Enantiopure substituted pyridines as promising antimalarial drug candidates
hal.structure.identifier | Agents infectieux, résistance et chimiothérapie - UR UPJV 4294 [AGIR ] | |
dc.contributor.author | BENTZINGER, Guillaume | |
hal.structure.identifier | Agents infectieux, résistance et chimiothérapie - UR UPJV 4294 [AGIR ] | |
dc.contributor.author | PAIR, Etienne | |
hal.structure.identifier | Acides Nucléiques : Régulations Naturelle et Artificielle [ARNA] | |
dc.contributor.author | GUILLON, Jean | |
hal.structure.identifier | Institut de Chimie de la Matière Condensée de Bordeaux [ICMCB] | |
dc.contributor.author | MARCHIVIE, Mathieu | |
hal.structure.identifier | Agents infectieux, résistance et chimiothérapie - UR UPJV 4294 [AGIR ] | |
dc.contributor.author | MULLIÉ, Catherine | |
hal.structure.identifier | Agents infectieux, résistance et chimiothérapie - UR UPJV 4294 [AGIR ] | |
dc.contributor.author | AGNAMEY, Patrice | |
hal.structure.identifier | Agents infectieux, résistance et chimiothérapie - UR UPJV 4294 [AGIR ] | |
dc.contributor.author | DASSONVILLE-KLIMPT, Alexandra | |
hal.structure.identifier | Agents infectieux, résistance et chimiothérapie - UR UPJV 4294 [AGIR ] | |
dc.contributor.author | SONNET, Pascal | |
dc.date.issued | 2020-04 | |
dc.identifier.issn | 0040-4020 | |
dc.description.abstractEn | We 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.iso | en | |
dc.publisher | Elsevier | |
dc.rights.uri | http://creativecommons.org/licenses/by-nc/ | |
dc.subject.en | Malaria P. falciparum | |
dc.subject.en | Arylaminoalcohols | |
dc.subject.en | Enpiroline | |
dc.subject.en | Asymmetric synthesis | |
dc.title.en | Enantiopure substituted pyridines as promising antimalarial drug candidates | |
dc.type | Article de revue | |
dc.identifier.doi | 10.1016/j.tet.2020.131088 | |
dc.subject.hal | Chimie/Matériaux | |
dc.subject.hal | Sciences du Vivant [q-bio] | |
bordeaux.journal | Tetrahedron | |
bordeaux.page | 131088 (10 p.) | |
bordeaux.volume | 76 | |
bordeaux.issue | 15 | |
bordeaux.peerReviewed | oui | |
hal.identifier | hal-03611926 | |
hal.version | 1 | |
hal.popular | non | |
hal.audience | Internationale | |
hal.origin.link | https://hal.archives-ouvertes.fr//hal-03611926v1 | |
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