Synthesis and structure-activity relationships in a series of ethenesulfonamide derivatives, a novel class of endothelin receptor antagonists.

Abstract:

:In the previous paper, we described a series of the 2-arylethenesulfonamide derivatives, a novel class of ETA-selective endothelin (ET) receptor antagonists, including the compounds 1a, b. Compound 1a showed excellent oral antagonistic activities and pharmacokinetic profiles, and the monopotassium salt of 1 (YM-598 monopotassium) is in clinical trials. In this paper, we wish to report the investigation of the further details of structure-activity relationships (SARs) of the 2-phenylethenesulfonamide region in 1a. It was found that methyl substitutions at the 2-, 4- and 6-positions of the phenyl group in 1a led to the discovery of the ET(A)/ET(B) mixed antagonist (6s) with an IC50 of 2.2 nM for the ET(A) receptor. We also found that introduction of an ethyl group to the 1-position of the ethenyl group in 1a gave the ET(A) selective antagonist (6u) with an oral endothelin antagonistic activity in rats.

authors

Harada H,Kazami J,Watanuki S,Tsuzuki R,Sudoh K,Fujimori A,Tokunaga T,Tanaka A,Tsukamoto S,Yanagisawa I

doi

10.1248/cpb.49.1593

subject

Has Abstract

pub_date

2001-12-01 00:00:00

pages

1593-603

issue

12

eissn

0009-2363

issn

1347-5223

journal_volume

49

pub_type

杂志文章
  • Design, synthesis and biological evaluation of hydroxy- or methoxy-substituted phenylmethylenethiosemicarbazones as tyrosinase inhibitors.

    abstract::A series of hydroxy- or methoxy-substituted phenylmethylenethiosemicarbazones were designed, synthesized and evaluated as mushroom tyrosinase inhibitors. The results demonstrated that most of target compounds had remarkable inhibitory activities on mushroom tyrosinase. Interestingly, compound 2h was found to be the mo...

    journal_title:Chemical & pharmaceutical bulletin

    pub_type: 杂志文章

    doi:10.1248/cpb.57.1273

    authors: Yi W,Cao RH,Chen ZY,Yu L,Ma L,Song HC

    更新日期:2009-11-01 00:00:00

  • Structures and interaction with DNA of ternary palladium(II) complexes: [Pd(Gly)(X)] (Gly=glycine; X=2,2'-bipyridine, 1,10-phenanthroline and 2,2'-bi-pyridylamine).

    abstract::The structures of the ternary palladium(II) complexes of the formulations [Pd(Gly)(bpy)](+)Cl(-).4H(2)O (Gly=glycine; bpy=2,2'-bipyridine) (1), [Pd(Gly)(phen)](+)Cl(-).4H(2)O (2) (phen=1,10-phenanthroline) and {[Pd(Gly)(bpa)](+)Cl(-)}(2).6H(2)O (3) (bpa=2,2'-bipyridylamine) were determined. All complexes are positivel...

    journal_title:Chemical & pharmaceutical bulletin

    pub_type: 杂志文章

    doi:10.1248/cpb.56.908

    authors: Yodoshi M,Okabe N

    更新日期:2008-07-01 00:00:00

  • Site-specific cleavage of glycated human serum albumin in the presence of iron.

    abstract::Nonenzymatically glycated human serum albumin was incubated with ferric ion at 37 degrees C in 0.2 M phosphate buffer, pH 7.4, up to 30 days. In the incubation mixture, amino acids, tyrosine and phenylalanine, were detected, suggesting site specific cleavage of glycated human serum albumin. ...

    journal_title:Chemical & pharmaceutical bulletin

    pub_type: 杂志文章

    doi:10.1248/cpb.40.1653

    authors: Sakurai T,Takanashi M,Tsuchiya S

    更新日期:1992-06-01 00:00:00

  • Immunohistochemical demonstration of calcium-binding protein regucalcin in the tissues of rats: the protein localizes in liver and brain.

    abstract::A calcium-binding protein, regucalcin, was isolated from rat liver cytosol. Rabbit-anti-regucalcin antiserum, which was raised against regucalcin conjugated by glutaraldehyde to bovine serum albumin, was applied to glutaraldehyde-fixed whole mounts and subsequently visualized using the peroxidase-antiperoxidase method...

    journal_title:Chemical & pharmaceutical bulletin

    pub_type: 杂志文章

    doi:10.1248/cpb.39.1601

    authors: Yamaguchi M,Isogai M,Kato S,Mori S

    更新日期:1991-06-01 00:00:00

  • Studies on topical antiinflammatory agents. II. Synthesis and vasoconstrictive activity of 21-substituted corticosteroids with sulfur-containing moieties.

    abstract::As part of the search for new topical antiinflammatory agents, various 21-substituted corticosteroids having sulfur-containing moieties were prepared and tested for vasoconstrictive activity in humans. A structure-activity relationship study revealed that substitution of the 21-hydroxy group with a lower alkyl-thio gr...

    journal_title:Chemical & pharmaceutical bulletin

    pub_type: 杂志文章

    doi:10.1248/cpb.37.1795

    authors: Mitsukuchi M,Ikemoto T,Taguchi M,Higuchi S,Abe S,Yasui H,Hatayama K,Sota K

    更新日期:1989-07-01 00:00:00

  • Lithium Binaphtholate-Catalyzed Michael Reaction of Malonates with Maleates and Its Application to the Enantioselective Synthesis of Tricarboxylic Acid Derivatives.

    abstract::The Michael reaction of malonates with maleates afforded the corresponding adducts in high yields with high enantioselectivities (up to 98% enantiomeric excess (ee)) by using dilithium 3,3'-dichlorobinaphtholate as a catalyst. The obtained Michael adducts could be converted to optically active tricarboxylic acid (TCA)...

    journal_title:Chemical & pharmaceutical bulletin

    pub_type: 杂志文章

    doi:10.1248/cpb.c18-00993

    authors: Sakamoto M,Kaneko T,Orito Y,Shimoda Y,Nakajima M

    更新日期:2019-01-01 00:00:00

  • Highly selective cleavage of pyroglutamyl-peptide bond in concentrated hydrochloric acid.

    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

    authors: Hashimoto T,Saito S,Ohki K,Sakura N

    更新日期:1996-04-01 00:00:00

  • Sesquiterpenes from Ainsliaea fragrans and their inhibitory activities against cyclooxygenases-1 and 2.

    abstract::One new guaiane-type sesquiterpene glycoside, 2'-O-E-caffeoyl-8alpha-hydroxy-11alpha,13-dihydro-3beta-O-beta-D-glucozaluzanin C (1), was isolated from the whole herb of Ainsliaea fragrans (Compositae), together with five known sesquiterpene lactones: 8alpha-hydroxy-11alpha,13-dihydro-3beta-O-beta-D-glucozaluzanin C (2...

    journal_title:Chemical & pharmaceutical bulletin

    pub_type: 杂志文章

    doi:10.1248/cpb.57.597

    authors: Wang H,Wu T,Yan M,Liu G,Li P,Zhang XQ,Ye WC,Zhang LY

    更新日期:2009-06-01 00:00:00

  • Synthesis and Diels-Alder reactivity of ortho-carbazolequinones.

    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

    authors: Compain-Batissou M,Latreche D,Gentili J,Walchshofer N,Bouaziz Z

    更新日期:2004-09-01 00:00:00

  • Sulfonic acid functionalized silica: an efficient heterogeneous catalyst for a three-component synthesis of 1,4-dihydropyridines under solvent-free conditions.

    abstract::Sulfonic acid functionalized silica catalyzed the three-component reaction of aromatic amines, alpha,beta-unsaturated aldehydes and beta-keto esters forming the corresponding 1,4-dihydropyridines in short reaction times and in high yields. ...

    journal_title:Chemical & pharmaceutical bulletin

    pub_type: 杂志文章

    doi:10.1248/cpb.56.366

    authors: Das B,Suneel K,Venkateswarlu K,Ravikanth B

    更新日期:2008-03-01 00:00:00

  • Synthesis of N-substituted piperazinyl carbamoyl and acetyl derivatives of tetrahydropapaverine: potent antispasmodic agents.

    abstract::The synthesis and structure-activity-relationship (SAR) for a series of N-substituted piperazinyl carbamoyl 7-15 and piperazinyl acetyl 18-26 derivatives of tetrahydropapaverine have been carried out. The general synthetic methods of carbamoyl tetrahydropapaverine analogues involve N-substituted piperazines and carbam...

    journal_title:Chemical & pharmaceutical bulletin

    pub_type: 杂志文章

    doi:10.1248/cpb.50.1223

    authors: Kaur J,Ghosh NN,Talwar A,Chandra R

    更新日期:2002-09-01 00:00:00

  • 3-anilino-L-alanine, structural determination of UV-5, a contaminant in EMS-associated L-tryptophan samples.

    abstract::An aniline derivative which corresponds to UV-5 in the preceding paper was isolated from the case L-tryptophan sample associated with eosinophilia-myalgia syndrome (EMS). By spectroscopic analyses, the structure was identified as 3-anilinoalanine. The compound was optically active, and the stereochemistry of alanine m...

    journal_title:Chemical & pharmaceutical bulletin

    pub_type: 杂志文章

    doi:10.1248/cpb.40.2236

    authors: Goda Y,Suzuki J,Maitani T,Yoshihira K,Takeda M,Uchiyama M

    更新日期:1992-08-01 00:00:00

  • Studies on anti-inflammatory agents. V. Synthesis and pharmacological properties of 3-(difluoromethyl)-1-(4-methoxyphenyl)-5- [4-(methylsulfinyl)phenyl]pyrazole and related compounds.

    abstract::A series of novel 1,5-diphenylpyrazole derivatives bearing hydrophilic substituents was prepared. The anti-inflammatory and analgesic activities of these compounds were evaluated by using the adjuvant arthritis and Randall-Selitto assays in rats, and the structure-activity relationships were studied. The optimal compo...

    journal_title:Chemical & pharmaceutical bulletin

    pub_type: 杂志文章

    doi:10.1248/cpb.45.1475

    authors: Tsuji K,Konishi N,Spears GW,Ogino T,Nakamura K,Tojo T,Ochi T,Shimojo F,Senoh H,Matsuo M

    更新日期:1997-09-01 00:00:00

  • Solubility, dissolution rate and bioavailability enhancement of irbesartan by solid dispersion technique.

    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

    authors: Boghra RJ,Kothawade PC,Belgamwar VS,Nerkar PP,Tekade AR,Surana SJ

    更新日期:2011-01-01 00:00:00

  • Transport to intestinal lumen and peritoneal cavity of intravenously administered aprinidine in rats.

    abstract::Transfer of aprindine from the blood into the intestinal lumen or into the peritoneal cavity was examined after intravenous administration of the drug at a dose of 5 mg/kg in rats. The amount of the drug transferred from the blood into the intestinal lumen was much greater than into the peritoneal cavity. The average ...

    journal_title:Chemical & pharmaceutical bulletin

    pub_type: 杂志文章

    doi:10.1248/cpb.39.3359

    authors: Arimori K,Hashimoto Y,Nakano M

    更新日期:1991-12-01 00:00:00

  • Further metabolism of 3,5-di-tert-butyl-4-hydroxybenzoic acid, a major metabolite of butylated hydroxytoluene, in rats.

    abstract::The metabolic pathway of butylated hydroxytoluene (BHT) to the ring-oxygenated metabolites 2,6-di-tert-butylhydroquinone (BHQ) and 2,6-di-tert-butyl-p-benzoquinone (BBQ) was examined in rats. After intraperitoneal administration of 3,5-di-tert-butyl-4-hydroxybenzoic acid (BHT-acid), which had been regarded as one of t...

    journal_title:Chemical & pharmaceutical bulletin

    pub_type: 杂志文章

    doi:10.1248/cpb.39.512

    authors: Yamamoto K,Tajima K,Takemura M,Mizutani T

    更新日期:1991-02-01 00:00:00

  • Two new diterpenoids from cell cultures of Salvia miltiorrhiza.

    abstract::A new spiroketallactone, epi-danshenspiroketallactone A (1) and a new C18-norditerpenoid, normiltioane (2) along with 21 known compounds, were isolated from cell cultures of Salvia miltiorrhiza. Their structures were elucidated on the basis of extensive spectroscopic analyses. In the in vitro assays, the compounds 9-1...

    journal_title:Chemical & pharmaceutical bulletin

    pub_type: 杂志文章

    doi:10.1248/cpb.c12-00987

    authors: Zhang DW,Liu X,Xie D,Chen R,Tao XY,Zou JH,Dai J

    更新日期:2013-01-01 00:00:00

  • Molecular conformations of aminophenylimidazoles exhibiting antiulcer activities.

    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

    authors: Ishida T,In Y,Inoue M,Kurihara T,Moriomoto K,Morisaka K,Shibata K

    更新日期:1990-07-01 00:00:00

  • Formycin A resistant mutants due to defect in adenosine transport system in Vibrio parahaemolyticus.

    abstract::An antibiotic formycin A inhibited growth of Vibrio parahaemolyticus under certain conditions, which suggested that formycin A was taken up by cells under these conditions. We found that formycin A was transported via the adenosine transport system which we previously reported as a Na(+)-coupled cotransport system. We...

    journal_title:Chemical & pharmaceutical bulletin

    pub_type: 杂志文章

    doi:10.1248/cpb.39.1325

    authors: Sakai-Tomita Y,Mitani Y,Tsuda M,Tsuchiya T

    更新日期:1991-05-01 00:00:00

  • [2-(omega-phenylalkyl)phenoxy]alkylamines: synthesis and dual dopamine2 (D2) and 5-hydroxytryptamine2 (5-HT2) receptor antagonistic activities.

    abstract::A series of [2-(omega-phenylalkyl)phenoxy]alkylamines was synthesized and their 5-hydroxytryptamine2 (5-HT2) and/or dopamine2 (D2) receptor antagonistic activities were examined in vitro. [2-(4-Phenylbutyl)phenoxy]alkylamines showed strong inhibition of both 5-HT2 and D2 receptors. In particular, [2-(4-Phenylbutyl)phe...

    journal_title:Chemical & pharmaceutical bulletin

    pub_type: 杂志文章

    doi:10.1248/cpb.46.639

    authors: Tanaka N,Goto R,Ito R,Hayakawa M,Ogawa T,Fujimoto K

    更新日期:1998-04-01 00:00:00

  • Brominations of steroidal hormone having alpha,beta-unsaturated ketone, 17-O-acetyltestosterone, in the presence of silver triflate.

    abstract::Bromination of 17-O-acetyltestosterone (17beta-acetoxyandrost-4-en-3-one) (1) was performed with 1, 5, and 10 eq of Br2 in AcOH-Et2O at room temperature. In all cases 2alpha,6beta- (2) and 2alpha,6beta-dibromo-17beta-acetoxyandrost-4-en-3-one (3) were obtained, although the yields were dependent upon the conditions us...

    journal_title:Chemical & pharmaceutical bulletin

    pub_type: 杂志文章

    doi:10.1248/cpb.49.23

    authors: Shimizu T,Tobari A,Koyanagi J,Kawase M,Saito S

    更新日期:2001-01-01 00:00:00

  • 1,4-Benzoxazine-3(4H)-ones as potent inhibitors of platelet aggregation: design, synthesis and structure-activity relations.

    abstract::A series of novel potentially platelet aggregation-inhibiting 1,4-benzoxazine-3(4H)-one derivatives was designed and synthesized through Smiles rearrangement, reduction and acetylation reactions. The antiaggregatory activities of the target molecules on arterial blood samples from rabbits, expressed by IC₅₀ values (μM...

    journal_title:Chemical & pharmaceutical bulletin

    pub_type: 杂志文章

    doi:10.1248/cpb.c14-00330

    authors: Liu C,Tan JL,Xiao SY,Liao JF,Zou GR,Ai XX,Chen JB,Xiang Y,Yang Q,Zuo H

    更新日期:2014-01-01 00:00:00

  • Chiral Calcium-Catalyzed Asymmetric Epoxidation Reactions Using Hydrogen Peroxide as the Terminal Oxidant.

    abstract::Asymmetric epoxidation reactions of chalcone derivatives catalyzed by chiral calcium complexes using hydrogen peroxide were developed. The epoxidation reactions proceeded smoothly to afford the desired products in good yields with good enantioselectivities. This is the first example of chiral calcium-catalyzed asymmet...

    journal_title:Chemical & pharmaceutical bulletin

    pub_type: 杂志文章

    doi:10.1248/cpb.c18-00485

    authors: Yamashita Y,Macor JA,Fushimi S,Tsubogo T,Kobayashi S

    更新日期:2018-01-01 00:00:00

  • Studies on the preparation of bioactive lignans by oxidative coupling reaction. III. Synthesis of polyphenolic benzofuran and coumestan derivatives by oxidative coupling reaction of methyl (E)-3-(4-hydroxy-2-methoxyphenyl)propenoate and their inhibitory e

    abstract::Three dihydrobenzofuran derivatives 11, 19, 22, a Pummerer's ketone 20 and a dimeric phenylpropanoid 24 were synthesized by oxidative coupling reaction of methyl (E)-3-(4-hydroxy-2-methoxyphenyl)propenoate 10, which was prepared from umbelliferone. The major product 11 was converted into its acetate 21 and schizotenui...

    journal_title:Chemical & pharmaceutical bulletin

    pub_type: 杂志文章

    doi:10.1248/cpb.42.2536

    authors: Maeda S,Masuda H,Tokoroyama T

    更新日期:1994-12-01 00:00:00

  • Crystal structure of the alcoholates and the ansolvate of PNU-97018, an angiotensin II receptor antagonist.

    abstract::The title compound, PNU-97018 [systemic name: 2-butyl-3,6,7,8,9,11-hexahydro-6,9-dimethyl-3-([2'-(2H-tetrazol-5-yl)[1,1'-biphenyl]-4-yl]methyl)-6,9-ethano-4H-imidazo[4,5-d]-pyridazino[1,2-a]pyridazin-4-one] is a newly developed angiotensin II receptor antagonist. The compound and its methanolate and ethanolate were ch...

    journal_title:Chemical & pharmaceutical bulletin

    pub_type: 杂志文章

    doi:10.1248/cpb.50.1022

    authors: Ishii H,Yamaguchi K,Seki H,Sakamoto S,Tozuka Y,Oguchi T,Yamamoto K

    更新日期:2002-08-01 00:00:00

  • Determination of ornithine conjugates of some carboxylic acids in birds by high-performance liquid chromatography.

    abstract::A high-performance liquid chromatographic (HPLC) method for the determination of ornithine conjugation of some carboxylic acids in vitro has been developed. The ornithine conjugates of benzoic acid, p-nitrobenzoic acid, furancarboxylic acid and phenylacetic acid in an incubation mixture with kidney mitochondria were w...

    journal_title:Chemical & pharmaceutical bulletin

    pub_type: 杂志文章

    doi:10.1248/cpb.40.2196

    authors: Igarashi K,Suzuki R,Kasuya F,Fukui M

    更新日期:1992-08-01 00:00:00

  • Hypoglycemic effect of intestinally administered monosaccharide-modified insulin derivatives in rats.

    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

    authors: Haga M,Saito K,Shimaya T,Maezawa Y,Kato Y,Kim SW

    更新日期:1990-07-01 00:00:00

  • Intramolecular [2+2] cycloaddition of homoallylketenes to bicyclo[2.1.1]hexan-5-ones.

    abstract::Intramolecular [2+2] cycloaddition of γ,δ-unsaturated ketenes derived from hex-5-enoyl chloride derivatives gave bicyclo[2.1.1]hexan-5-ones with complete regioselectivity. ...

    journal_title:Chemical & pharmaceutical bulletin

    pub_type: 杂志文章

    doi:10.1248/cpb.60.548

    authors: Hoshikawa T,Tanji K,Matsuo J,Ishibashi H

    更新日期:2012-01-01 00:00:00

  • Platinum and palladium complexes containing ethylenediamine derivatives as carrier ligands and their antitumor activity.

    abstract::We prepared new antitumor active platinum complexes containing N,N'-bis(2-chloroethyl)ethylenediamine (ClEn) as an alkylating carrier ligand in order to obtain increased antitumor effects. Some of the platinum complexes synthesized showed enhanced antitumor activity. However, palladium(II) complexes containing ClEn we...

    journal_title:Chemical & pharmaceutical bulletin

    pub_type: 杂志文章

    doi:10.1248/cpb.42.702

    authors: Lee K,Tashiro T,Noji M

    更新日期:1994-03-01 00:00:00

  • Cimiracemoside a: A new cyclolanostanol xyloside from the rhizome of Cimicifuga racemosa.

    abstract::A new 9,19-cyclolanostane-type triterpene xyloside (1), from the rhizomes of Cimicifuga racemosa, has been isolated together with four known saponins; cimiaceroside A, 25-O-methylcimigenol-3-O-beta-D-xylopyranoside, 27-deoxyactein and 23-O-acetylshengmanol-3-O-beta-D-xylopyranoside. The structure of the new compound w...

    journal_title:Chemical & pharmaceutical bulletin

    pub_type: 杂志文章

    doi:10.1248/cpb.48.425

    authors: Bedir E,Khan IA

    更新日期:2000-03-01 00:00:00