The target site of tolprocarb has been reported to be polyketide synthase (PKS). Here, we evaluated the activities for Pyricularia oryzae PKS and melanin biosynthesis as well as the control efficacy of rice blast using a series of tolprocarb derivatives. A comparison of the inhibitory activities of PKS and melanin biosynthesis revealed a linear relationship (r²=0.90), confirming PKS as the target site of tolprocarb. A compound beyond this relationship was metabolized by P. oryzae to an inactive compound. The control efficacy of rice blast was explained using the melting point and either the inhibitory activity of PKS or melanin biosynthesis. Structure–activity analysis revealed that both end parts of tolprocarb preferred hydrophobic groups, and the chirality of the substituent in the middle part significantly influenced the activities. These relationships will provide useful information for the development of novel PKS inhibitors.