Abstract:
:To find a novel acyl-CoA: cholesterol acyltransferase inhibitor, a series of sulfamide derivatives were synthesized and evaluated. Compound 1d, in which carboxymethyl moiety at the 5-position of Pactimibe was replaced by a sulfamoylamino group, showed 150-fold more potent anti-foam cell formation activity (IC(50): 0.02 microM), 1.6-fold higher log D(7.0) (4.63), and a slightly lower protein binding ratio (93.2%) than Pactimibe. Compound 1i, in which the octyl chain at the 1-position in 1d was replaced by an ethoxyethyl, showed markedly low log D(7.0) (1.73) and maintained 3-fold higher anti-foam cell formation activity (IC(50): 1.0 microM), than Pactimibe. The plasma protein binding ratio (PBR) of 1i was much lower than that of Pactimibe (62.5% vs. 98.1%), and its partition ratio to the rabbit atherosclerotic aorta after oral administration was higher than that of Pactimibe. Compound 1i at 10 microM markedly inhibited cholesterol esterification in atherosclerotic rabbit aortas even when incubated with serum, while Pactimibe had little effect probably due to its high PBR. In conclusion, compound 1i is expected to more efficiently inhibit the progression of atherosclerosis than Pactimibe.
journal_name
Chem Pharm Bull (Tokyo)journal_title
Chemical & pharmaceutical bulletinauthors
Takahashi K,Ohta M,Shoji Y,Kasai M,Kunishiro K,Miike T,Kanda M,Shirahase Hdoi
10.1248/cpb.58.1057subject
Has Abstractpub_date
2010-08-01 00:00:00pages
1057-65issue
8eissn
0009-2363issn
1347-5223pii
JST.JSTAGE/cpb/58.1057journal_volume
58pub_type
杂志文章abstract::Solifenacin (Sol), an antimuscarinic agent has been widely used for the treatment of overactive bladder. Transdermal formulations can be administered without water as well as absorbed slowly into the blood over a long period of time. The aim of this study was to develop cream and tape formulations of Sol, and evaluate...
journal_title:Chemical & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/cpb.c19-00552
更新日期:2019-01-01 00:00:00
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journal_title:Chemical & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/cpb.47.413
更新日期:1999-03-01 00:00:00
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journal_title:Chemical & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/cpb.58.402
更新日期:2010-03-01 00:00:00
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journal_title:Chemical & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/cpb.53.503
更新日期:2005-05-01 00:00:00
abstract::Alpha-trifluoromethyl allenol ethers 9a-e were prepared in moderate to good yields by the Julia-Lythgoe process using beta-ethoxy-beta-trifluoromethyl vinylic sulfone 3. Several reactions of 9c were examined to give alpha,beta-unsaturated trifluoromethyl ketone derivatives 11 and 12. ...
journal_title:Chemical & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/cpb.48.1395
更新日期:2000-09-01 00:00:00
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journal_title:Chemical & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/cpb.55.1175
更新日期:2007-08-01 00:00:00
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journal_title:Chemical & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/cpb.45.1163
更新日期:1997-07-01 00:00:00
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journal_title:Chemical & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/cpb.41.1846
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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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更新日期:2012-01-01 00:00:00
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journal_title:Chemical & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/cpb.c18-00220
更新日期:2018-01-01 00:00:00
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pub_type: 杂志文章
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更新日期:1995-10-01 00:00:00
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journal_title:Chemical & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/cpb.40.252
更新日期:1992-01-01 00:00:00
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journal_title:Chemical & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/cpb.c20-00359
更新日期:2020-01-01 00:00:00
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journal_title:Chemical & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/cpb.58.1532
更新日期:2010-11-01 00:00:00
abstract::In the search for a practical route to ornithine bisurethane derivatives useful for peptide synthesis, we elaborated the simple and efficient (86% yield) synthesis of N(epsilon)-tert-butoxycarbonyl-L-ornithine copper(II) complex (1). This served as substrate for obtaining N(epsilon)-tert-butoxycarbonyl-L-ornithine (2)...
journal_title:Chemical & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/cpb.49.1189
更新日期:2001-09-01 00:00:00
abstract::Fifteen triterpenoid saponins were isolated from the berries of Hedera colchica and their structures established on the basis of chemical and spectroscopic evidence. Among them, two are new compounds: coichiside A (3) and colchiside B (15) and four are described for the first time in the berries of Hedera colchica (co...
journal_title:Chemical & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/cpb.49.752
更新日期:2001-06-01 00:00:00
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journal_title:Chemical & pharmaceutical bulletin
pub_type: 杂志文章
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更新日期:2015-01-01 00:00:00
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journal_title:Chemical & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/cpb.48.1639
更新日期:2000-11-01 00:00:00
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journal_title:Chemical & pharmaceutical bulletin
pub_type: 杂志文章
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更新日期:1999-02-01 00:00:00
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journal_title:Chemical & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/cpb.39.512
更新日期:1991-02-01 00:00:00
abstract::Regioselectivity in N-acetylation of nitro-0-phenylenediamine, a widely used hair dye component, by rat liver cytosolic N-acetyltransferases was studied in relation to its substituent effects on enzymatic N-acetylation of mono-substituted anilines. Nitro-p-phenylenediamine was acetylated specifically at the N4-positio...
journal_title:Chemical & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/cpb.38.2561
更新日期:1990-09-01 00:00:00
abstract::Peptides mimicking chemokine receptor CCR5 were synthesized and their anti-HIV-1 activities evaluated. Prepared compounds, especially a sulfated derivatives, showed significant anti-HIV-1 activities. Furthermore, a hybrid molecule linked to an N-carbomethoxycarbonyl-prolyl-phenylalanine (CPF) moiety had a greater effe...
journal_title:Chemical & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/cpb.48.308
更新日期:2000-02-01 00:00:00
abstract::The full structures of the two steroidal saponins from Narthecium asiaticum MAXIM. We previously identified as toxic substances by monitoring the toxicity in guinea pigs were phytochemically reinvestigation on the aerial parts of the plant. The desired toxic saponins (6,7) were isolated together with two known lignan ...
journal_title:Chemical & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/cpb.43.1162
更新日期:1995-07-01 00:00:00
abstract::A new neolignan, (7R,8R)-5-O-demethylbilagrewin (1), together with four known lignans (2-5), were isolated from the heartwood of Santalum album (Santalaceae). The structure of 1 was determined by analysis of extensive spectroscopic data. The isolated compounds and derivatives were evaluated for their cytotoxic activit...
journal_title:Chemical & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/cpb.58.587
更新日期:2010-04-01 00:00:00
abstract::Two new C(21) steroidal glycosides, tenacissoside L (1), tenacissoside M (2), were isolated from the stems of Marsdenia tenacissima (ROXB.) WIGHT et ARN. Their structures were elucidated, respectively, by means of chemical and spectral data, including ESI-MS, HR-ESI-MS, 1D-NMR and 2D-NMR. ...
journal_title:Chemical & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/cpb.54.696
更新日期:2006-05-01 00:00:00
abstract::New triazine-type dehydrocondensing reagents, such as ROMP-Trz-Cl and ROMP(OH)-Trz-Cl, were synthesized by a ring opening metathesis polymerization (ROMP) method, and these showed higher loading than conventional polymer-supported condensing reagents. These polymers effect the formation of amides in good yields by add...
journal_title:Chemical & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/cpb.55.825
更新日期:2007-05-01 00:00:00
abstract::A pentacosapeptide corresponding to the entire amino acid sequence of Neurospora crassa metallothionein and several related cysteine-containing peptides were synthesized by the conventional solution method and their heavy metal-binding properties were examined. The Cu2+- or Cu+-binding properties of the various peptid...
journal_title:Chemical & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/cpb.37.2322
更新日期:1989-09-01 00:00:00
abstract::A model based on solubility parameters is proposed to predict the solubility curves of antihelmintic drugs at several temperatures, including aqueous and non-aqueous mixtures. The solubility of the drugs was measured in ethanol-water and ethanol-ethyl acetate mixtures at 15-35 degrees C (mebendazole) and at 25 degrees...
journal_title:Chemical & pharmaceutical bulletin
pub_type: 杂志文章
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更新日期:2010-05-01 00:00:00
abstract::The compound tentatively named TL-1 was isolated from Talaromyces luteus as a metabolite having monoamine oxidase (MAO) inhibitory potency. TL-1 showed mixed-type inhibition of MAO in mouse liver when kynuramine was used as a substrate, and the IC50 was 6.6 microM. The inhibition constants (Ki) for MAO-A and -B in mou...
journal_title:Chemical & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/cpb.37.206
更新日期:1989-01-01 00:00:00