Identification of a Potential Antimalarial Drug Candidate from a Series of 2-Aminopyrazines by Optimization of Aqueous Solubility and Potency across the Parasite Life Cycle.
J Med Chem
; 59(21): 9890-9905, 2016 11 10.
Article
in En
| MEDLINE
| ID: mdl-27748596
ABSTRACT
Introduction of water-solubilizing groups on the 5-phenyl ring of a 2-aminopyrazine series led to the identification of highly potent compounds against the blood life-cycle stage of the human malaria parasite Plasmodium falciparum. Several compounds displayed high in vivo efficacy in two different mouse models for malaria, P. berghei-infected mice and P. falciparum-infected NOD-scid IL-2Rγnull mice. One of the frontrunners, compound 3, was identified to also have good pharmacokinetics and additionally very potent activity against the liver and gametocyte parasite life-cycle stages.
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Collection:
01-internacional
Database:
MEDLINE
Main subject:
Parasitic Diseases, Animal
/
Plasmodium berghei
/
Plasmodium falciparum
/
Pyrazines
/
Life Cycle Stages
/
Malaria
/
Antimalarials
Type of study:
Diagnostic_studies
/
Prognostic_studies
Limits:
Animals
/
Humans
Language:
En
Journal:
J Med Chem
Journal subject:
QUIMICA
Year:
2016
Document type:
Article
Affiliation country:
Sudáfrica