Synthesis and Structure–Activity Relationships of 4-Pyridones as Potential Antimalarials Export

@article{Yeates09, abstract = {A series of diaryl ether substituted 4-pyridones have been identified as having potent antimalarial activity superior to that of chloroquine against Plasmodium falciparum in vitro and murine Plasmodium yoelii in vivo. These were derived from the anticoccidial drug clopidol through a systematic study of the effects of varying the side chain on activity. Relative to clopidol the most active compounds show >500-fold improvement in IC50 for inhibition of P. falciparum in vitro and about 100-fold improvement with respect to ED50 against P. yoelii in mice. These compounds have been shown elsewhere to act selectively by inhibition of mitochondrial electron transport at the cytochrome bc1 complex.}, author = {Yeates, Clive L. and Batchelor, John F. and Capon, Edward C. and Cheesman, Neil J. and Fry, Mitch and Hudson, Alan T. and Pudney, Mary and Trimming, Helen and Woolven, James and Bueno, Jos\'{e} M. and Chicharro, Jes\'{u}s and Fern\'{a}ndez, Esther and Fiandor, Jos\'{e} M. and Gargallo-Viola, Domingo and G\'{o}mez and Herreros, Esperanza and Le\'{o}n, Mar\'{\i}a L.}, citeulike-article-id = {4324844}, citeulike-linkout-0 = {http://dx.doi.org/10.1021/jm0705760}, citeulike-linkout-1 = {http://pubs.acs.org/doi/abs/10.1021/jm0705760}, day = {1}, doi = {10.1021/jm0705760}, journal = {Journal of Medicinal Chemistry}, keywords = {4-pyridones, anticoccidial, clopidol, drug, electron, malaria, mitochondrial, transport}, month = {May}, number = {9}, pages = {2845--2852}, posted-at = {2009-04-16 07:57:00}, priority = {2}, title = {Synthesis and Structure–Activity Relationships of 4-Pyridones as Potential Antimalarials}, url = {http://dx.doi.org/10.1021/jm0705760}, volume = {51}, year = {2008} }

TY - JOUR ID - Yeates09 L3 - citeulike-article-id:4324844 N2 - A series of diaryl ether substituted 4-pyridones have been identified as having potent antimalarial activity superior to that of chloroquine against Plasmodium falciparum in vitro and murine Plasmodium yoelii in vivo. These were derived from the anticoccidial drug clopidol through a systematic study of the effects of varying the side chain on activity. Relative to clopidol the most active compounds show >500-fold improvement in IC50 for inhibition of P. falciparum in vitro and about 100-fold improvement with respect to ED50 against P. yoelii in mice. These compounds have been shown elsewhere to act selectively by inhibition of mitochondrial electron transport at the cytochrome bc1 complex. IS - 9 JF - Journal of Medicinal Chemistry EP - 2852 TI - Synthesis and Structure–Activity Relationships of 4-Pyridones as Potential Antimalarials VL - 51 SP - 2845 KW - 4-pyridones KW - anticoccidial KW - clopidol KW - drug KW - electron KW - malaria KW - mitochondrial KW - transport AU - Yeates, Clive AU - Batchelor, John AU - Capon, Edward AU - Cheesman, Neil AU - Fry, Mitch AU - Hudson, Alan AU - Pudney, Mary AU - Trimming, Helen AU - Woolven, James AU - Bueno, José AU - Chicharro, Jesús AU - Fernández, Esther AU - Fiandor, José AU - Gargallo-Viola, Domingo AU - Gómez AU - Herreros, Esperanza AU - León, María PY - 2008/05/01/ UR - http://dx.doi.org/10.1021/jm0705760 ER -