Figure 1.

2,3-Substituted benzo[b]thiophene PfNMT and PvNMT inhibitor 1 and the target profile for the development of this series. Footnote a: K_i values are quoted in place of IC₅₀ values as a means of expressing the inhibitor affinity while correcting for differing Michaelis constants (K_m) between enzymes. Enzyme K_i values are calculated from the IC₅₀ values using the Cheng–Prusoff equation, the definition of which is given in the Experimental Section.²³ IC₅₀ values are the mean value of two or more determinations, and standard deviation is within 20% of the IC₅₀. Footnote b: No significant difference in inhibition between HsNMT1 and HsNMT2 isoforms has been observed in this series; therefore, the HsNMT affinities reported in this work refer to HsNMT1. Footnote c: LELP = cLogP/LE. LE = [−log(K_i)](1.374)/(no. of heavy atoms), with cLogP determined with ChemAxon, which can be obtained from http://www.chemaxon.com/products/calculator-plugins/logp/.