Optimization of propafenone analogues as antimalarial leads.
Optimization of propafenone analogues as antimalarial leads.
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DOI：
10.1021/jm2005546
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发表时间：
2011-11-10
影响因子：
7.3
通讯作者：
Guy, R. Kiplin
中科院分区：
文献类型：
--
作者：
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
丙帕酮是一类抗心律失常药物，可抑制培养的恶性疟原虫的生长。虽然这种药物的效力很显著，但进一步开发普罗帕酮作为抗疟疾药物将需要分离抗疟疾和心脏活动，并改善药物的药代动力学特征。设计并合成了一个小阵列的普罗帕酮类似物，以解决心脏离子通道和PK责任。对该阵列的测试显示，恶性疟原虫3D7（药敏）和K1（耐药）菌株的有效抑制剂显著降低了离子通道效应，提高了代谢稳定性。普罗帕酮类似物在抗疟疾先导物中是不寻常的，因为它们对多重耐药的恶性疟原虫K1菌株比3D7菌株更有效。
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.
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影响因子：
--
作者：
Madrid, PB;Wilson, NT;Guy, RK
通讯作者：
Guy, RK
影响因子：
3.6
作者：
Reder-Hilz, B;Ullrich, M;Hengstler, JG
通讯作者：
Hengstler, JG
DOI：
10.1124/jpet.103.052993
发表时间：
2003-11-01
影响因子：
3.5
作者：
Schmid, D;Staudacher, DL;Chiba, P
通讯作者：
Chiba, P
影响因子：
11.8
作者：
Olliaro, P
通讯作者：
Olliaro, P
影响因子：
1.8
作者：
Lindström, UM;Olofsson, B;Somfai, P
通讯作者：
Somfai, P