones as potential covalent inhibitors of threonine proteasesAles Obreza0Katarina GrabrijanSelmir KadićFernando Juan de Lera GarridoIzidor SosičStanislav GobecMarko JukičUniversity of Ljubljana, Faculty of Pharmacy, Department of medicinal chemistry; Aškerčeva 7, SI-1000, Ljubljana, SloveniaUsing rescaffolding approach, we designed piperidine compounds decorated with an electrophilic oxathiazol-2-one moiety that is known to confer selectivity towards threonine proteases. Our efforts to prepare products according to the published procedures were not successful. Furthermore we identified major side products containing nitrile functional group, resulting from carboxamide dehydration. We systematically optimized reaction conditions towards our desired products to identify heating of carboxamides with chlorocarbonylsulfenyl chloride and sodium carbonate as base in dioxane at 100 °C. Our efforts culminated in the preparation of a small series of piperidin-3-yl-oxathiazol-2-ones that are suitable for further biological evaluation.https://journals.matheo.si/index.php/ACSi/article/view/3883cyclizationamide dehydrationoxathiazole-2-onethreonine proteasecovalent inhibitorsirreversible inhibition |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Ales Obreza Katarina Grabrijan Selmir Kadić Fernando Juan de Lera Garrido Izidor Sosič Stanislav Gobec Marko Jukič |
spellingShingle |
Ales Obreza Katarina Grabrijan Selmir Kadić Fernando Juan de Lera Garrido Izidor Sosič Stanislav Gobec Marko Jukič Chlorocarbonylsulfenyl chloride cyclizations towards piperidin-3-yl-oxathiazol-2-ones as potential covalent inhibitors of threonine proteases Acta Chimica Slovenica cyclization amide dehydration oxathiazole-2-one threonine protease covalent inhibitors irreversible inhibition |
author_facet |
Ales Obreza Katarina Grabrijan Selmir Kadić Fernando Juan de Lera Garrido Izidor Sosič Stanislav Gobec Marko Jukič |
author_sort |
Ales Obreza |
title |
Chlorocarbonylsulfenyl chloride cyclizations towards piperidin-3-yl-oxathiazol-2-ones as potential covalent inhibitors of threonine proteases |
title_short |
Chlorocarbonylsulfenyl chloride cyclizations towards piperidin-3-yl-oxathiazol-2-ones as potential covalent inhibitors of threonine proteases |
title_full |
Chlorocarbonylsulfenyl chloride cyclizations towards piperidin-3-yl-oxathiazol-2-ones as potential covalent inhibitors of threonine proteases |
title_fullStr |
Chlorocarbonylsulfenyl chloride cyclizations towards piperidin-3-yl-oxathiazol-2-ones as potential covalent inhibitors of threonine proteases |
title_full_unstemmed |
Chlorocarbonylsulfenyl chloride cyclizations towards piperidin-3-yl-oxathiazol-2-ones as potential covalent inhibitors of threonine proteases |
title_sort |
chlorocarbonylsulfenyl chloride cyclizations towards piperidin-3-yl-oxathiazol-2-ones as potential covalent inhibitors of threonine proteases |
publisher |
Slovenian Chemical Society |
series |
Acta Chimica Slovenica |
issn |
1318-0207 1580-3155 |
publishDate |
2017-12-01 |
description |
Using rescaffolding approach, we designed piperidine compounds decorated with an electrophilic oxathiazol-2-one moiety that is known to confer selectivity towards threonine proteases. Our efforts to prepare products according to the published procedures were not successful. Furthermore we identified major side products containing nitrile functional group, resulting from carboxamide dehydration. We systematically optimized reaction conditions towards our desired products to identify heating of carboxamides with chlorocarbonylsulfenyl chloride and sodium carbonate as base in dioxane at 100 °C. Our efforts culminated in the preparation of a small series of piperidin-3-yl-oxathiazol-2-ones that are suitable for further biological evaluation. |
topic |
cyclization amide dehydration oxathiazole-2-one threonine protease covalent inhibitors irreversible inhibition |
url |
https://journals.matheo.si/index.php/ACSi/article/view/3883 |
work_keys_str_mv |
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