Structure-activity relationship study and drug profile of N-(4-fluorophenylsulfonyl)-L-valyl-L-leucinal (SJA6017) as a potent calpain inhibitor

被引：57

作者：

Inoue, J

Nakamura, M

Cui, YS

Sakai, Y

Sakai, O

Hill, JR

Wang, KKW

Yuen, PW

机构：

[1] Senju Pharmaceut Co Ltd, Kobe Creat Ctr, Nishi Ku, Kobe, Hyogo 6512241, Japan

[2] Ricerca LLC, Concord, OH 44077 USA

[3] Pfizer Global Res & Dev, Ann Arbor Labs, Neurosci Therapeut, Ann Arbor, MI 48105 USA

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2003年 / 46卷 / 05期

关键词：

D O I：

10.1021/jm0201924

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Novel N-arylsulfonyldipeptidyl aldehyde derivatives were prepared by DMSO oxidation from the corresponding dipeptide alcohol, and their potencies as calpain inhibitors were evaluated in vitro. Among them, N-(4-fluorophenylsulfonyl)-L-valyl-L-leucinal (8, SJA6017) potently inhibited calpains. 8 also inhibited cathepsin B and L but did not inhibit other cysteine proteases (interleukin 1beta-converting enzyme), serine proteases (trypsin, chymotrypsin, thrombin, factor VIIa, factor Xa), or proteasome. Preliminary cytotoxicity studies of 8 exhibited a relatively safe profile.

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页码：868 / 871

页数：4

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