Synthesis, biological activity and modelling studies of two novel anti HIV PR inhibitors with a thiophene containing hydroxyethylamino core

An efficient method has been developed for the synthesis of a versatile intermediate hearing azido, hydroxyl and ester functions, a useful precursor for peptidomimetic compounds. The two main features for this synthesis were the use of the Sharpless asymmetric dihydroxyiation on thiophene acrylate and the subsequent regioselective ring opening by sodium azide of the cyclic sulfite. Highly chemoselective reduction of the azido alcohol led to a key compound which was utilized for the synthesis of two analogues of commercial anti HIV PR such as nelfinavir and saquinavir. The biological activity and molecular modelling study on these two new potential drugs have been evaluated. (c) 2005 Elsevier Ltd. All rights reserved.