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

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

Author information

1
Nara Research & Development Center, Santen Pharmaceutical Co., Ltd, 8916-16, Takayama-cho, Ikoma-shi, Nara 630-0101, Japan. hiroshi.enomoto@santen.co.jp

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).

PMID:
18674901
DOI:
10.1016/j.bmcl.2008.07.043
[Indexed for MEDLINE]

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