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

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Enomoto H, Morikawa Y, Miyake Y, Tsuji F, Mizuchi M, Suhara H, Fujimura K, Horiuchi M, Ban M

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

Bioorg Med Chem Lett. 2008 Aug 15;18(16):4529-32. doi: 10.1016/j.bmcl.2008.07.043. Epub 2008 Jul 15.

PubMed ID

18674901 [ View in PubMed

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Abstract

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 34 nM, respectively) than captopril (IC(50); 630,000 nM).

DrugBank Data that Cites this Article

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
Captopril	Angiotensin-converting enzyme	IC 50 (nM)	23	N/A	N/A	Details
Captopril	Leukotriene A-4 hydrolase	IC 50 (nM)	14000	N/A	N/A	Details
Ubenimex	Leukotriene A-4 hydrolase	IC 50 (nM)	4000	N/A	N/A	Details