Chlorocarbonylsulfenyl chloride cyclizations towards piperidin-3-yl-oxathiazol-2-ones as potential covalent inhibitors of threonine proteases
| Autor: | Marko Jukič, Stanislav Gobec, Aleš Obreza, Selmir Kadić, Izidor Sosič, Katarina Grabrijan, Fernando Juan de Lera Garrido |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
Threonine
Nitrile medicine.drug_class Carboxamide 010402 general chemistry 01 natural sciences Chloride lcsh:Chemistry chemistry.chemical_compound Piperidines medicine Organic chemistry Moiety Protease Inhibitors oxathiazole-2-one irreversible inhibition 010405 organic chemistry threonine protease 0104 chemical sciences Thiazoles lcsh:QD1-999 chemistry Cyclization amide dehydration Functional group Electrophile covalent inhibitors Piperidine Selectivity medicine.drug |
| Zdroj: | Acta chimica slovenica Acta Chimica Slovenica, Vol 64, Iss 4, Pp 771-781 (2017) |
| Popis: | 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. Z zamenjavo molekulskega skeleta smo načrtovali spojine s piperidinskim jedrom, derivatiziranim z oksatiazol-2-onskim elektrofilnim centrom, ki omogoča selektivno zaviranje treoninskih proteaz. Sinteza produktov po postopkih, opisanih v literaturi, ni bila uspešna, poleg tega smo identificirali nitrile kot glavne stranske produkte, ki nastanejo pri dehidraciji karboksamidne funkcionalne skupine. S sistematično optimizacijo reakcijskih pogojev, smo s segrevanjem karboksamidov, klorokarbonilsulfenil klorida in natrijevega karbonata kot baze v dioksanu pri 100 °C pripravili serijo piperidin-3-il-oksatiazol-2-onov, primerno za nadaljnje biološko vrednotenje. |
| Databáze: | OpenAIRE |
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