Analogues of phenylalanine and lysine esters were synthesized, and their inhibitory power tested in vitro respectively on chyrnonypsin, trypsin and uroklnase. Electrophilic phosphonate analogues of N-acylated amino acids (e. g. structures 4 and 12) are potent inhibitors of serine proteasesl. These enzymes are involved in a number of important physiological processes. Their detuning creates a pathological state implying local degradation of the extracellular matrix and breaking of intercellular bridges. Especially, the uroldnase type plasminogen activator (uPA) seems to play a key role in inflammatory reactions, ovulation, fertilization, and embryogenesis . Increased uPA activities have been reported in different diseases including pulmonary fibrosis, arthritis, dermatitis and neoplasia2. According to its subsnate specificity, uPA should be selectively inhibited by the phosphonate mimics of N-acylated lysine or arginine active esters. This paper describes the preparation of these original compounds. To get the phosphonate analogues of lysine 12b-c, we first optimized a relevant strategy by synthesizing the phenylalanine mimics 4c-d. Jn vitro, 4cd inhibit chymotrypsin, and 12b-c txypsin and (less efficiently) urokinase.