Relationships between Hydrophobicity and Algistatic Activity of 5‐Aryl‐3H‐[1,3,4]oxadiazole‐2‐thiones

A series of 10 acidic 5-aryl-3H-[1,3,4]oxadiazole-2-thiones was synthesized and characterized with regard to hydrophobic and algistatic properties. Apparent octan-1-ol/water (buffer pH=7.41) partition coefficients (logPapp) were determined by the shake-flask method and used to calculate the partition coefficients of the un-ionized molecules (logPu) on the basis of known pKa values. Relationships between both sets of logP and hydrophobic substituent constants are reported. Biological activity parameters (logA) were derived from growth tests using autotrophic Chlorella vulgaris cultures. The obtained data sets of logA and logP were used in QSAR studies. In this way it could be shown that the algistatic activity of meta- and para-substituted 5-aryl-3H-[1,3,4]-oxadiazole-2-thiones strongly correlates with logPapp, but slightly poorer with logPu. The results are discussed and compared with analogous QSAR/QSPR found for earlier studied series of five-membered N-heterocycles (2-amino-5-aryl-[1,3,4]oxadiazoles, 4-aryl-5-alkyl-2,4-dihydro-[1,2,4]triazol-3-ones, 5-amino-1-aryl-1H-tetrazoles).