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Enantiopure substituted pyridines as promising antimalarial drug candidates

hal.structure.identifierAgents infectieux, résistance et chimiothérapie - UR UPJV 4294 [AGIR ]
dc.contributor.authorBENTZINGER, Guillaume
hal.structure.identifierAgents infectieux, résistance et chimiothérapie - UR UPJV 4294 [AGIR ]
dc.contributor.authorPAIR, Etienne
hal.structure.identifierAcides Nucléiques : Régulations Naturelle et Artificielle [ARNA]
dc.contributor.authorGUILLON, Jean
hal.structure.identifierInstitut de Chimie de la Matière Condensée de Bordeaux [ICMCB]
dc.contributor.authorMARCHIVIE, Mathieu
hal.structure.identifierAgents infectieux, résistance et chimiothérapie - UR UPJV 4294 [AGIR ]
dc.contributor.authorMULLIÉ, Catherine
hal.structure.identifierAgents infectieux, résistance et chimiothérapie - UR UPJV 4294 [AGIR ]
dc.contributor.authorAGNAMEY, Patrice
hal.structure.identifierAgents infectieux, résistance et chimiothérapie - UR UPJV 4294 [AGIR ]
dc.contributor.authorDASSONVILLE-KLIMPT, Alexandra
hal.structure.identifierAgents infectieux, résistance et chimiothérapie - UR UPJV 4294 [AGIR ]
dc.contributor.authorSONNET, Pascal
dc.date.issued2020-04
dc.identifier.issn0040-4020
dc.description.abstractEnWe describe the enantioselective synthesis and biological evaluation of 4-(2-amino-1-hydroxyethyl)pyridines (4 AHPs) as new antimalarial drug candidates. In particular, two routes to obtain the key-intermediate 4-vinyl-pyridine were studied. These routes are based on a Kröhnke-type cyclization or on metal-catalyzed reactions. The Kröhnke-type cyclization route is faster but only efficient at low scale since this pathway involves a Wittig reaction that requires severe temperature-control. Consequently, we designed a second route based on metal-catalyzed reactions. This way is longer but the 4-vinyl-pyridine can be obtained on a 5 g scale at least. Finally, a regioselective SN2 ring-opening of enantiopure epoxides by alkyl primary amines allowed the synthesis of eight 4-AHPs with global yields up to 41%. These compounds show strong in vitro antimalarial activity against P. falciparum strains and are more active that chloroquine and mefloquine. These results demonstrate that 4-AHPs are promising antimalarial drug candidates.
dc.language.isoen
dc.publisherElsevier
dc.rights.urihttp://creativecommons.org/licenses/by-nc/
dc.subject.enMalaria P. falciparum
dc.subject.enArylaminoalcohols
dc.subject.enEnpiroline
dc.subject.enAsymmetric synthesis
dc.title.enEnantiopure substituted pyridines as promising antimalarial drug candidates
dc.typeArticle de revue
dc.identifier.doi10.1016/j.tet.2020.131088
dc.subject.halChimie/Matériaux
dc.subject.halSciences du Vivant [q-bio]
bordeaux.journalTetrahedron
bordeaux.page131088 (10 p.)
bordeaux.volume76
bordeaux.issue15
bordeaux.peerReviewedoui
hal.identifierhal-03611926
hal.version1
hal.popularnon
hal.audienceInternationale
hal.origin.linkhttps://hal.archives-ouvertes.fr//hal-03611926v1
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