Abstract:
:Herein we report the development of novel, potent and non-peptide luteinizing hormone releasing hormone (LHRH) antagonists. The optimization towards derivatives free from mechanism-based CYP3A4 inhibition is described. The identification of a main metabolite guided us towards structural modifications of the benzyl moiety, which resulted in significant improvements of the CYP3A4 profile, while maintaining potent LHRH antagonist activity.
journal_name
Chem Pharm Bull (Tokyo)journal_title
Chemical & pharmaceutical bulletinauthors
Hashimoto K,Kataoka M,Tatsuta M,Yasoshima K,Yamamoto M,Yura T,Yamamoto N,Urbahns K,Gupta JB,Li Ydoi
10.1248/cpb.53.1314subject
Has Abstractpub_date
2005-10-01 00:00:00pages
1314-7issue
10eissn
0009-2363issn
1347-5223pii
JST.JSTAGE/cpb/53.1314journal_volume
53pub_type
杂志文章abstract::A new pregnane glycoside, a dibenzylbutyrolactone lignan, 5-hydroxymatairesinol dimethyl ether, and three new flavonoids, including one 8-methylflavan-3-ol, and two 8-methylflavones, together with five known flavonoids and two known alkaloids were isolated from the rhizomes of Tupistra chinensis. The structures of all...
journal_title:Chemical & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/cpb.54.954
更新日期:2006-07-01 00:00:00
abstract::Four new bicyclic hexapeptides, named as RA-XI, -XII, XIII and -XIV were isolated from Rubia cordifolia and showed potent antitumor activities against P-388. The structures were elucidated from spectroscopic and chemical evidences. RA-XII, XIII and -XIV were proved to be unique bicyclic hexapeptidic glucosides. ...
journal_title:Chemical & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/cpb.40.1352
更新日期:1992-05-01 00:00:00
abstract::Synthesis of (1R,2S,5S,6R,8S)-3-azabicyclo[3.3.0]octane-2,6,8-tricarboxylic acid (2) from trans-4-hydroxy-L-proline (5) was attempted. A Diels-Alder reaction of 3,4-dehydroproline derivative 9 and cyclopentadiene afforded a single stereoisomer 11. The Diels-Alder adduct was smoothly converted to the hydrochloride of 2...
journal_title:Chemical & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/cpb.51.1015
更新日期:2003-08-01 00:00:00
abstract::Vanadate stimulated the release of rat hepatic lipase activity from liver slices into an incubation medium in a time- and dose-dependent manner. Insulin, however, failed to have this stimulatory action, and the release by heparin was recognized, but was not additive to that by vanadate. Amiloride, an inhibitor of tyro...
journal_title:Chemical & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/cpb.39.3287
更新日期:1991-12-01 00:00:00
abstract::UV-Irradiation of taxinine and related compounds in acetonitrile induced a smooth transannulation between the C-3 and C-11 positions without any influence from the C-2, C-9 and C-10 substituents to give tetracyclic taxuspine C derivatives in almost quantitative yields. Photochemical transannular reaction of taxoids po...
journal_title:Chemical & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/cpb.46.1135
更新日期:1998-07-01 00:00:00
abstract::Three metabolites of N-[2-(1-azabicyclo[3.3.0]octan-5-yl)ethyl]-2-nitroaniline fumarate (SK-946), a novel central muscarinic cholinergic receptor agonist, were prepared to confirm their proposed structures, and tested for muscarinic receptor affinity in vitro. ...
journal_title:Chemical & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/cpb.47.880
更新日期:1999-06-01 00:00:00
abstract::Soluble (SSG, beta-1,3-D-glucan obtained from the culture filtrates of a fungus, Sclerotinia sclerotiorum IFO 9395) and particulate (zymosan) beta-glucans were oxidized by sodium hypochlorite (NaClO), and the oxidized products were analyzed by gel filtration and ion-exchange chromatographies and by limulus G-test to s...
journal_title:Chemical & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/cpb.44.2137
更新日期:1996-11-01 00:00:00
abstract::Three novel cantharidin analogues were isolated from the Chinese blister beetle, Mylabris phalerata PALL. (Meloidae), which has been used in traditional Chinese medicine for the treatment of cancer. Their structures were determined on the basis of heteronuclear multiple-bond connectivity and nuclear Overhauser effect ...
journal_title:Chemical & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/cpb.52.807
更新日期:2004-07-01 00:00:00
abstract::The objective of present work was to enhance the solubility and bioavailability of poorly aqueous soluble drug Irbesartan (IBS). The solid dispersions were prepared by spray drying method using low viscosity grade HPMC E5LV. Prepared solid dispersions were characterized by dissolution study, fourier transform infrared...
journal_title:Chemical & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/cpb.59.438
更新日期:2011-01-01 00:00:00
abstract::Allylamine (ALAM) film was plasma-polymerized on a flat glass (referred to as ALAM(GLA): GLA refers to a flat glass plate) for use as a solid phase in two-site immunoradiometric assay (two-site IRMA). Adsorption of F(ab')2 anti-human immunoglobulin G [formula: see text] to ALAM(GLA) was larger than adsorption on a pol...
journal_title:Chemical & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/cpb.40.501
更新日期:1992-02-01 00:00:00
abstract::The Stille coupling reaction of the stannylindole 13 with the 5-iodoimidazole derivative 14 (or 27) in the presence of PdCl(2)(PPh(3))(2) gave the corresponding indole-imidazole coupling product 15 (or 28), thereby affording a synthetic approach to 10-methylgranulatimide (7), 15-methylgranulatimide (11), and 10, 15-di...
journal_title:Chemical & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/cpb.51.209
更新日期:2003-02-01 00:00:00
abstract::Tumor necrosis factor related apoptosis-inducing ligand (TRAIL) has emerged as a promising anticancer agent as it selectively kills cancer cells. However, TRAIL resistance limits its use as a therapeutic agent. An understanding the mechanisms responsible for TRAIL resistance and strategies to overcome it are important...
journal_title:Chemical & pharmaceutical bulletin
pub_type: 杂志文章,评审
doi:10.1248/cpb.c15-00732
更新日期:2016-01-01 00:00:00
abstract::The rates of release of nicotinamide (NAA) from fatty acid (FA)-NAA complexes, FA-NAA, were determined at various temperatures, and the thermodynamic quantities for the release of NAA were estimated. The results were compared with the previous results obtained for FA-thiamine disulfide (TDS) complexes, (FA)6(TDS). The...
journal_title:Chemical & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/cpb.39.3114
更新日期:1991-12-01 00:00:00
abstract::An efficient stereocontrolled total synthesis of (+)-biotin (1) has been achieved via the intermediacy of Roche's lactone 5 starting from cis-1,3-dibenzyl-2-imidazole-4,5-dicarboxylic acid (2). The bifunctional cinchona alkaloid-derived squaramide-promoted enantioselective alcoholysis was utilizing as a tool for the c...
journal_title:Chemical & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/cpb.59.488
更新日期:2011-01-01 00:00:00
abstract::A moisturizing cream mixed with a steroid ointment is frequently prescribed to patients suffering from atopic dermatitis. However, there is a concern that the mixing operation causes destabilization. The present study was performed to investigate the stability of such preparations closely using magnetic resonance imag...
journal_title:Chemical & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/cpb.c16-00986
更新日期:2017-01-01 00:00:00
abstract::We have attempted to prepare micronized drug particles and to maintain the micronized state long-term in order to improve the solubility of a practically insoluble drug, griseofulvin (GF). GF nanoparticles (GFNPs) prepared by high-pressure homogenization were micronized to about 45 nm (mean particle size). GFNPs were ...
journal_title:Chemical & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/cpb.54.181
更新日期:2006-02-01 00:00:00
abstract::C1q/tumor necrosis factor (TNF)-related protein 12 (CTRP12) is a secretory protein that participates in the regulation of glucose and lipid metabolism in obesity and diabetes. Its role in cardiovascular disease, particularly sepsis-induced cardiac injury, is unclear. Here, we stimulated cardiomyocytes with lipopolysac...
journal_title:Chemical & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/cpb.c19-00646
更新日期:2020-01-01 00:00:00
abstract::The synthesis and biological evaluation of [2-Valine-A] insulin ([Val2-A]insulin) is reported. In this insulin, the isoleucine residue in position A2, invariant in the majority of mammalian insulins, is substituted by valine. The same substitution, along with four others, occurs naturally in the insulin produced by th...
journal_title:Chemical & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/cpb.37.670
更新日期:1989-03-01 00:00:00
abstract::Chemical investigation of the soft coral Sinularia leptoclados has afforded three new sesquiterpenoids, leptocladols A (1), B (2), and 1-epi-chabrolidione A (3). The relative structures of 1-3 were determined on the basis of extensive spectroscopic analysis. The relative configuration of 1 was further confirmed by a s...
journal_title:Chemical & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/cpb.58.250
更新日期:2010-02-01 00:00:00
abstract::It is well-known that baicalin-berberine complex (1) precipitates in the water decoction of numerous Chinese Medicinal formulae containing Radix Scutellariae and Rhizoma Coptidis or Cortex Phellodendri. In the current study, ionic interaction between the carboxylate ion of baicalin and the quaternary ammonium ion of b...
journal_title:Chemical & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/cpb.60.706
更新日期:2012-01-01 00:00:00
abstract::The effect of the modification of insulin (INS) with p-succinylamidophenyl (SA)-alpha-D-glucopyranoside (SAPG), SA-alpha-D-mannopyranoside and SA-alpha-L-arabinopyranoside on the enzymatic degradation and the hypoglycemic effect in rats was studied. When SAPG-INS was administered intraintestinally in the absence of bi...
journal_title:Chemical & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/cpb.38.1983
更新日期:1990-07-01 00:00:00
abstract::In an investigation of a new class of deoxyribonucleic acid (DNA)-intercalating antitumor agents, novel acridinyl-substituted uracils have been synthesized and evaluated for activity against L1210 leukemia in vivo, and against bacteria and fungus. These compounds were prepared by the novel enamine reaction between 9-c...
journal_title:Chemical & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/cpb.37.697
更新日期:1989-03-01 00:00:00
abstract::The n-BuOH extract of Swertia japonica showed a significant hepatoprotective effect on D-galactosamine (D-GalN)/lipopolysaccharide (LPS)-induced liver injury in mice. The activity-guided fractionation led to the isolation of a new tetrahydroxanthone derivative, tetrahydroswertianolin (1), as well as two known iridoids...
journal_title:Chemical & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/cpb.45.1823
更新日期:1997-11-01 00:00:00
abstract::The manufacture of highly drug-loaded fine globular granules eventually applied for orally disintegrating tablets has been investigated using a unique multi-functional rotor processor with acetaminophen, which was used as a model drug substance. Experimental design and statistical analysis were used to evaluate potent...
journal_title:Chemical & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/cpb.c14-00687
更新日期:2015-01-01 00:00:00
abstract::The release properties of phenylpropanolamine hydrochloride (PPA) from ethylcellulose (EC) matrix granules prepared by an extrusion granulation method were examined. The release process could be divided into two parts; the first and second stages were analyzed by applying square-root time law and cube-root law equatio...
journal_title:Chemical & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/cpb.52.298
更新日期:2004-03-01 00:00:00
abstract::Three new oleanane-type saponins, giganteosides L (1), M (2) and N (3) along with eight known ones were isolated from the roots of Cephalaria gigantea. Their structures were established as 3-O-[beta-D-galactopyranosyl-(1-->2)-beta-D-glucuronopyranosyl]-28-O-[beta-D-glucopyranosyl-(1-->6)-beta-D-glucopyranosyl]-oleanol...
journal_title:Chemical & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/cpb.55.102
更新日期:2007-01-01 00:00:00
abstract::A fragment analog, [D-Arg30]prothymosin alpha fragment 1-30, containing D-arginine in place of arginine residue at position 30 was synthesized by the liquid phase procedure and studied for immunological effect on the impaired blastogenic response of T-lymphocytes isolated from uremic patients after treatment of human ...
journal_title:Chemical & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/cpb.39.752
更新日期:1991-03-01 00:00:00
abstract::Electrochemical oxidation of catechols in the presence of phenyl-Meldrum's acid as a nucleophile in aqueous solution has been studied in detail by means of cyclic voltammetry and controlled potential coulometry. The results indicate that the o-benzoquinone derived from catechols participates in Michael addition reacti...
journal_title:Chemical & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/cpb.58.23
更新日期:2010-01-01 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::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): 0.0...
journal_title:Chemical & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/cpb.58.1057
更新日期:2010-08-01 00:00:00