Synthesis of a Potent Pan-Serotype Dengue Virus Inhibitor Having a Tetrahydrothienopyridine Core
| Autor: | Yugang Liu, Lei Zhang, Oliver Simon, Peichao Lu, Fumiaki Yokokawa, Kevin Hung, Christopher Sarko, Bryan K. S. Yeung |
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| Rok vydání: | 2020 |
| Předmět: |
0303 health sciences
Chemistry Organic Chemistry Regioselectivity Dengue virus Alkylation medicine.disease_cause Medicinal chemistry Acid anhydride Catalysis 03 medical and health sciences Acetic acid chemistry.chemical_compound 0302 clinical medicine 030220 oncology & carcinogenesis medicine Gewald reaction 030304 developmental biology Malononitrile |
| Zdroj: | Synlett. 33:464-467 |
| ISSN: | 1437-2096 0936-5214 |
| DOI: | 10.1055/a-1323-4036 |
| Popis: | A synthesis of the first-in-class pan-serotype dengue virus inhibitor NITD-688 is presented. The Gewald reaction of N-(tert-butoxycarbonyl)-6,6-dimethylpiperidin-3-one with malononitrile and sulfur in the presence of l-proline as a catalyst gave tert-butyl 2-amino-3-cyano-6,6-dimethyl-6,7-dihydrothieno[3,2-c]pyridine-5(4H)-carboxylate. This was coupled with [4-(aminosulfonyl)phenyl]acetic acid by using propanephosphonic acid anhydride. A subsequent reductive alkylation with cyclohexanecarboxaldehyde gave NITD-688. Preliminary results of our attempts to control the regioselectivity of the Gewald synthesis of the 2-amino-3-cyanothiophene core are also presented. |
| Databáze: | OpenAIRE |
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