Abstract:
:Beauveriolides I and III, which are naturally occurring cyclodepsipeptides, have been reported to bind to sterol O-acyltransferase (SOAT), inhibiting its ability to synthesize cholesteryl esters. To facilitate an analysis of the binding site(s) of these compounds, we designed beauveriolide analogues 1a-d wherein the Leu or D-allo-Ile residue was replaced by photoreactive amino acids possessing methyldiazirine or trifluoromethyldiazirine in the side chains. The methyldiazirine moiety was installed by reaction of methyl ketones with liquid ammonia to provide imine intermediates, followed by treatment with hydroxylamine-O-sulfonic acid to provide the diaziridines. Subsequent oxidation gave methyldiazirines. In contrast, trifluoromethyldiazirine derivatives were prepared from trifluoromethyl ketones via the oxime intermediates, which were transformed into diaziridines. Subsequent oxidation afforded trifluoromethyldiazirines. The synthesized photoreactive amino acids 3a-d were coupled with 3-hydroxy-4-methyloctanoic acid 4 and dipeptide 5, followed by macrolactamization to provide beauveriolide analogues 1a-d. The SOAT inhibitory activities of 1a-d were found to be as potent as those of beauveriolides I and III. Moreover, 1a-d inhibited SOAT1 selectively rather than SOAT2, which was also consistent with the behavior of beauveriolides I and III.
journal_name
Chem Pharm Bull (Tokyo)journal_title
Chemical & pharmaceutical bulletinauthors
Masuda Y,Aoyama K,Yoshida M,Kobayashi K,Ohshiro T,Tomoda H,Doi Tdoi
10.1248/cpb.c16-00095subject
Has Abstractpub_date
2016-07-01 00:00:00pages
754-65issue
7eissn
0009-2363issn
1347-5223journal_volume
64pub_type
杂志文章abstract::To experimentally clarify a possible stereostructure-activity relationship proposed for H2-receptor antagonists, three 5-aminophenylimidazoles (1, 2 and 3), in which respective amino groups are located on the ortho, meta and para positions of the benzene ring, were synthesized and examined for their conformational cha...
journal_title:Chemical & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/cpb.38.1803
更新日期:1990-07-01 00:00:00
abstract::New five seven-membered vibsane-type diterpenes named 5-epi-vibsanin C, 5-epi-vibsanin H, 5-epi-vibsanin K, 18-O-methyl-5-epi-vibsanin K and 5-epi-vibsanin E have been isolated from the leaves of Viburnum awabuki (Caplifoliaceae). Their structures have been elucidated by analyses of spectroscopic data and comparison o...
journal_title:Chemical & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/cpb.50.368
更新日期:2002-03-01 00:00:00
abstract::A series of diarylureas and diarylamides possessing pyrrolo[2,3-d]pyrimidine scaffold was designed and synthesized. The in vitro antiproliferative activities of a selected group of the target compounds against NCI-60 cell line panel were tested and compared with Sorafenib and Imatinib as reference compounds. Most of t...
journal_title:Chemical & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/cpb.c13-00249
更新日期:2014-01-01 00:00:00
abstract::Highly selective cleavage reaction of pGlu-peptide bond is described. Two model peptides, pGlu-X-Ala-Phe-OH (X = Ile and Ser), and dog neuromedin U-8 (d-NMU-8) (1-7)-OH (pGlu-Phe-Leu-Phe-Arg-Pro-Arg-OH) were hydrolyzed in concentrated HCl at 0 degree C for from 6 days to 6 weeks to give the predominant cleavage produc...
journal_title:Chemical & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/cpb.44.877
更新日期:1996-04-01 00:00:00
abstract::N-Terminal tripeptide analogs of fibrin alpha-chain were synthesized and their inhibitory effect on fibrinogen/thrombin clotting was examined. A new water-soluble active ester, 3-pyridinium ester, was used for the synthesis. Among the synthetic peptides, H-Gly-Pro-Arg-hexamethyleneimine exhibited the highest inhibitor...
journal_title:Chemical & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/cpb.39.584
更新日期:1991-03-01 00:00:00
abstract::The hydrolysis of protopanaxadiol-type saponin mixture by various glycoside hydrolases was examined. Among these enzymes, crude preparations of lactase from Aspergillus oryzae, beta-galactosidase from A. oryzae, and cellulase from Trichoderma viride were found to produce ginsenoside F(2) [3-O-(beta-D-glucopyranosyl)-2...
journal_title:Chemical & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/cpb.55.1522
更新日期:2007-10-01 00:00:00
abstract::Two sesterterpenes, deoxymanoalide (1) and deoxysecomanoalide (2), were isolated from the nudibranch Chromodoris willani collected in Okinawa and their structures determined on the basis of spectroscopic data and chemical conversions. The mollusk feeds on a sponge containing manoalide (3) and secomanoalide (4) and is ...
journal_title:Chemical & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/cpb.57.885
更新日期:2009-08-01 00:00:00
abstract::Particles of poorly water-soluble drugs were prepared to develop a dry powder inhaler (DPI). Spray freeze-drying (SFD) technique using a four-fluid nozzle (4N), which has been developed by authors, was applied in this research. Ciclosporin and mannitol were used as a poorly water-soluble model drug and a dissolution-e...
journal_title:Chemical & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/cpb.c12-00208
更新日期:2012-01-01 00:00:00
abstract::Novel cyclic sulfoxides, such as 2-octyl, 2-dodecyl and 2-hexadecyltetrahydrothiophene-1-oxide were prepared by the alkylation of tetrahydrothiophene-1-oxide. Additionally, 2-methyl, 2-ethyl and 2-propyl-5-dodecyltetrahydro-thiophene-1-oxide were conducted by further alkylation. Their enhancing activity on the penetra...
journal_title:Chemical & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/cpb.40.1961
更新日期:1992-07-01 00:00:00
abstract::We have identified a novel cardiac steroid, 11,19-epoxy-19-methoxytelocinobufagin, named marinosin (1), in the skin of the toad, Bufo marinus (L.) Schneider. The treatment of compound 1 with 50% CH3CN containing 0.1% trifluoroacetic acid yielded a 11 alpha-hydroxyhellebrigenin (2), which has not previously been isolat...
journal_title:Chemical & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/cpb.45.249
更新日期:1997-02-01 00:00:00
abstract::Study was carried out to develop two simple, fast, accurate and sensitive spectrophotometric methods (A and B) for the determination of citalopram hydrobromide in commercial tablet formulations. In method A, UV spectrophotometer determined the contents of citalopram hydrobromide in tablets at 240 nm in methanol solven...
journal_title:Chemical & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/cpb.54.432
更新日期:2006-04-01 00:00:00
abstract::Stereoselective synthesis of the 16-membered diolide 27, a fully functionalized congener of lepranthin (1), is described. The requisite five asymmetric carbon centers in monomer 23 were constructed in a highly stereoselective manner by using different epoxide-opening reactions of α,β-unsaturated γ,δ-epoxy esters and e...
journal_title:Chemical & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/cpb.59.525
更新日期:2011-01-01 00:00:00
abstract::The characteristic diagram for refolding of denatured reduced lysozyme was prepared in terms of recovered activity by employing urea and LiCl concentrations as two axes of rectangular coordinates. The diagram obtained will serve as a new tool not only for the optimum design of refolding media but also for the study of...
journal_title:Chemical & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/cpb.43.2027
更新日期:1995-11-01 00:00:00
abstract::To find candidates with high antimicrobial and low hemolytic activities, many gramicidin S (GS) analogs of various ring sizes have been designed and synthesized. However, syntheses of antimicrobially active analogues of GS having a disordered symmetry structure from C(2) have almost never been reported, because the st...
journal_title:Chemical & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/cpb.59.1481
更新日期:2011-01-01 00:00:00
abstract::A new sesquiterpene 2,9-humuladien-6-ol-8-one (1) was isolated from methanol extract of Zingiber aromaticum, along with 15 known compounds. The structures of the isolated compounds were elucidated on the basis of spectroscopic analyses. The isolated compounds were tested for their inhibitory activity on the metabolism...
journal_title:Chemical & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/cpb.53.333
更新日期:2005-03-01 00:00:00
abstract::The purpose of this study was to develop and test a novel and simple method for evaluating the disintegration time of rapidly disintegrating tablets (RDTs) in vitro, since the conventional disintegration test described in the pharmacopoeia produces poor results due to the difference of its environmental conditions fro...
journal_title:Chemical & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/cpb.c13-00441
更新日期:2013-01-01 00:00:00
abstract::Two monomethylated GM(3)-Type ganglioside molecular species, 1 and 2, have been obtained from the polar lipid fraction of the chloroform/methanol extract of the starfish Luidia maculata. The structures of these gangliosides have been determined on the basis of chemical and spectroscopic evidence as 1-O-[8-O-methyl-(N-...
journal_title:Chemical & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/cpb.50.1386
更新日期:2002-10-01 00:00:00
abstract::Electron spin resonance studies showed that addition of rat liver microsomes to the reaction system of alloxan with reduced nicotinamide adenine dinucleotide phosphate (NADPH) resulted in a marked increase in the generation of alloxan radicals (AH.), whereas heat-denatured microsomes were without such effect. Oxidatio...
journal_title:Chemical & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/cpb.40.432
更新日期:1992-02-01 00:00:00
abstract::A novel macrocyclic diterpene, jatrophenone, has been isolated from the whole plant of Jatropha gossypifolia. The structure of the compound was established by detailed studies of its one- and two-dimensional (1D and 2D) NMR spectra. The compound possesses significant antibacterial activity. ...
journal_title:Chemical & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/cpb.51.870
更新日期:2003-07-01 00:00:00
abstract::From the leaves of Cananga odorata var. odorata, three relatively large molecules, namely two aryl naphthalene lignan diesters of canangafruticoside A and one cyclobutane lignan diester of canangafruticoside A, were isolated along with four known compounds. The structures of the new compounds were elucidated based on ...
journal_title:Chemical & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/cpb.c16-00611
更新日期:2017-01-01 00:00:00
abstract::Acetohydroxy acid synthase (AHAS; EC 2.2.1.6, also referred to as acetolactate synthase, ALS) has been considered as an attractive target for the design of herbicides. In this work, an optimized pyrazole sulfonamide base scaffold was designed and introduced to derive novel potential AHAS inhibitors by introducing a py...
journal_title:Chemical & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/cpb.c17-00761
更新日期:2018-01-01 00:00:00
abstract::Oxidation of 2- and 3-hydroxycarbazoles with Frémy's salt gave the corresponding ortho-carbazolequinones. These molecules react as carbodienophiles in Diels-Alder reaction with 1-acetoxy-1,3-butadiene and 1,3-cyclopentadiene to provide the novel benzocarbazolequinone structures 15, 16, 18 and 19. ...
journal_title:Chemical & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/cpb.52.1114
更新日期:2004-09-01 00:00:00
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
doi:10.1248/cpb.40.343
更新日期:1992-02-01 00:00:00
abstract::A new cytotoxic substance, designated russuphelin A (1), has been isolated from the mushroom Russula subnigricans Hongo (Basidiomycetes). The structure was elucidated as 2,6-bis(2,6-dichloro-4-hydroxyphenyloxy)-1,4-dimethoxy-benzene on the basis of spectroscopic data and confirmed by total synthesis. ...
journal_title:Chemical & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/cpb.40.3185
更新日期:1992-12-01 00:00:00
abstract::In our series of studies on potassium channel openers, several thienylcyanoguanidine derivatives were synthesized and evaluated for smooth muscle relaxation activity in vitro. Among the newly synthesized compounds, N-cyano-N'-(5-cyano-3-thienyl)-N"-tert-pentylguanidine (4b) and N-(5-bromo-3-thienyl)-N'-cyano-N"-tert-p...
journal_title:Chemical & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/cpb.45.2005
更新日期:1997-12-01 00:00:00
abstract::It has been indicated that hydrophilic solid powder to which aqueous solution of a novel dehydrocondensing reagent DMT-MM is adsorbed becomes a simple solid-phase dehydrocondensing reagent of low cost. Reaction in a liquid--liquid biphasic system on the surface of a solid phase with a large area was accelerated by sus...
journal_title:Chemical & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/cpb.52.1223
更新日期:2004-10-01 00:00:00
abstract::We discovered that the reactivity of some conjugated and electron-deficient hydrocarbons was quite different in the presence of transition metal catalysts. In this review we report our development and applications of the highly selective palladium and nickel-catalyzed cycloaddition reactions of unsaturated hydrocarbon...
journal_title:Chemical & pharmaceutical bulletin
pub_type: 杂志文章,评审
doi:10.1248/cpb.53.1069
更新日期:2005-09-01 00:00:00
abstract::A new series of 11-substituted 6,11-dihydrodibenz[b,e]oxepin derivatives was synthesized and evaluated for antiallergic activity. Convenient methods for the preparation of sulfides from alcohols were developed. Structure-activity relationships are described. Compound 7, 11-[2-(dimethylamin)ethyl]thio-6,11-dihydrodiben...
journal_title:Chemical & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/cpb.39.2724
更新日期:1991-10-01 00:00:00
abstract::Racemic 1-acetoxy-2-phenylpropane (12) and 1-acetoxy-2-(2-naphthyl)propane (33) were hydrolyzed with lipase at 35-36 degrees C for 2 and 24 h to give predominantly (S)-2-phenyl-1-propanol (11) and (S)-2-(2-naphthyl)-1-propanol (32), respectively. However, racemic 1-acetoxy-2-(1-naphthyl)propane (25) was recovered inta...
journal_title:Chemical & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/cpb.42.1191
更新日期:1994-06-01 00:00:00
abstract::Scale-up of wet granulation in a vertical high shear mixer was conducted. Pharmaceutical excipient powders composed of lactose, cornstarch and micro-crystallinecellulose, and hydroxypropylcellulose as a binder were mixed together and then granulated with purified water under various operating conditions and vessel sca...
journal_title:Chemical & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/cpb.53.351
更新日期:2005-04-01 00:00:00