Bioassay-guided separation use of the fission yeast expressing NES of Rev, a HIV-1 viral regulatory protein, resulted in isolation of 1'-acetoxychavicol acetate (ACA) from Alpinia galanga as a new Rev-transport inhibitor from the nucleus to cytoplasm. Rational design and synthesis of eleven ACA derivatives containing systematic chemical variations were made, biological evaluation of inhibitory activities of these analogues provides the basis to formulate the structure-activity relationship (SAR). The key elements observed were: (1) The para substitution of the acetoxyl and 1'-acetoxypropenyl groups at the benzene ring was essential, (2) linear ethyl and propyl chain carbonates were more active than branching chain carbonates, (3) the substitution of acetoxyl groups with alkyl carbamate groups lost or reduced the activities. This study revealed a new salient pharmacophore features as potential drug leads against the HIV virus.