Synthesis and Sedative-Hypnotic Effects of N^3-Allyl-and N^1-Allyl-5,6-substituted 2-Thiouracil Derivatives in Mice

スポンサーリンク

概要

• 論文の詳細を見る

• Twenty four thiouracil derivatives, including N^3-allyl- (19) and N^1-allyl-2-thiouracil (20) were synthesized and their pharmacological effects [sedative-hypnotic activity (loss of righting reflex and spontaneous activity), convulsant activity, effect on pentobarbital (PB)-induced sleep and mortality] were evaluated in mice at doses of 320 mg/kg, i.p. and 2 μmol/mouse by intracerebroventricular (i.c.v.) injections, respectively. N^3-Allyl-6-propyl-2-thiouracil (3), N^3-allyl-5,6-dimethyl-2-thiouracil (10), N^3-allyl-1,2,3,4,5,6,7,8,9-nonahydro-4-oxo-2-thiocyclohepta[d]pyrimidine (16) and N^3-allyl-5-methyl-2-thiouracil (18) exhibited sedative-hypnotic activity, whereas N^3-allyl-6-ethyl-5-methyl-2-thiouracil (11), N^1-allyl-5-methyl-2-thiouracil (21), N^1-allyl-1,2,3,4,5,6,7,8,9-nonahydro-4-oxo-2-thiocyclohepta[d]pyrimidine (23) and N^1-allyl-5,6-dimethyl-2-thiouracil (24) conversely displayed clonic- and/or tonic-convulsant seizures. N^3-Allyl-6-propyl-2-thiouracil (3) and N^3-allyl-5-methyl-2-thiouracil (18) decreased spontaneous activity. Other compounds examined were inactive, or only slightly active in the sedative-hypnotic assay even at high doses. Fifteen compounds (1-4,7,10,11,14-16,18-21,and 23) significantly prolonged the PB-induced sleeping time. Interestingly, only N^1-allyl-5,6-dimethyl-2-thiouracil (24) shortened the PB-induced sleeping time. These results showed that these thiouracils possessed many different effects such as sedative-hypnotic, anticonvulsant and/or convulsant, and that N^3-allyl-5-methly-2-thiouracil (18) and N^1-allyl-5,6-dimethyl-2-thiouracil (24) had the most potent hypnotic activity and antagonistic effect against PB, respectively.

• 社団法人日本薬学会の論文
• 1998-09-15

著者

• 景山 節

  京大・霊長類研・生化学

• Yamamoto Ikuo

  Department Of Hygienic Chemistry School Of Pharmaceutical Sciences Kyushu University Of Health And W

• Yamamoto Ikuo

  Faculty of Education, Yokohama National University

• Kondo Shigemi

  Nissui Pharmaceutical Co. Ltd.

• WATANABE Kazuhito

  Faculty of Pharmaceutical Sciences, Hokuriku University

• KIMURA Toshiyuki

  Faculty of Pharmaceutical Sciences, Hokuriku University

• HO Ing

  University of Mississippi Medical Center

• DRAMINSKI Marcin

  Institute of Basic Sciences, Military School of Medicine

• TURSKI Krzysztof

  Institute of Basic Sciences, Military School of Medicine

• TATEOKA Yuji

  Faculty of Pharmaceutical Sciences, Hokuriku University

• 舘岡 裕二

  Shinshin Chemical Industry Co. Ltd.

• Yamamoto Ikuo

  北陸大学 薬 衛化

• YAMAMOTO IKUO

  Hygienic Chemistry

• Kimura T

  Department Of Hygienic Chemistry Faculty Of Pharmaceutical Sciences Hokuriku University

• 景山 節

  京都大学霊長類研究所人類進化モデル研究センター

• 景山 節

  京大・霊長研

• Ho Ing

  ミシシッピ大学医学部薬毒理学教室

• Watanabe Kazuhito

  Department Of Hygienic Chemistry Faculty Of Pharmaceutical Sciences Hokuriku University

• Kimura T

  Department Of Medicinal Chemistry Center For Frontier Research In Medicinal Science 21st Century Coe

• Kimura Toshiyuki

  Faculty Of Engineering Yokohama National University

• Kondo S

  Kyoritsu Coll. Pharmacy Tokyo Jpn

• Tateoka Yuji

  Department Of Hygienic Chemistry Faculty Of Pharmaceutical Sciences Hokuriku University

• Turski Krzysztof

  Institute Of Basic Sciences Military School Of Medicine

• Watanabe Kazuhito

  Faculty Of Pharmaceutical Sciences Hokuriku University

• Yamamoto I

  Hygienic Chemistry

• Watanabe Kazuhito

  Faculty Of Pharmaceutical Sciences Kyushu University

• Yamamoto Ikuo

  Faculty Of Education Yokohama National University

• Draminski Marcin

  Institute Of Basic Sciences Military School Of Medicine:(present Address)the Ludwik Rydygier Medical

• Kimura T

  Peptide Inst. Inc. Minoh Jpn

関連論文

• Effect of annealing on DLC characteristics by ESR spectral analysis
• ペプシノーゲンの活性科機構(生理学)
• ニホンツキノワグマのペプシノーゲンとペプシンの精製および霊長類との比較検討(生化学)
• ペプシノーゲンの活性化ペプチドの一次構造にもとづく霊長類の系統-II. : ヒトとニホンザルの分岐(分類・系統学)
• カンナビノイドの代謝的活性化とシトクロムP450分子種
• Butyrylcholinesterase and Erythrocyte Sulfhydryl-dependent Enzyme Hydrolyze Gabexate in Human Blood
• Involvement of Human Blood Arylesterases and Liver Microsomal Carboxylesterases in Nafamostat Hydrolysis
• サル腎ミクロソームによるTetrahydrocannabinolの代謝
• Brillouin Scattering Study of the Volume Phase Transition in Poly-N-Isopropylacrylamide Gels
• サル肝ミクロソーム酵素によるレチナールからレチノイン酸への代謝
• CYP2C29に高い相同性を有するサル肝ミクロソーム中のP450精製とその性質
• Hepatic Metabolism of Methyl Anthranilate and Methyl N-Methylanthranilate as Food Flavoring Agents in Relation to Allergenicity in the Guinea Pig
• Stereospecific and Regioselective Hydrolysis of Cannabinoid Esters by ES46.5K, an Esterase from Mouse Hepatic Microsomes, and Its Differences from Carboxylesterases of Rabbit and Porcine Liver(Biochemistry)
• In Vitro Inhibitory Effects of Cannabinoids on Progesterone 17α-Hydroxylase Activity in Rat Testis Microsomes
• Synthesis of N^3-Substituted Uridine and Related Pyrimidine Nucleosides and Their Antinociceptive Effects in Mice
• Major Cytochrome P450 Enzymes Responsible for Microsomal Aldehyde Oxygenation of 11-Oxo-〓^8-tetrahydrocannabinol and 9-Anthraldehyde in Human Liver
• Skin Reaction Induced by Aldehydes for Food Flavoring Agents
• Possible Existence of a Novel Receptor for Uridine Analogues in the Central Nervous System Using Two Isomers, N^3-(S)-(+)-and N^3-(R)-(-)-α-Hydroxy-β-phenethyluridines
• Hypnotic Action of N^3-Substituted Arabinofuranosyluracils on Mice
• Cross-Reactivity of Various Tetrahydrocannabinol Metabolites with a Monoclonal Antibody against Tetrahydrocannabinolic Acid
• A Carbonyl Reductase-Catalyzing Reduction of N^3-Phenacyluridine in Rabbit Liver
• Synthesis and Pharmacological Evaluation in Mice of Halogenated Cannabidiol Derivatives.
• Characterization of Microsomal Alcohol Oxygenase Catalyzing the Oxidation of 7-Hydroxy-Δ^8-tetrahydrocannabinol to 7-Oxo-Δ^8-tetrahydrocannabinol in Rat Liver
• Synthesis and Central Nervous System Depressant Effects of N^3-Substituted 2', 3'-O-Isopropylideneuridines
• Synthesis and Pharmacological Evaluation in Mice of Halogenated Cannabidiol Derivatives
• Pharmacologica Efects in Mice of Anandamide and Its Related Fatty Acid Ethanolamides, and Enhancement of Cataleptogenic Effect of Anandamide by Phenylmethylsulfonyl Fluoride
• Effects of Heavy Oil from the Nakhodka on Hepatic and Pulmonary Enzymes of Mice(PROCEEDINGS OF 24TH SYMPOSIUM ON TOXICOLOGY AND ENVIRONMENTAL HEALTH)
• Synthesis and Pharmacological Activities in Mice of Halogenated Δ^9-Tetrahydrocannabinol Derivatives
• Synthesis and Sedative-Hypnotic Effects of N^3-Allyl-and N^1-Allyl-5,6-substituted 2-Thiouracil Derivatives in Mice
• Defective Myosin Genes in Mutant Mice and Human Diseases
• カテプシンD, Eの切断特異性とインヴァリアント鎖のプロセシング
• 砂糖ラジカル測定による東海村臨界事故の放射線被曝の推定
• カイコ卵の Malic enzyme : その精製と性質(生化学)
• カイコ卵の酸性フォスファターゼ(生化学)
• Effective NADH-Dependent Oxidation of 7β-Hydroxy-Δ^8-tetrahydrocannabinol to the Corresponding Ketone by Japanese Monkey Hepatic Microsomes(Toxicology)
• Monkey Hepatic Microsomal Alcohol Oxygenase: Purification and Characterization of a Cytochrome P450 Enzyme Catalyzing the Stereoselective Oxidation of 7α-and 7β-Hydroxy-Δ^8-tetrahydrocannabinol to 7-Oxo-Δ^8-tetrahydrocannabinol
• A Cytochrome P450 Enzyme Responsible for the Carbon Monoxide Formation by Cannabidiol in Mouse Hepatic Microsomes.
• Inhibition of Mouse Hepatic Glutathione S-Transferase by Δ^8-Tetrahydrocannabinol p-Quinone and Cannabidiol Hydroxy-quinone.
• Microsomal Aldehyde Oxygenase (MALDO) for Tolualdehydes, Active Metabolites of Xylenes, in the Mouse Liver and Lung
• "B-4 Hydrolysis of Xenobiotics by ES46.5K, a Novel Esterase from Mouse Liver Microsomes
• Stereoselectivity in Bunitrolol 4-Hydroxylation in Liver Microsomes from Marmosets and Japanese Monkeys
• Microsomal Aldehyde Oxygenase (MALDO): Purification and Characterization of a Cytochrome P450 Isozyme Responsible for Oxidation of 9-Anthraldehyed to 9-Anthracenecarboxylic Acid in Monkey Liver
• Mechanism of Inhibitory Effects of Cannabidiol and Cannabidiol Hydroxy-quinone on the Hepatic Microsomal Drug-Metabolizing Enzymes in Mice (Proceedings of the 23rd Symposium on Toxicology and Environmental Health)
• Involvement of a Novel Mouse Hepatic Microsomal Esterase, ES46.5K, in the Hydrolysis of Phthalate Esters
• Mechanism of Hepatic Microsomal Oxidation of 11-Hydroxy-Δ^8-tetra-hydrocannabinol to 11-Oxo-Δ^8-tetrahydrocannabinol. Evidence for Hydration of the Aldehyde Formed
• Inhibitory Effect of Cannabidiol Hydroxy-quinone, and Oxidative Product of Cannabidiol, on the Hepatic Microsomal Drug-Metabolizing Enzymes of Mice
• INTERACTION OF CANNABINOIDS WITH HEPATIC MICROSOMAL DRUG-METABOLIZING ENZYME SYSTEM IN THE RAT
• Plasma surface modification of polymer substrate for cell adhesion control
• Activity evaluation of antibody immobilized onto the self-assembled phospholipid layer fabricated by plasma-assisted method
• Immobilization of bioactive molecule onto polymer surface functionalized by plasma techniques and its application to cell culture
• Plasma-assisted fabrication of self-assembled phospholipid layer onto polymer surface and its characterization
• Plasma-Assisted Immobilization of Heparin onto Low-Density Polyethylene Surface
• 4. プラズマ製薬(医療バイオ分野へのプラズマ応用)
• Conventional Synthesis of Amphiphilic Block Copolymer Utilized for Polymeric Micelle by Mechanochemical Solid-State Polymerization
• プラズマ技法による乾式DDS開発
• Preparation of Floating Drug Delivery System by Plasma Technique
• Immobilization of Antithrombotic Biomolecules on LDPE Surface Functionalized by Plasma Techniques
• Synthesis of DNA Conjugate by Mechanochemical Solid-State Polymerization and Its Affinity Separation of Oligonucleotides Having Single-Base Difference by Capillary Electrophoresis
• 病院・薬局処方で粉砕される市販錠剤からのラジカルの生成
• Mechanochemical Solid-State Polymerization (XI) : Effect of Water-Insoluble Pharmaceutical Aids on Drug Release from Mechanically Synthesized Polymeric Prodrugs
• Novel and Simple Preparation Method of Matrix-Type Composite Particles for Controlled Drug Release by Mechanical Action
• Nature of Mechanoradical Formation of Substituted Celluloses as Studied by Electron Spin Resonance
• ステンレス製容器を用いたメカノケミカル固相反応によるリボフラビンラジカルの生成
• 「日向天照水」の分析と評価
• Peroxy Radical Formation from Plasma-induced Surface Radicals of Polyethylene as Studied by Electron Spin Resonance.
• Plasma-induced Surface Radicals of Low Density Polyethylene(LDPE) Studied by Electron Spin Resonance.
• Nature of Auto-oxidations on Plasma-induced Surface Radicals of Aromatic Ring-containing Polymers as Studied by Electron Spin Resonance.
• Nature of Auto-oxidations on Plasma-induced Surface Radicals of Polyethylene Studied by Electron Spin Resonance.
• Plasma-induced Surface Radicals of Low Density Polyethylene Studied by Electron Spin Resonance.
• Special Features of Peroxy Radicals on Plasma-Irradiated Polymers.
• Compertitive Inhibition of Δ^8-Tetrahydrocannabinol and Its Active Metabolites for Cannabinoid Receptor Binding
• Anandamide, an Endogenous Cannabinoid Receptor Ligand, Also Interacts with 5-Hydroxytryptamine (5-HT) Receptor
• ペプシノ-ゲン酵素群の構造と発達過程における発現機構
• 昆虫の休眠と糖代謝
• ヒメシロモンドクガ休眠・非休眠卵の比較(内分泌・遺伝)
• カイコ卵のリンゴ酸脱水素酵素(生化学)
• カイコの休眠初期におけるグリコーゲンの代謝経路(発生)
• 類人猿におけるペプシノゲン遺伝子の多様性
• 霊長類における胃内タンパク消化酵素ペプシノゲンの多様化
• New World Monkey Pepsinogens A and C, and Prochymosins. Purification, characterization of Enzymatic Properties, cDNA Cloning, and Molecular Evolution
• カテプシンEの構造と機能--プロセシング酵素としての可能性
• Molecular Characterization of Two Monkey Dihydrodiol Dehydrogenases
• プラズマ照射した医薬品助剤を利用する新規なドラッグデリバリーシステムの開発 : 第10報 スチレン-(無水)マレイン酸共重合体を外層高分子とした二重錠剤へのプラズマ照射によるテオフィリンの放出制御
• プラズマ技術を用いる新規DDSの開発 (特集 健康の維持と増進を科学する--疫病を克服し、もっと健康に)
• Central Nervous System Depressant Effects of N^3-Substituted Derivatives of Deoxyuridine in Mice
• Preparation of Floating Drug Delivery System by Pulsed-Plasma Techniques
• Gastric digestive proteinases of the greater horseshoe bat, Rhinolophus ferrumequinum
• Pepsinogens and Pepsins from House Musk Shrew, Suncus murinus: Purification, Characterization, Determination of the Amino-Acid Sequences of the Activation Segments, and Analysis of Proteolytic Specificities^1
• Plasma-Assisted Immobilization of Bio-Molecules on LDPE Surface
• Synthesis of Water-Soluble Polymeric Prodrugs Possessing 4-Methylcatechol Derivatives by Mechanochemical Solid-State Copolymerization and Nature of Drug Release
• Introduction of Durable Hydrophilicity on Nylon12 by Plasma Treatment.
• Is the Cannabinoid CB1 Receptor a 2-Arachidonoylglycerol Receptor? Structural Requirements for Triggering a Ca^ Transient in NG108-15 Cells
• Mechanism of Pulmonary Cytochrome P450 Inactivation by Tolualdehydes, Active Metabolites of Xylenes (Proceedings of the 22nd Symposium on Toxicology and Environmental Health)
• Metabolic Reaction of Tolualdehydes by Microsomal Aldehyde Oxygenase (MALDO) in Lung (Proceedings of the 19th Symposium on Toxicology and Environmental Health)
• Histidine-Related Dipeptides, Carnosine, Anserine and Homocarnosine, Possess the CNS Depressant Effects on Mice and their Action Mechanism
• INTERACTIONS OF ACTIVE CANNABINOID METABOLITES WITH GABA_A RECEPTOR
• INHIBITION OF ANANDAMIDE AMIDASE ACTIVITY IN MOUSE BRAIN MICROSOMES BY CANNABINOIDS
• Involvement of a Novel Mouse Hepatic Esterase (ES46.5K) in the Hydrolysis of Phthalate Esters (Proceedings of the 21st Symposium on Toxicology and Environmental Health)
• Involvement of Microsomal Aldehyde Oxygenase (MALDO) in the Metabolism of Aliphatic Aldehydes in the Mouse Liver (Proceedings of the 20th Symposium on Toxicology and Environmental Health)
• Size-Dependent Hysteresis of Phase Transition in Polymer Gel

もっと見る 閉じる

スポンサーリンク