Abstract:
:To develop non-prodrugs of taxoids with satisfactory stability in vivo, high water-solubility, and potent antitumor activity, we prepared several 10-O-sec-aminoethyl docetaxel analogs (3) and evaluated their cytotoxicity against mouse leukemia and human tumor cell lines, microtubule disassembly-inhibitory activity, and water-solubility. These analogs were synthesized from the 10-O-allyl baccatin derivatives (5a-c) using the beta-lactam synthon method. Among these analogs, the 10-O-(2-morpholinoethyl) (18, 21) and 10-O-(2-thiomorpholinoethyl) (19, 24) analogs exhibited cytotoxicity comparable or superior to that of docetaxel (2). In addition, the methanesulfonic acid salt (18a) had a high water-solubility.
journal_name
Chem Pharm Bull (Tokyo)journal_title
Chemical & pharmaceutical bulletinauthors
Uoto K,Takenoshita H,Yoshino T,Hirota Y,Ando S,Mitsui I,Terasawa H,Soga Tdoi
10.1248/cpb.46.770subject
Has Abstractpub_date
1998-05-01 00:00:00pages
770-6issue
5eissn
0009-2363issn
1347-5223journal_volume
46pub_type
杂志文章abstract::Analysis of the structural requirements of compound 1 (SR48968), a potent NK2 receptor antagonist, revealed that the 4-phenyl group of the piperidine is essential for binding with the NK2 receptor and occupies an equatorial position. Energy calculation of a variety of substituted 4-phenyl piperidines revealed that spi...
journal_title:Chemical & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/cpb.46.351
更新日期:1998-02-01 00:00:00
abstract::A series of substituted 6,7-dihydro-1-oxo-1H,5H-benzo[i,j]quinolizine-2-carboxylic acids was synthesized and tested for antibacterial activities. Among them, 9-fluoro-6,7-dihydro-5-methyl-8-(4-methyl-1-piperazinyl)-1-oxo-1H,5H- benzo[i,j]quinolizine-2-carboxylic acid (OPC-7241) exhibited potent antibacterial activity ...
journal_title:Chemical & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/cpb.37.2103
更新日期:1989-08-01 00:00:00
abstract::A chemical investigation of Jaspis sp., the marine sponge collected from the South China Sea led to the isolation of six new isomalabaricane-type compounds, jaspolides A-F (1-6). The structures of those compounds were elucidated by extensive spectroscopic methods. The structure-types of 1 to 6 could be classified into...
journal_title:Chemical & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/cpb.54.4
更新日期:2006-01-01 00:00:00
abstract::Improvement of solubility for fullerene (C60) was studied by cogrinding with cycloamyloses using a ball mill in the solid state. Cycloamylose is a novel cyclic alpha-1,4-glucan produced from synthetic amylose by enzymatic reaction. Although sample solutions showed a pale yellow for the initial period of cogrinding wit...
journal_title:Chemical & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/cpb.52.961
更新日期:2004-08-01 00:00:00
abstract::(+)-4(5)-[(2R,5R)-5-aminomethyltetrahydrofuran-2-yl]imidazole [(+)-1, imifuramine] and its 2R,5S-stereoisomer (+)-2 were expected as base compounds to develop selective human histamine H4-receptor ligands. The improved synthesis of (+)-1 was done via cyclization of a diazafulvene intermediate generated by Bu3P/N,N,N',...
journal_title:Chemical & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/cpb.51.832
更新日期:2003-07-01 00:00:00
abstract::The pharmacokinetics of [6]-gingerol were investigated in rats with acute renal failure induced by bilateral nephrectomy, or those with acute hepatic failure induced by a single oral administration of carbon tetrachloride (CCl4), to clarify the contribution of the kidney and liver to the elimination process of [6]-gin...
journal_title:Chemical & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/cpb.40.1295
更新日期:1992-05-01 00:00:00
abstract::A series of benzylamides of N-alkylated, N-acylated or free nine cyclic and one linear amino acids as potential anticonvulsants have been synthesized. The structures of the obtained compounds were designed on the basis of the previously determined structure and physicochemical properties/anticvonvulsant activity relat...
journal_title:Chemical & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/cpb.49.629
更新日期:2001-05-01 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::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::Three new glycosides, 7-deoxyloganic acid beta-D-glucopyranosyl ester (1), (3R)-hydrangenol 8,4'-di-O-beta-D-glucopyranoside (2), and (6R,7E,9R)-megastigma-4,7-dien-3-one 9,13-di-O-beta-D-glucopyranoside (3), have been isolated from the leaves of Hydrangea macrophylla subsp. serrata (THUNB.) MAKINO (Saxifragaceae). Th...
journal_title:Chemical & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/cpb.56.610
更新日期:2008-04-01 00:00:00
abstract::The purpose of the present study was the quantitative prediction of the bitterness-suppressing effect of sweeteners (sucrose or sugar alcohols) on the bitterness of famotidine (or quinine sulfate as control) solutions using an artificial taste sensor. Firstly, we examined the response characteristics of the sensor res...
journal_title:Chemical & pharmaceutical bulletin
pub_type: 临床试验,杂志文章
doi:10.1248/cpb.55.739
更新日期:2007-05-01 00:00:00
abstract::Present studies were undertaken on the preparation of synthetic analogues of bis- or tetra-coumarins and their activity against HIV-1 integrase (HIV-1 IN). Among these coumarin analogues, compounds 14, 16 and 18 were found to be potent molecules against HIV-1 IN at IC50 values of 0.96, 0.58, and 0.49 microM, respectiv...
journal_title:Chemical & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/cpb.55.1740
更新日期:2007-12-01 00:00:00
abstract::The aim of this study was to fabricate deformable chitosan (CS) microspheres for arterial embolization. CS microspheres containing poly(ethylene glycol) (PEG) were prepared by ionotropic gelation; PEG was then removed from the CS microspheres to produce the highly porous structure to allow deformability. The porosity ...
journal_title:Chemical & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/cpb.58.288
更新日期:2010-03-01 00:00:00
abstract::Novel 4,5,6,7-tetrahydrothieno[3,2-c]pyridines, 1-thienyl-1,2,3,4-tetrahydroisoquinolines and related compounds, in which the benzene rings of (+)-1 (FR115427) were replaced with heteroaromatic rings such as thiophene, furan, benzothiophene and indole, were synthesized and evaluated for anticonvulsant activity against...
journal_title:Chemical & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/cpb.44.778
更新日期:1996-04-01 00:00:00
abstract::To obtain optically active threo-2-amino-3-hydroxy-3-phenylpropanoic acid (1), (2RS,3SR)-2-benzoylamino-3-hydroxy-3-phenylpropanoic acid [(2RS,3SR)-2] was first optically resolved using (1S,2S)- and (1R,2R)-2-amino-1-(4-nitrophenyl)-1,3-propanediol as the resolving agents to afford (2R,3S)- and (2S,3R)-2 in yields of ...
journal_title:Chemical & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/cpb.51.1363
更新日期:2003-12-01 00:00:00
abstract::Indoloquinoline alkaloid cryptolepine and pyridocarbazole alkaloid ellipticine are of great interest because in vitro and in vivo studies revealed their good cytotoxic properties. In order to obtain some biologically active analogs of these compounds, we developed a synthesis based on the photocyclization of tertiary ...
journal_title:Chemical & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/cpb.55.1349
更新日期:2007-09-01 00:00:00
abstract::Various novel methotrexate (MTX) derivatives bearing an indoline moiety were synthesized and tested for biological activities using human peripheral blood mononuclear cell (hPBMC) and human synovial cells (hSC) derived from patients with rheumatoid arthritis (RA). Compounds having potent activity in vitro were further...
journal_title:Chemical & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/cpb.44.1332
更新日期:1996-07-01 00:00:00
abstract::An improved synthetic route has been developed for the preparation of methyl 1-fluoroindan-1-carboxylate (FICA Me ester) from 1-indanone. Methyl 4-methyl-1-fluoroindan-1-carboxylate (4-Me-FICA Me ester) was also prepared following the same procedure. ...
journal_title:Chemical & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/cpb.c14-00192
更新日期:2014-01-01 00:00:00
abstract::Diphenhydramine, a sedating antihistamine, is an agonist of human bitter taste receptor 14 (hTAS2R14). Diphenhydramine hydrochloride (DPH) was used as a model bitter medicine to evaluate whether the umami dipeptides (Glu-Glu and Asp-Asp) and their constituent amino acids (Glu, Asp) could suppress its bitterness intens...
journal_title:Chemical & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/cpb.c19-00736
更新日期:2020-01-01 00:00:00
abstract::Using tissue engineering technique to repair cartilage damage caused by osteoarthritis is a promising strategy. However, the regenerated tissue usually is fibrous cartilage, which has poor mechanical characteristics compared to hyaline cartilage. Chondrocyte hypertrophy plays an important role in this process. Thus, i...
journal_title:Chemical & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/cpb.c17-00225
更新日期:2017-01-01 00:00:00
abstract::Four hypotensive peptides called elapherine-A, -B, -C and -D were isolated from the body of Elaphe climacophora after removal of the internal organs. Elapherine-A, which had the lowest molecular weight, exhibited a prolonged fall for 5 min in the blood pressure of spontaneously hypertensive rats, whereas elapherin-B, ...
journal_title:Chemical & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/cpb.38.1004
更新日期:1990-04-01 00:00:00
abstract::The aim of the present study was to mask the bitterness of propiverine hydrochloride (P-4) by converting it to propiverine free base. Fine granules comprising the free base, which was converted from P-4 by desalination, were prepared. By using Fourier transform infrared spectroscopy, thermogravimetry-differential ther...
journal_title:Chemical & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/cpb.c12-00206
更新日期:2012-01-01 00:00:00
abstract::A new flavonol, morin-3-O-alpha-rhamnopyranoside (1), along with four known flavonols, kaempferol 3-O-alpha-rhamnopyranoside (2), kaempferol 3-O-beta-glucopyranoside (3), quercetin 3-O-alpha-rhamnopyranoside (4) and (+)-catechin (5), were isolated from the methanolic extract of Muehlenbeckia platyclada. The structures...
journal_title:Chemical & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/cpb.57.280
更新日期:2009-03-01 00:00:00
abstract::The discovery of a novel class of state-dependent voltage-gated sodium channel (NaV)1.7 inhibitors is described. By the modification of amide or urethane bond in NaV1.7 blocker III, structure-activity relationship studies that led to the identification of novel NaV1.7 inhibitor 2i (DS01171986) were performed. Compound...
journal_title:Chemical & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/cpb.c20-00126
更新日期:2020-01-01 00:00:00
abstract::The molecular geometry, acid dissociation constants and partition coefficients of the anilinoquinoline (I), indolo[3,2-c]quinoline (II) and tetrahydroindolo[3,2-d] [1]benzazepine (III) ring systems have been determined using representative compounds: 7-chloro-4-(p-anisidino)quinoline (Ia), 3-chloro-8-methoxy-11H-indol...
journal_title:Chemical & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/cpb.42.1084
更新日期:1994-05-01 00:00:00
abstract::We previously reported 2-[2-(4-tert-butylphenyl)ethyl]-N-(4-fluorophenyl)-1,2,3,4-tetrahydroisoquinoline-6-sulfonamide 2 as on orally available monoacylglycerol acyltransferase 2 (MGAT2) inhibitor which exhibited an in vivo efficacy at an oral dose of 100 mg/kg in a mouse oral lipid tolerance test. Further optimizatio...
journal_title:Chemical & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/cpb.c15-00803
更新日期:2016-01-01 00:00:00
abstract::The effect of regucalcin, a calcium-binding protein isolated from rat liver cytosol, on cytosolic Ca2+/calmodulin-dependent protein kinase activity was investigated. The increase in cytosolic Ca2+/calmodulin-dependent protein kinase activity with passage of incubation time was clearly prevented by the presence of regu...
journal_title:Chemical & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/cpb.38.2216
更新日期:1990-08-01 00:00:00
abstract::2-(5-Arylidene-4-oxo-3-phenyl-thiazolidin-2-ylidene)-3-oxo-propionitriles 4a-j were prepared via condensation of aromatic aldehydes with 4-thiazolidinones 3a,b. The latter was obtained via electrophilic attack of phenylisothiocyanate on 3-oxo-propionitriles 1a,b followed by reaction with chloroacetyl chloride under ba...
journal_title:Chemical & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/cpb.c12-00498
更新日期:2012-01-01 00:00:00
abstract::A series of 43 stilbene derivatives that showed cytotoxicity against human lung carcinoma (A549) was analyzed using comparative molecular field analysis (CoMFA) for defining the hypothetic pharmacophore model. The polyoxylated stilbenes were found to be active inhibitors of tubulin polymerization. Several cis-stilbene...
journal_title:Chemical & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/cpb.51.516
更新日期:2003-05-01 00:00:00
abstract::Six novel acyclic sulfides, named garlicnins L-1-L-4 (1-4), E (5), and F (6), were isolated from the acetone extracts, with the ability to suppress M2 macrophage activation, of the bulbs of garlic (Allium sativum L.), and their chemical structures were characterized. ...
journal_title:Chemical & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/cpb.c14-00003
更新日期:2014-01-01 00:00:00