A series of HIV-1 protease inhibitors having new THF P2/P2' groups have been synthesized and tested for protease inhibition and antiviral activity. Six novel 4-aminotetrahydrofuran derivs. were prepd. starting from com. available isopropylidene-a-D-xylofuranose yielding six sym. and six unsym. inhibitors. Promising sub nanomolar HIV-1 protease inhibitory activities were obtained. The x-ray crystal structure of the most potent inhibitor (23, Ki 0.25 nM) co-crystd. with HIV-1 protease is discussed and the binding compared with inhibitors 1a and 1b. [on SciFinder (R)]