Details

Autor(en) / Beteiligte

• Lowes, David J.
• Guiguemde, W. Armand
• Connelly, Michele C.
• Zhu, Fangyi
• Sigal, Martina S.
• Clark, Julie A.
• Lemoff, Andrew S.
• Derisi, Joseph L.
• Wilson, Emily B.
• Guy, R. Kiplin

Titel

Optimization of Propafenone Analogues as Anti-Malarial Leads

Ist Teil von

• Journal of medicinal chemistry, 2011-10, Vol.54 (21), p.7477-7485

Erscheinungsjahr

2011

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• Propafenone, a class Ic antiarrythmic drug, inhibits growth of cultured Plasmodium falciparum . While the drug’s potency is significant, further development of propafenone as an antimalarial would require divorcing the antimalarial and cardiac activities as well as improving the pharmacokinetic profile of the drug. A small array of propafenone analogs was designed and synthesized to address the cardiac ion channel and PK liabilities. Testing of this array revealed potent inhibitors of the 3D7 (drug sensitive) and K1 (drug resistant) strains of P. falciparum that possessed significantly reduced ion channel effects and improved metabolic stability. Propafenone analogues are unusual among antimalarial leads in that they are more potent against the multi-drug resistant K1 strain of P. falciparum compared to the 3D7 strain.