Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
2487724 | Journal of Pharmaceutical Sciences | 2007 | 12 Pages |
Abstract
The ironâmediated reactivity of various dispiroâ1,2,4âtrioxolanes was determined by automated kinetic analysis under standard reaction conditions. The active antimalarial compounds underwent peroxide bond cleavage by Fe(II) resulting in products indicative of carbonâcentered radical formation. The rate of reaction was heavily influenced by the presence of spiroâsubstituted adamantane and cyclohexane rings, and was also significantly affected by cyclohexane ring substitution. Steric hindrance around the peroxide oxygen atoms appeared to be the major determinant of reaction rate, however polar substituents also affected reactivity by an independent mechanism. A wide range of reaction rates was observed within this class of peroxide antimalarials, however ironâmediated reactivity did not directly correlate with in vitro antimalarial activity. © 2007 WileyâLiss, Inc. and the American Pharmacists Association J Pharm Sci 96: 2945-2956, 2007
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Authors
Darren J. Creek, William N. Charman, Francis C.K. Chiu, Richard J. Prankerd, Kevin J. McCullough, Yuxiang Dong, Jonathan L. Vennerstrom, Susan A. Charman,