The invention relates to a propionamides compound and a usage thereof. The inventor, by carrying out SPR experiment based on Biacore and making comprehensive use of CADD, modifies the structure of a propionamide derivative and obtains an N-substituted-2-substituted amino-3-(1H-indole-3-yl) propionamides compound (the structure thereof is indicated by formula I). The falcipain-2 activity inhibiting capability of the obtained compound is tested, and the result shows that the prepared N-substituted-2-substituted amino-3-(1H-indole-3-yl) propionamides compound has strong falcipain-2 activity inhibiting capability and can be used for preparing medicaments for treating malaria caused by plasmodium.