The active ingredient in Cinchona bark has been used for more than 3 centuries to treat malaria. The identification of the 2-hydroxy derivative, carbostyril, as a major urinary metabolite of cinchonine led to the synthesis of compounds designed to block the metabolic attack and thus increase effectiveness. A phenyl substituent at the 2-position increased antimalarial activity and many 2-phenyl-4-quinolinemethanols were synthesized and tested in vivo. Analogs of this type were originally abandoned in clinical trials as a result of a long-lasting phototoxic reaction. The phototoxicity associated with this type of analog may be related to the extended π-electron system involving the quinoline and phenyl substituent. This system results in a general delocalization of the electrons across all of the adjacent π-orbitals, which increases stability and thereby lowers the overall energy of the molecule. In order to disrupt the delocalization of the π-electrons, a methylene spacer was introduced between the quinoline and phenyl substituent. In addition, the increase in rotational freedom about the benzylic carbon inhibits the molecule from adopting a planar confirmation. The effect of such substitutions on antimalarial activity and phototoxicity will be reported.