Novel 5-Hydroxytryptamine (5-HT_3) Receptor Antagonists. Synthesis and Structure-Activity Relationships of 9-Methyl-2,3,4,9-tetrahydrothiopyrano[2,3-b]indol-4-one Derivatives

スポンサーリンク

概要

• 論文の詳細を見る

• Novel 9-methyl-4,9-dihydrothiopyrano[2,3-b]indol-4-one derivatives 2b-e, 3-methylene-9-methyl-2,3,4,9-tetrahydrothiopyrano[2,3-b]indol-4-one derivatives 3b-e and 9-methyl-2,3,4,9-tetrahydrothiopyrano[2,3-b]indol-4-one derivatives 4a-e were prepared. The 5-hydroxytryptamine (5-HT_3) receptor-antagonistic activities of these compounds were evaluated by using the von Bezold-Jarisch reflex test (B. J. reflex, rats) and the contractile response to 5-HT in the isolated distal colon (guinea pig). The 5-ethyl-4-imidazolyl derivative 4d was found to be 79 times more potent than ondansetron 1 in the B. J. reflex test (ID_<50>=0.048 μg/kg, i.v.), and the 5-methyl-4-imidazolyl derivative 4c was found to be 126 times more potent than 1 in the colonic contraction (IC_<50>=0.0062 μM) assay.

• 公益社団法人日本薬学会の論文
• 1997-01-15

著者

• 斎藤 徹

  Faculty Of Pharmaceutical Sciences Kanazawa University

• Miyata K

  Yamanouchi Pharmaceutical Co. Ltd. Ibaraki Jpn

• Miyata K

  Yamanouchi Pharmaceutical Co. Ltd. Tsukuba City Jpn

• Miyata Keiji

  Inflammation Research Pharmacology Laboratories Institute For Drug Discovery Research Yamanouchi Pha

• Miyata Keiji

  Neuroscience/gastrointestinal Research Laboratories Institute For Drug Discovery Research Yamanouchi

• Suzuki T

  Drug Discovery Research Laboratory Sanwa Kagaku Kenkyusho Co. Ltd.

• 増田 明

  富山医科薬科大学麻酔科

• Suzuki T

  Laboratory Of Biopharmaceutics Faculty Of Pharmaceutical Sciences Chiba University

• Ohta Masato

  Pharmaceutical Research Center Meiji Seika Kaisha Ltd.

• Yanagisawa I

  Yamanouchi Pharmaceutical Co. Ltd. Ibaraki Jpn

• Yanagisawa Isao

  Institute For Drug Discovery Research Yamanouchi Pharmaceutical Co.

• Yanagisawa Isao

  山之内製薬

• Saito Takako

  Research And Development Laboratories Maruho Co. Ltd.

• Miyata Keiji

  Neuroscience And Gastrointestinal Research Laboratory Institute For Drug Discovery Research Yamanouc

• Matsuhisa Akira

  Gastrointestinal Research Laboratories Institute For Drug Discovery Research Yamanouchi Pharmaceutic

• Suzuki Toshikazu

  Discovery Research Laboratory Tanabe Seiyaku Co. Ltd.

• Ohta Miyako

  Division Of Biological Chemistry And Biologicals National Institute Of Health Sciences

• Miyata K

  Institute For Drug Discovery Research Yamanouchi Pharmaceutical Co.

• Ohta Mitsuaki

  Neuroscience/gastrointestinal Research Laboratories Institute For Drug Discovery Research Yamanouchi

• Miyata K

  Inflammation Research Pharmacology Laboratories Institute For Drug Discovery Research Yamanouchi Pha

• SUZUKI Takeshi

  Neuroscience and Gastrointestinal Research Laboratory, Institute for Drug Discovery Research, Yamano

• Suzuki T

  Research Unit Of Pharmaceutics College Of Pharmacy Nihon University

• Miyata K

  Hitachi Research Laboratory Hitachi Ltd.

• YANAGISAWA Isao

  Gastrointestinal Research Laboratories, Institute for Drug Discovery Research, Yamanouchi Pharmaceut

• Suzuki Takeshi

  Neuroscience And Gastrointestinal Research Laboratory Institute For Drug Discovery Research Yamanouchi Pharmaceutical Co. Ltd.

• Miyata Keiji

  Neuroscience & Gastrointestinal Research Laboratories, Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co., Ltd.

関連論文

• Purines. LXIX. Direct N(1)-Oxidation of 7-Benzyladenine and Stepwise Syntheses of Its N(1)- and N(3)-Oxides
• Purines. LXVII. An Alternative Synthesis of Adenine 7-Oxide : N-Oxidation of the Adenine Ring Utilizing Blocking/Deblocking at the 1-Position
• Purines. LXVI. Adenine 7-Oxide : Its Synthesis, Chemical Properties, and X-ray Molecular Structure
• Purines. LII. Synthesis and Biological Evaluation of 8-Methylguanine 7-Oxide and Its 9-Arylmethyl Derivatives
• Purines. LI. Synthesis and Biological Activity of Hypoxanthine 7-N-Oxide and Related Compounds
• Purines. L. Synthesis and Antileukemic Activity of the Antibiotic Guanine 7-Oxide and Its 9-Substituted Derivatives
• 2-(3-Pyridyl)thiazolidine-4-carboxamide Derivatives. II. Structure-Activity Relationships and Active Configuration of 2-(3-Pyridyl)thiazolidine-4-carboxamides as Platelet-Activating Factor Receptor Antagonists
• 2-(3-Pyridyl)thiazolidine-4-carboxamides. 1. Novel Orally Active Antagonists of Platelet-Activating Factor (PAF)
• Purines. LX. Dimroth Rearrangement and Concomitant Hydrolytic Deamination of 7-Alkyl-1-methyladenines
• Involvement of a Cytochrome P4502D Subfamily in Human Liver Microsomal Bunitrolol 4-Hydroxylation
• Synthesis and Biological Activity of the Metabolites of N-[2-(1-Azabicyclo[3.3.0]octan-5-yl)ethyl]-2-nitroaniline Fumarate (SK-946)
• Synthesis of (1-Azabicyclo[3.3.0]octanyl)methyl-Substituted Aromatic Heterocycles and Their Muscarinic Activity
• Synthesis and Thromboxane A_2 Antagonistic Activity of [[1-Aryl(or Benzyl)-1-(benzenesulfonamide)methyl]phenyl]alkanoic Acid Derivatives
• Laxative and Anti-diarrheal Activity of Polycarbophil in Mice and Rats
• An Improved Synthesis of Butyl 4-[(4-Amino-5-chloro-2-methoxybenzoyl)amino]-1-piperidineacetate (AU-224)
• Synthesis and Gastrointestinal Prokinetic Activity of Novel Benzamide Derivatives with Amphoteric Side Chains
• Calcium Polycarbophil, a Water Absorbing Polymer, Increases Bowel Movement and Prevents Sennoside-Induced Diarrhea in Dogs
• Purines. XLI. : An Alternative Synthesis and the Chemical Behavior of 7,9-Dialkyladeninium Salts
• Purines. XXXVIII. A General Synthesis of 7,9-Dialkyladeninium Salts from 9-Alkyladenines by Regioselective Alkylation : Utilization of an N^6-Alkoxy Group as a Control Synthon
• Purines. XXX. : Ring Fission of 3,7-Dialkyladenines by Alkaline Hydrolysis
• Purines. XXVIII. Preparation of Some 3,7-Dialkyladenines from 3-Alkyladenines by Alkylation : A Subordinate Formation of 3,9-Dialkyladenines
• Purines. XXI. Synthesis of Adenine 1-Oxides Carrying an Allylic Side Chain at the 9-Position
• Decalcification of Calcium Polycarbophil in Rats
• Structure-Activity Relationship(SAR)Studies on Oxazolidinone Antibacterial Agents.1. Conversion of 5-Substituent on Oxazolidinone
• Cytotoxicity of Organochlorine Pesticides and Lipid Peroxidation in Isolated Rat Hepatocytes
• Cytotoxicity of Organochlorine Pesticides and Lipid Peroxidation in Rat Hepatocytes (Proceedings of the 22nd Symposium on Toxicology and Environmental Health)
• Cytotoxicity of Paraquat and Phospholipid Peroxidation in Rat Hepatocytes (Proceedings of the 21st Symposium on Toxicology and Environmental Health)
• Cytotoxicity of Halogenated Hydrocarbons and Cellular Phospholipid Peroxidation in Isolated Rat Hepatocytes (Proceedings of the 20th Symposium on Toxicology and Environmental Health)
• Characterization of the Neurochemical Effects of N-[2-(1-azabicyclo[3,3,0]octan-5-yl)ethyl]2-nitroaniline fumarate (SK-946) as a Cognition Activator
• P-3 海綿由来アデニン環含有ジテルペノイドの合成研究 : (±)-Agelasimine-Aおよび(±)-Agelasimine-Bの合成(ポスター発表の部)
• Purines. LXV. Preparatory study for the syntheses of the marine sponge purines agelasimines-A and -B: Synthesis and acetylation of their N(7)-benzyl analogues
• Purines. LXIV. Syntheses of 9-Methyl-2-azaadenine 1-Oxide, Its O-Methyl Derivative, and 1-Substituted 5-Azidoimidazole-4-carboxamides
• Purines. LXIII. Syntheses of Azepinomycin, an Antitumor Antibiotic from Streptomyces Species, and Its 3-β-D-Ribofuranodise and Their 8-Imino Analogues
• Purines. LXI. An Attempted Synthesis of 2'-Deoxy-7-methyladenosine : Glycosidic Hydrolyses of the N^6-Methoxy Derivative and 2'-Deoxy N^x-methyladenosines
• Purines. LIX. An Alternative Synthesis of 7-Alkyl-1-methyladenines by Regioselective Alkylation, Fission, and Reclosure of the Adenine Ring
• Purines. LVIII. A Synthesis of 7-Alkyl-1-methyladenines from Adenosine by Regioselective Alkylation : Uilization of a 1-Methoxy Group as a Control Synthon
• Purines. LVII. Regioselective Alkylation of N^6,9-Disubstituted 8-Oxoadenines : Syntheses of the Sea Anemone Purine Caissarone and Some Positional Isomers and Analogues
• Purines. LIV. Intramolecular Cyclization of 9-Ethyl-1-(2-hydroxyethyl)adenine Caused by Nucleophiles : Formation of N^6,1-Ethanoadenine Derivatives
• Purines. LIII. Deamination of 1-(ω-Hydroxyalkyl)adenine Derivatives by Nucleophiles
• Purines. XLIX. Synthesis and Proton Nuclear Magnetic Resonance Study of 3,7-Dialkylxanthines and 1,3,7-Trialkylxanthines
• Purines. XLVIII. Syntheses and Proton Nuclear Magnetic Resonance Study of 2-Deuterioadenines Substituted or Unsubstituted at the 9-Position and of Their N-Oxygenated Derivatives
• Purines. XLVI. Preparation of 1-Ethyladenine from Adenosine
• Immunoliposome-Mediated Gene Transfer into Cultured Myotubes
• Examination of Local Anti-inflammatory Activities of New Steroids, Hemisuccinyl Methyl Glycolates
• Application of Sweet Potato Fiber to Skin Wound in Rat
• Gastroprokinetic Effect of a New Benzamide Derivative Itopride and Its Action Mechanisms in Conscious Dogs
• Synthesis of 5-(Alkylamino)-1-β-D-ribofuranosyl-1H-imidazole-4-carboxamides : Key Intermediates for the Synthesis of 3-Alkyl-9-β-D-ribofuranosylpurine Derivatives
• Purines. XXXII. : Synthesis and Ring Fission of 3,9-Dialkyladenines
• Purines. XXV. Fission and Reclosure of the Adenine Ring by the Use of Modified Benzyloxy Groups at the 1-Position
• Purines. XXII. Methylation of 1-, 3-, 7-, 9-, and N^6-Methyladenines Bearing a Methoxyl Group at the N^6-Position : A Synthesis of 7,9-Dimethyladenine
• Purines. XX. Synthesis of 1-Substituted 5-Aminoimidazole-4-carboxamidines and Related Compounds
• Modification by Fluoride, Bromide, Iodide, Thiocyanate and Nitrite Anions of Reaction of a Myeloperoxidase-H_2O_2-Cl^- System with Nucleosides
• Effects of Fluvastatin and Its Major Metabolites on Low-Density Lipoprotein Oxidation and Cholesterol Esterification in Macrophages
• Fluvastatin, an HMG-CoA Reductase Inhibitor, Protects LDL from Oxidative Modification in Hypercholesterolemic Rabbits
• In Vitro Inhibitory Effects of the Optical Isomers and Metabolites of Fluvastatin on Copper Ion-Induced LDL Oxidation
• An in Vitro Study of the Hydroxyl Radical Scavengin Property of Fluvastatin, and HMG-CoA Reductase Inhibitor
• Biological Activity of Analogues of YM022. Novel (3-Amino Substituted Phenyl)urea Derivatives of 1,4-Benzodiazepin-2-one as Gastrin : Cholecystokinin-B Receptor Antagonists
• In Vivo Pharmacologic Profile of YM158, a New Dual Antagonist for Leukotriene D_4 and Thromboxane A_2 Receptors
• Effect of YM158, a Dual Lipid Mediator Antagonist, on Immediate and Late Asthmatic Responses, and on Airway Hyper-responsiveness in Guinea Pigs
• Effect of Serotonin (5 - HT)_3 - Receptor Antagonists YM060, YM114 (KAE - 393), Ondasetron and Granisetron on 5 - HT_4 Receptors and Gastric Emptying in Rodents
• Protective Effect of a Pancreatic Elastase Inhibitor Against a Variety of Acute Pancreatitis in Rats
• Pancreatic Enzyme-Induced Pancreatitis and Systemic Complications in Rats
• Species Differences in the 5-Hydroxytryptamine-Induced Contraction in the Isolated Distal Ileum
• Characteristics of Inhibitory Effects of Serotonin (5-HT)_3 - Receptor Antagonists, YM060 and YM114 (KAE - 393), on the von Bezold - Jarisch Reflex Induced by 2 - Methyl - 5 - HT, Veratridine and Electrical Stimulation of Vagus Nerves in Anesthetized Rats
• Studies on Serotonin (5-HT)_3-Receptor Antagonist Effects of Enantiomers of 4,5,6,7-Tetrahydro-1H-Benzimidazole Derivatives
• YM-40461 Improves Airway Clearance in Guinea Pigs with Induced Subacute Bronchitis
• 2-(3-Pyridyl)thiazolidine-4-carboxamide Derivatives. III. Synthesis of Metabolites and Metabolism of 2-(3-Pyridyl)thiazolidine-4-carboxamides YM461 and YM264 as Platelet-Activating Factor (PAF) Receptor Antagonists
• Purines. XLVII. Dimroth Rearrangement versus Hydrolytic Deamination of 1-Ethyladenine
• Synthesis of [[(Benzenesulfonamido)alkyl]phenyl]alkanoic Acid Derivatives Containing Pyridyl or Imidazolyl Groups and Their Thromboxane A_2 Receptor Antagonistic and Thromboxane A_2 Synthase Inhibitory Activities
• Synthesis of the Selective 5-Hydroxytryptamine 4 (5-HT_4) Receptor Agonist (+)-(S)-2-Chloro-5-methoxy-4-[5-(2-piperidylmethyl)-1,2,4-oxadiazol-3-yl]aniline
• Intramolecular Oxymercuration with Mercuric Triflate
• Mercuric Triflate-TMU Catalyzed Hydration of Terminal Alkyne to give Methyl Ketone under Mild Conditions
• Effects of N-[2-(1-Azabicyclo[3,3,0]octan-5-yl)ethyl]2-nitroaniline Fumarate (SK-946), a Novel Cognition Activator, on Learning and Memory in Rodent Models
• Novel 5-Hydroxytryptamine 4 (5-HT_4) Receptor Agonists. Synthesis and Gastroprokinetic Activity of 4-Amino-N-[2-(1-aminocycloalkan-1-yl)ethyl]-5-chloro-2-methoxybenzamides
• Purines. XXXVII. : Synthesis and Reduction of 3,9-Diallkyladenine Salts Deuterated at the 2-Position : Their Use in the Proton Nuclear Magnetic Resonance Study of Isotopically Unmodified Species
• Purines.XXXIX. : The Crystal Structure of 9-Benzyl-N^6-methoxyadenine
• Purines. XXXI. : An X-Ray Crystallographic Structure Analysis of 3-Methyladenosine p-Toluenesulfonate
• Novel 5-Hydroxytryptamine (5-HT_3) Receptor Antagonists. Synthesis and Structure-Activity Relationships of 9-Methyl-2,3,4,9-tetrahydrothiopyrano[2,3-b]indol-4-one Derivatives
• Novel 5-Hydroxytryptamine (5-HT_3) Receptor Antagonists. IV. Synthesis and Pharmacological Evaluation of the Oxidation Products of (-)-(R)-5-[(1-Methyl-1H-indol-3-yl)carbonyl]-4,5,6,7-tetrahydro-1H-benzimidazole Hydrochloride (YM060 : Ramosetron)
• Novel 5-Hydroxytryptamine (5-HT_3) Receptor Antagonists. III. Pharmacological Evaluations and Molecular Modeling Studies of Optically Active 4,5,6,7-Tetrahydro-1H-benzimidazole Derivatives
• Novel 5-Hydroxytryptamine (5-HT_3) Receptor Antagonists. II. Synthesis and Structure-Activity Relationships of 4,5,6,7-Tetrahydro-1H-benzimidazole Derivatives
• Novel 5-Hydroxytryptamine (5-HT_3) Receptor Antagonists. I. Synthesis and Structure-Activity Relationships of Conformationally Restricted Fused Imidazole Derivatives
• Purines. XLIV. : A Kinetic Study of the Dimroth Rearrangement of the Marine Sponge Purine 1,9-Dimethyl-8-oxoadenine and Related Compounds
• Purines. XLIII. : A Total Synthesis of the Marine Sponge Base 6-Imino-1,9-dimethyl-8-oxopurine
• 53 桿菌tRNA構成成分,7-Methyladenosineの合成と加水分解(口頭発表の部)
• Purines. XLII. : Synthesis and Glycosidic Hydrolysis of 7-Alkyladenosines Leading to an Alternative Synthesis of 7-Alkyladenines
• Purines. XL. : Preparation of 9-(ω-Carboxyalkyl)-3-methyladenines
• Purines. XXXVI. : Fission and Reclosure of the Adenine Ring in 3,9-Disubstituted Adenines : Effects of Substituents
• Purines. XXXIV. : 3-Methyladenosine and 3-Methyl-2'-deoxyadenosine : Their Synthesis, Glycosidic Hydrolysis, and Ring Fission
• A General and Convenient Synthesis of 7-Alkyladenines from Adenine by Regioselective Alkylation Utilizing Blocking/Deblocking at the 3-Position
• Purines. XXVII. : Hydrolytic Deamination versus Dimroth Rearrangement in the 9-Substituted Adenine Ring : Effect of an ω-Hydroxyalkyl Group at the 1-Position
• Purines. XXVI. The Dimroth Rearrangement of 9-Substituted 1-Methyladenines : Accelerating Effect of a β-D-Ribofuranosyl Group at the 9-Position
• Purines. XXIV. Methylation of N^6-Alkoxyadenines and N^6-Methyladenine
• Purines. XXIII. Synthesis of N^6-Alkoxy-1,3-dialkyladeninium Salts and an Attempt to Synthesize 1,3-Dimethyladenine
• Purines. XIII. Ring Opening of 3-Alkyladenines with Carbobenzoxy Chloride : Transformation into 8-Hydroxylated Adenines
• Purines. X. A Convenient Method for Synthesis of 2', 3'-O-Isopropylidene-adenosine 1-Oxide
• Purines. XVIII. Kinetic Studies of the Dimroth Rearrangement of 1-Alkoxy-9-methyladenines and 1-Benzyloxyadenosine : Effect of 1-Benzyloxy and 9-β-D-Ribofuranosyl Groups on the Rates of the Ring-opening and the Reclosure
• Effect of a Novel Non-steroidal Anti-inflammatory Drug (M-5011) on Cytokine Levels in Rats With Monosodium Urate Crystal-Induced Pleurisy
• Purines. XI. The Synthesis of N-Alkoxyadenosines and Their 2', 3'-O-Isopropylidene Derivatives
• Cytotoxicity of Chlorinated Hydrocarbons and Lipid Peroxidation in Isolated Rat Hepatocytes (Proceedings of the 19th Symposium on Toxicology and Environmental Health)

もっと見る 閉じる

スポンサーリンク