Synthesis and biological evaluation of N-mercaptoacylproline and N-mercaptoacylthiazolidine-4-carboxylic acid derivatives as leukotriene A4 hydrolase inhibitors.

Abstract We studied the synthetic modification of structurally similar N -mercaptoacyl- l -proline and (4 R )- N -mercaptoacylthiazolidine-4-carboxylic acid to obtain potent leukotriene A 4 (LTA 4 ) hydrolase inhibitors. An N -mercaptoacyl group, (2 S )-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 34 nM, respectively) than captopril (IC 50 ; 630,000 nM).