pH-partition profiles of 4-(3-oxo-1,2-benzisothiazolin-2-yl)phenyl and phenoxyalkanoic acids

Farmaco. 2003 Sep;58(9):989-93. doi: 10.1016/S0014-827X(03)00156-3.

Abstract

The 1,2-benzisothiazolin-3-one nucleus is well known in the medicinal chemistry literature for the variety of biological effects exerted by its derivatives. In the present paper, the dependence of the n-octanol/buffer distribution coefficient (D) on pH of four 4-(3-oxo-1,2-benzisothiazolin-2-yl)phenyl and phenoxyalkanoic acids was investigated, employing the reference shake-flask method. From the analysis of the pH-partition profiles in the chosen partition system, the logP(AH), the logP(A(-)) and the pK(a) values for each compound were determined. The physico-chemical data obtained were compared to the pK(a) and logP values of the corresponding phenyl and phenoxyalkanoic acids, and an estimation of the lipophilic and electronic contribution of the 1,2-benzisothiazolin-3-one substituent in the para-position is proposed. The 1,2-benzisothiazolin-3-one nucleus behaves as a lipophilic, moderately electron-withdrawing group.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 1-Octanol
  • Buffers
  • Chemistry, Pharmaceutical
  • Hydrogen-Ion Concentration
  • Hydroxy Acids / chemistry*
  • Thiazoles / chemistry*

Substances

  • Buffers
  • Hydroxy Acids
  • Thiazoles
  • benzisothiazole
  • 1-Octanol