Investigations of amination reactions on an antimalarial 1,2,4-triazolo[4,3-a]pyrazine scaffold

• Henry S. T. Smith,
• Ben Giuliani,
• Kanchana Wijesekera,
• Kah Yean Lum,
• Sandra Duffy,
• Aaron Lock,
• Jonathan M. White,
• Vicky M. Avery and
• Rohan A. Davis

Beilstein J. Org. Chem. 2025, 21, 1126–1134, doi:10.3762/bjoc.21.90

• School of Chemistry and Bio21 Institute, The University of Melbourne, Melbourne, VIC 3010, Australia, NatureBank, Griffith University, Brisbane, QLD 4111, Australia 10.3762/bjoc.21.90 Abstract 1,2,4-Triazolo[4,3-a]pyrazines have previously been explored by the Open Source Malaria project as potent in

• vitro and in vivo antimalarial drug leads. With a view to generating a library of unique antimalarial 1,2,4-triazolo[4,3-a]pyrazines and exploring regiochemical preference for nucleophilic amines, we utilised the known synthetic 5-chloro-3-(4-chlorophenyl)-[1,2,4]triazolo[4,3-a]pyrazine (1) as a

• substitution; antimalarial; open source malaria; triazolopyrazine; 1,2,4-triazolo[4,3-a]pyrazines; Introduction Malarial disease is a potentially fatal, acute febrile illness caused by infection with any of several species of vector-borne apicomplexan parasites in the genus Plasmodium [1]. The African endemic