We studied the synthetic modification of structurally similar N-mercaptoacyl-l-proline and (4R)-N-mercaptoacylthiazolidine-4-carboxylic acid to obtain potent leukotriene A 4 (LTA 4 ) hydrolase inhibitors. An N-mercaptoacyl group, (2S)-3-mercapto-2-methylpropionyl group, was effective for both scaffolds. Additional introduction of a large substituent such as 4-isopropylbenzylthio (3f), 4-tert-butylbenzylthio (3l) or 4-cyclohexylbenzylthio group (3m) with (S)-configuration at the C 4 position of proline yielded much more potent LTA 4 hydrolase inhibitors (IC 50 ; 52, 31, and 34nM, respectively) than captopril (IC 50 ; 630,000nM).