TY - JOUR
T1 - Discovery of novel and potent benzhydryl-tropane trypanocides highly selective for Trypanosoma cruzi
AU - Holloway, Georgina A
AU - Parisot, John P
AU - Novello, Patrizia M
AU - Watson, Keith Geoffrey
AU - Armstrong, Tanya
AU - Thompson, Richard Christopher Andrew
AU - Street, Ian Philip
AU - Baell, Jonathan Bayldon
PY - 2010
Y1 - 2010
N2 - A benzhydryl tropinone oxime that is potently toxic to Trypanosoma cruzi has been previously identified. An SAR investigation determined that no part of the original compound was superfluous and all early SAR probes led to significant drops in activity. The only alteration that could be achieved without loss of activity was replacement of the aryl chloride substituent with chloro homologues. This led to the discovery of a trifluoromethyl-containing analogue with an EC50 against T. cruzi of 30 nM and a cytotoxicity selectivity index of over 1000 relative to rat skeletal myoblast L-6 cells
AB - A benzhydryl tropinone oxime that is potently toxic to Trypanosoma cruzi has been previously identified. An SAR investigation determined that no part of the original compound was superfluous and all early SAR probes led to significant drops in activity. The only alteration that could be achieved without loss of activity was replacement of the aryl chloride substituent with chloro homologues. This led to the discovery of a trifluoromethyl-containing analogue with an EC50 against T. cruzi of 30 nM and a cytotoxicity selectivity index of over 1000 relative to rat skeletal myoblast L-6 cells
UR - http://www.sciencedirect.com/science/article/pii/S0960894X1000212X
U2 - 10.1016/j.bmcl.2010.02.022
DO - 10.1016/j.bmcl.2010.02.022
M3 - Article
SN - 0960-894X
VL - 20
SP - 1816
EP - 1818
JO - Bioorganic and Medicinal Chemistry Letters
JF - Bioorganic and Medicinal Chemistry Letters
IS - 6
ER -