pKa, Log P and MedChem CLOGP Fragment Values of Acidic Heterocyclic Potential Bioisosteres

Log P values have been measured for twenty phenyl and benzyl five membered heterocycles and alicyclic analogs that might function as acidic bioisosteres. pKa's have been measured by potentiometric titration in water and 1:1 dioxane‐water. From this experimental data, twelve missing fragmental CLOGP values are derived for use in calculating Log P values according to the Pomona College MedChem program. Log P values of some of the simple benzyl and phenyl heterocycles are compared to those measured for four clinically used drugs containing the same acidic moieties. Sulfonyl urea and acyl sulfonamide moieties have similar pKa and Log P values suggesting that these groups might be explored as bioisosteres.