AM1 theoretical study, synthesis and biological evaluation of some benzofuran analogues of anti-inflammatory arylalkanoic acids

Using the semi-empirical quantum-mechanical method AM1, the molecular geome tries of the arylalkanoic acids, indomethacin, naproxen and ibuprofen, were optimized and their frontier orbital charge distributions evaluated. Then, these molecular parameters were compared in order to identify structure-ac tivity relationships and, on the basis of these, four benzofuran-3-acetic a cids were designed as potential non-steroidal anti-inflammatory agents, and rapidly synthesized by a novel and easily generalized route. Notwithstandi ng the structural similarities between the synthesized compounds and the an ti-inflammatory arylalkanoic acids, these compounds did not appreciably inh ibit human platelet cyclooxygenase in vitro. (C) 1998 Elsevier Science B.V. All rights reserved.