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Start Over Author "Fumio, Tsuji" Journal bioorganicmedicinal chemistry letters
2 results on '"Fumio, Tsuji"'

1. Synthesis and pharmacological evaluation of 1,1,3-substituted urea derivatives as potent TNF-alpha production inhibitors

Author

Chikako Setoguchi, Hiroyuki Inoue, Yoshimasa Sasabuchi, Ayako Sawa, Noriyoshi Yamamoto, Masahiro Okamoto, Hiroshi Suhara, Hiroshi Enomoto, Fumio Tsuji, Masakazu Ban, and Masato Horiuchi

Subjects
Lipopolysaccharide, Stereochemistry, Pyridines, Tumor Necrosis Factor-alpha, Organic Chemistry, Clinical Biochemistry, Substituent, Pharmaceutical Science, Administration, Oral, Biochemistry, Chemical synthesis, Sulfenic Acids, Proinflammatory cytokine, Rats, chemistry.chemical_compound, chemistry, Oral administration, Drug Discovery, Urea, Molecular Medicine, Moiety, Animals, Tumor necrosis factor alpha, Molecular Biology
Abstract

A three substituted urea derivative, SA13353 (compound 1a), exhibited potent inhibitory activity against lipopolysaccharide (LPS)-induced TNF-alpha production. We focused on the 1,1-substituted moiety (R(1) and R(2)) of SA13353 and investigated substituent effects of this moiety on LPS-induced TNF-alpha production by oral administration in rats. The synthesis of the urea derivatives was performed rapidly in a one-pot manner using a manual synthesizer. Several compounds containing hydrophobic substituents at this moiety showed more potent inhibitory activities than SA13353.

Published
2010

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

Author

Fumio Tsuji, Masakazu Ban, Yurika Miyake, Masato Horiuchi, Ken-Ichi Fujimura, Maki Mizuchi, Hiroshi Suhara, Yuko Morikawa, and Hiroshi Enomoto

Subjects
Proline, Stereochemistry, Carboxylic acid, Chemistry, Pharmaceutical, Clinical Biochemistry, Carboxylic Acids, Pharmaceutical Science, Crystallography, X-Ray, Biochemistry, Chemical synthesis, Leukotriene-A4 hydrolase, chemistry.chemical_compound, Inhibitory Concentration 50, Structure-Activity Relationship, Drug Discovery, Hydrolase, Animals, Humans, Sulfhydryl Compounds, Epoxide hydrolase, Molecular Biology, chemistry.chemical_classification, Epoxide Hydrolases, Leukotriene A4, Organic Chemistry, chemistry, Models, Chemical, Microsomal epoxide hydrolase, Drug Design, Molecular Medicine, Thiazolidines
Abstract

We studied the synthetic modification of structurally similar N-mercaptoacyl- l -proline and (4R)-N-mercaptoacylthiazolidine-4-carboxylic acid to obtain potent leukotriene A4 (LTA4) 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 C4 position of proline yielded much more potent LTA4 hydrolase inhibitors (IC50; 52, 31, and 34 nM, respectively) than captopril (IC50; 630,000 nM).

Published
2008

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