Discovery of a Bulky 2-tert-Butyl Group Containing Primaquine Analogue That Exhibits Potent Blood-Schizontocidal Antimalarial Activities and Complete Elimination of Methemoglobin Toxicity

To eliminate an unwarranted metabolic pathway of the quinoline ring, a set of two compounds, where C-2 position of the antimalarial drug primaquine is blocked by metabolically stable bulky alkyl group are synthesized. Compound 2 [R = C(CH3)3] of the series has produced excellent antimalarial efficac...

Full description

Saved in:
Bibliographic Details
Published in:Journal of medicinal chemistry 2004-01, Vol.47 (2), p.285-287
Main Authors: Jain, Meenakshi, Vangapandu, Suryanarayana, Sachdeva, Sandeep, Singh, Savita, Singh, Prati P, Jena, Gopa B, Tikoo, Kulbhushan, Ramarao, Poduri, Kaul, Chaman L, Jain, Rahul
Format: Article
Language:English
Subjects:
Animals
Antibiotics. Antiinfectious agents. Antiparasitic agents
Antimalarials - chemical synthesis
Antimalarials - pharmacology
Antimalarials - toxicity
Antiparasitic agents
Biological and medical sciences
Malaria - blood
Malaria - mortality
Malaria - parasitology
Medical sciences
Methemoglobin - analysis
Mice
Pharmacology. Drug treatments
Plasmodium berghei - drug effects
Plasmodium falciparum - drug effects
Plasmodium yoelii - drug effects
Primaquine - analogs & derivatives
Primaquine - chemical synthesis
Primaquine - pharmacology
Primaquine - toxicity
Structure-Activity Relationship
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:To eliminate an unwarranted metabolic pathway of the quinoline ring, a set of two compounds, where C-2 position of the antimalarial drug primaquine is blocked by metabolically stable bulky alkyl group are synthesized. Compound 2 [R = C(CH3)3] of the series has produced excellent antimalarial efficacy against P. berghei and highly virulent multidrug-resistant P. yoelii nigeriensis strain in vivo. Compound 2 was also evaluated for methemoglobin (MetHb) toxicity. This study describes the discovery of a highly potent blood-schizontocidal antimalarial analogue 2, completely devoid of MetHb toxicity.
ISSN:0022-2623
1520-4804
DOI:10.1021/jm0304562