QUANTUM-MECHANICAL AND QSAR STUDY OF SOME ALPHA-ARYLPROPIONIC ACIDS AS ANTIINFLAMMATORY AGENTS

The optimal structures of a series of alpha-arylpropionic acids with a nti-inflammatory activity are established by using the semi-empirical quantum mechanical procedures, AM1 and AMSOL, in the gas phase and in water solution, respectively. In these calculations, the arylpropionic acids are considered in their neutral and ionized forms. As expected, these compounds exhibit two preferred conformations in which the alph a-hydrogen atoms of the propionic acid group lies approximately in the plane of the central aryl ring. The deprotonation energies are then d etermined as the difference between the formation energies of the prot onated and deprotonated forms. A Quantitative Structure Activity Relat ionship (QSAR) study reveals that only the gas phase results compare t o some extent favorably with the anti-inflammatory activity. As expect ed, the smaller the deprotonation energy, the larger the anti-inflamma tory activity. Satisfactory relationships between the in vivo activiti es and deprotonation energies, the HOMO energies and lipophilicities w ere found. (C) Elsevier, Paris.