53498-75-2Relevant academic research and scientific papers
Enantiopure substituted pyridines as promising antimalarial drug candidates
Agnamey, Patrice,Bentzinger, Guillaume,Dassonville-Klimpt, Alexandra,Guillon, Jean,Marchivie, Mathieu,Pair, Etienne,Sonnet, Pascal,Mullié, Catherine
, (2020)
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 Kr?hnke-type cyclization or on metal-catalyzed reactions. The Kr?hnke-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.
2-Substituted phenyl-6-trifluoromethyl-4-pyridyl-carbinolamines
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, (2008/06/13)
A series of 2-aryl-6-trifluoromethyl-4-pyridylcarbinolamines is herein disclosed which has value in treatment of plasmodial infections. The compounds have substituted phenyl groups at position 2- on the pyridine moiety, with the electronegative substituents present on the phenyl nuclei. The syntheses of such series is described, together with a method for separation of racemates of a representative 4-pyridylcarbinolamine type.
