Abstract:
:This study demonstrates the structure-activity relationship of Col-003, a potent collagen-heat-shock protein 47 (Hsp47) interaction inhibitor. Col-003 analogues were successfully synthesized by Pd(0)-catalyzed cross-coupling reactions of 5-bromosalicylaldehyde derivatives with alkyl-metal species, and the inhibitory activities of the synthetic analogues were evaluated using surface plasmon resonance analysis (BIAcore). We succeeded in discovering two potent inhibitors that showed 85 and 81% inhibition at a concentration of 1.9 µM against the collagen-Hsp47 interaction. This indicates that elongation of an alkyl linker between two aromatic rings could considerably improve inhibitory activity due to the adjustment of a pendant phenyl moiety to an appropriate position, in addition to the hydrophobic interaction with an alkyl linker moiety.
journal_name
Chem Pharm Bull (Tokyo)journal_title
Chemical & pharmaceutical bulletinauthors
Yoshida M,Saito M,Ito S,Ogawa K,Goshima N,Nagata K,Doi Tdoi
10.1248/cpb.c19-00634subject
Has Abstractpub_date
2020-03-01 00:00:00pages
220-226issue
3eissn
0009-2363issn
1347-5223journal_volume
68pub_type
杂志文章abstract::A full account is given of the first chemical synthesis of the antitumor antibiotic guanine 7-oxide (5) and its 9-substituted derivatives (24a--k and 26). Coupling of appropriate primary amines (17a--e, g--k) with phenacyl bromide (16) produced, after treatment with HCl, the corresponding N-substituted phenacylamine h...
journal_title:Chemical & pharmaceutical bulletin
pub_type: 杂志文章
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更新日期:1992-02-01 00:00:00
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journal_title:Chemical & pharmaceutical bulletin
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journal_title:Chemical & pharmaceutical bulletin
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journal_title:Chemical & pharmaceutical bulletin
pub_type: 杂志文章
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journal_title:Chemical & pharmaceutical bulletin
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更新日期:2001-09-01 00:00:00
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journal_title:Chemical & pharmaceutical bulletin
pub_type: 杂志文章
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journal_title:Chemical & pharmaceutical bulletin
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journal_title:Chemical & pharmaceutical bulletin
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journal_title:Chemical & pharmaceutical bulletin
pub_type: 杂志文章
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journal_title:Chemical & pharmaceutical bulletin
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pub_type: 杂志文章
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journal_title:Chemical & pharmaceutical bulletin
pub_type: 杂志文章
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journal_title:Chemical & pharmaceutical bulletin
pub_type: 杂志文章
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journal_title:Chemical & pharmaceutical bulletin
pub_type: 杂志文章
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journal_title:Chemical & pharmaceutical bulletin
pub_type: 杂志文章
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journal_title:Chemical & pharmaceutical bulletin
pub_type: 杂志文章
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journal_title:Chemical & pharmaceutical bulletin
pub_type: 杂志文章
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journal_title:Chemical & pharmaceutical bulletin
pub_type: 杂志文章
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abstract::The title compounds, together with 3-vinylindolizine-1-carbonitriles (4-56%), were prepared in 1-18% yields from the S-alkylation of pyridinium 1-[3-ethoxycarbonyl-1-[cyanomethylthio(thiocarbonyl)]]all ylides with alkyl halides, followed by treatment of the resulting pyridinium salts with a base and then a dehydrogena...
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