Stereospecific Taurine Conjugation of the trans-OH Metabolite (Active Metabolite) of CS-670,a New 2-Arylpropionic Acid Nonsteroidal Anti-inflammatory Drug, in Dogs
スポンサーリンク
概要
- 論文の詳細を見る
CS-670,(±)-2-[4-(2-oxocyclohexylidenemethyl) phenyl] propionic acid, is a novel derivative of 2-arylpropionic acid non-steroidal anti-inflammatory drugs (profen NSAIDs). The major urinary metabolite of this drug from dogs was isolated and its chemical structure was determined by MS and NMR spectroscopy. The metabolite was identified as a taurine conjugate of the trans-OH form (trans-OH-taurine) which was first generated by stereoselective reduction of the double bond and the carbonyl function of the CS-670 molecule. The taurine conjugate was excreted in urine as the main metabolite, regardless of the optical configuration of CS-670 administered [(2R)-enantiomer : 47.2% of the dose, (2S)-enantiomer : 70.9% of the dose]. The trans-OH-taurine was hydrolyzed by refluxing it in 6N HCl without racemization. The released trans-OH was derivatized to diastereoamides with (+)-(R)-1-(1-naphthyl) ethylamine to examine the stereochemical properties of the 2-arylpropionic acid side chain. It was found that the configuration of the 2-carbon of the trans-OH-taurine was almost entirely (S). As the CoA thioesters are obligate intermediates for amino acid conjugation, the results suggest that the (2S)-enantiomer of the trans-OH metabolite serves as a substrate for canine acyl CoA ligase (EC 6.2.1.3) as well as the (2R)-enantiomer, but only the CoA thioester with a (2S)-configuration is a substrate for taurine N-acyl transferase. It is interesting to note that these results are not consistent with the chiral inversion mechanism by which the (2R)-enantiomers of profen NSAIDs are stereospecifically converted to CoA thioester intermediates.
- 社団法人日本薬学会の論文
- 1995-11-15
著者
-
高崎 渉
Analytical and Metabolic Research Laboratories, Sankyo Co., Ltd.,
-
春山 英幸
Analytical and Metabolic Research Laboratories
-
田中 頼久
東北薬科大・第一薬剤学
-
高崎 渉
三共・薬剤動態研
-
岩渕 晴男
三共(株)薬剤動態研究所
-
高崎 渉
Analytical And Metabolic Research Laboratories Sankyo Co. Ltd.
-
浅見 正人
三共株式会社 分析代謝研究所
-
浅見 正人
Analytical and Metabolic Research Laboratories Sankyo Co.
-
岩渕 晴男
Analytical and Metabolic Research Laboratories Sankyo Co.
-
和智 一之
Medicinal Chemistry Research Laboratories, Sankyo Co.
-
寺田 敦祐
Medicinal Chemistry Research Laboratories, Sankyo Co.
-
田中 頼久
Analytical and Metabolic Research Laboratories Sankyo Co.
-
和智 一之
京都薬科大学 化学研究所
-
寺田 敦祐
京都薬科大学 化学研究所
-
春山 英幸
三共株式会社薬物動態研究所
-
Haruyama Hideyuki
Analytical And Metabollic Research Laboratories
-
Terada A
Medicinal Chemistry Research Laboratories Sankyo Co. Ltd.
関連論文
- 抗糖尿病薬トログリタゾンの新規キノンエポキシド代謝物の同定と細胞障害性
- FEASIBILITY OF USING [^O_2]11-DEHYDROTHROMBOXANE B_2 AS AN INTERNAL STANDARD OF IMMUNOAFFINITY PURIFICATION FOLLOWED BY GAS CHROMATOGRAPHY/SELECTED ION MONITORING
- 腎移植患者におけるシクロスポリンAの血中動態におよぼす糖尿病の影響
- Structure Elucidation of the Bioactive Metabolites of ML-236B (Mevastatin) Isolated from Dog Urine
- サルにおける抗糖尿病薬Troglitazoneの体内動態
- ラット及びヒト肝上清アセトイン還元酵素の解析
- トログリタゾンによる肝障害の機序解明への薬物動態学的アプローチ - UGTの多型は肝障害の要因となり得るか? -
- 168 気管支喘息患者における末梢血好酸球活性化の各評価法による検討
- 抗痙縮剤CS-722の代謝研究 - ラットにおける主要代謝物とモルフォリン環の代謝を中心 -
- 糖尿病モデルラットにおけるシクロスポリンAの腸管吸収
- 糖尿病モデルラットにおけるプレドニゾロンのステロイド脱水素酵素による代謝について
- テオフィリン徐放性製剤の溶出性に及ぼす牛乳の影響
- P-149 テオフィリン徐放錠の溶出性に及ぼす嚥下補助ゼリーの影響
- 25-P6-34 テオフィリン徐放性製剤の服用方法に関する研究
- 新規抗血小薬CS-747の代謝活性化機構
- 血液脳関門におけるヒスチジンとそのアナログの輸送に及ぼす亜鉛の効果
- A型MAO阻害剤RS-8359のキラルインバージョン
- Studies on Acetylenic Compounds. XLIII. Synthesis of Ibotenic Acid.
- Studies on Acetylenic Compounds. XLIII. Synthesis of Ibotenic Acid
- HMG-CoA還元酵素阻害剤の薬物代謝酵素阻害作用
- 新規抗うつ薬RS-8359のラットおよびイヌ尿中代謝物の構造決定
- 新規2-アリルプロピオン酸系非ステロイド抗炎症薬CS-670の体内動態(1):マウス, ラットおよびイヌにおける吸収, 代謝ならびに排泄
- Stereospecific Taurine Conjugation of the trans-OH Metabolite (Active Metabolite) of CS-670,a New 2-Arylpropionic Acid Nonsteroidal Anti-inflammatory Drug, in Dogs
- プロフェン系抗炎症薬CS-670のイヌにおける立体特異的タウリン抱合
- Studies on 1,3-Benzoxazines. III. Reaction of Imidoyl Chlorides of 1,3-Benzoxazines with 2-Hydroxy- or 2-Mercaptopyridine N-Oxides : A Novel S-N Bond Formation via Electrocyclic Rearrangement
- Purification and Some Properties of Ketone Reductase Forming an Active Metabolite of Sodium 2-[4-(2-Oxocyclopentylmethyl)-phenyl] propionate Dihydrate (Loxoprofen Sodium), a New Anti-inflammatory Agent, in Rabbit Liver Cytosol
- Structural Determination of Rat Urinary Metabolites of Sodium 2-[4-(2-Oxocyclopentylmethyl) phenyl] propionate Dihydrate (Loxoprofen Sodium), a New Anti-inflammatory Agent
- Optical Inversion of (2R)-to (2S)-Isomers of 2-[4-(2-Oxocyclopentylmethyl)-phenyl] propionic Acid (Loxoprofen), a New Anti-inflammatory Agent, and Its Monohydroxy Metabolites in the Rat
- Determination of Configurations of the Two DL-Isomers of 1-(p-Nitrophenyl)-3-(2,2-dichloroacetamido)-1,2-propanediols.
- Syntheses of 1-(p-Nitrophenyl)-3-(2,2-dichloroacetamido)-1,2-propanediols.
- A Quantitative Analysis of Proton Nuclear Magnetic Relaxation : Conformation Analysis of Substituted 5,1-Benzothiazocine and Its Homologue(Organic,Chemical)
- 古くて新しい薬ニトログリセリンの耐性機構は未だ不明
- A型MAO阻害剤RS-8359の立体選択的水酸化
- Studies on Acetylenic Compounds. LIII. The Reactions of Acetylenic Sulfonium Salts with Acid Anhydride or Acid Chloride
- Studies on Acetylenic Compounds. LII. Reactions of Acetylenic Sulfonium Salts with Cyclohexanone and Cyclopentanone
- Rearrangements and Reactions of Stable Sulfonium Ylids from Acetylenic Sulfonium Salts
- Studies on Acetylenic Compounds. LI. The Reactions of Acetylenic Sulfonium Salts with Benzaldehyde
- Studies on 1,3-Benzoxazines. VII. Formation of Diphenylpyrimidines by the Reaction of 4-Chloro-2H-1,3-benzoxazines with Ethyl 3-Aminobutyrate
- Studies on 1,3-Benzoxazines. VI. Formation of Quinazolines and 4H-3,1-Benzoxazines by the Reaction of 4-Chloro-2H-1,3-benzoxazines with Aminoacetophenone, Aminobenzophenone and Aminobenzyl Alcohol Derivatives
- Reactions of 2-Piperidylacetohydrazides with Ethyl Acetoacetate or Acetylenic Acid Esters. Formation of 3,4-Dimethylpyrano-[2,3-c] pyrazol (6) ones and Perhydropyrazolo [2,3-a]-pyrido [1,2-c] pyrimidin-2,5-diones
- Studies on Benzodiazepinooxazoles. V. Reactions of Benzo [6,7]-1,4-diazepino [5,4-b] oxazole Derivatives with Acetic Anhydride
- Studies on Benzodiazepinooxazoles. IV. The Formation of Quinolones by the Ring Contraction of a Benzo [6,7]-1,4-diazepino [5,4-b]-oxazole Derivative
- Studies on Benzodiazepinooxazoles. III. Reactions and Rearrangements of Benzo [6,7]-1,4-diazepino-[5,4-b] oxazole Derivatives
- Sensitivity of Steroid Enzyme Immunoassays. : Use of 3,3', 5,5'-Tetramethylbenzidine as a Chromogen in the Assay System with Glucose Oxidase Label
- Enzyme Labeling of Steroids by the N-Succinimidyl Ester Method. Preparation of Glucose Oxidase-Labeled Antigen for Use in Enzyme Immunoassay(Analytical,Chemical)
- A Comparison of Chromogenic Substrates for Horseradish Peroxidase as a Label in Steroid Enzyme Immunoassay
- Enzyme Labeling of Steroids by the N-Succinimidyl Ester Method. Preparation of Alkaline Phosphatase-Labeled Antigen for Use in Enzyme Immunoassay
- Chemical Conversion of Corticosteroids to 3α, 5α-Tetrahydro Derivatives. Synthesis of Allotetrahydro-11-deoxycortisol Glucuronides
- Proton Nuclear Magnetic Relaxation : An Application to the Study of the Conformation and Configuration of Saframycin A
- ラットmonoamine oxidase mRNAの臓器分布と活性値との相関関係
- 自然発症糖尿病ラット(GKラット)に対する桑葉の抗糖尿病作用
- 高コレステロール摂食ラットの血清,肝臓及びリポタンパク中の脂質濃度に及ぼすセレンの影響
- A Quantitative Analysis of Nuclear Magnetic Relaxation : The Configuration and the Conformation of ML-236B(Mevastatin) Metabolites(Organic,Chemical)
- Optical Resolution of (±)-2-[4-(2-Oxocyclohexylidenemethyl)phenyl]propionic Acid
- Synthesis of the Eight Possible Optically Active Isomers of 2-[4-(2-Hydroxycyclopentylmethyl) phenyl] propionic Acid
- Optical Resolution and Determination of Absolute Configuration of (±)-2-[4-(2-Oxocyclopentylmethyl) phenyl] propionic Acids
- Studies on 1,3-Benzoxazines. II. New Rearrangement Modes in the Reaction of 4-Chloro-2,2-dimethyl-2H-1,3-benzoxazine with Substituted Pyridine N-Oxides
- Formation of Triazole and Isoxazole Derivatives from β-Substituted Pyridinium Salts
- Formation of Pyrazole Derivatives from β-Substituted Pyridinium Salts
- Studies on 1,3-Benzoxazines. I. Synthesis of Primary 2-Aminopyridines via the Reaction of Imidoyl Chlorides of 1,3-Benzoxazines with Pyridine N-Oxides
- Opitical Resolution and Determination of Absolute Configuration of 2-(2-Isopropylindan-5-yl) propionic Acid
- Bischler-Napieralski Reactions of N-(2-Indolylethyl) acetamide
- 2型糖尿病モデル動物Goto-Kakizakiラットにおける11β-Hydroxysteroid Dehydrogenaseの変動〜肝臓における上昇および脂肪組織における低下〜
- ラット脂肪細胞へのグルコース輸送に対するセレンの効果
- アルデヒドオキシターゼの薬物代謝酵素学的諸性質
- Studies on Acetylenic Compounds. L. The Formation of Stable Sulfonium Ylids from Acetylenic Sulfonium Salts
- The Reactions of Ethyl cis-β-Chloroacrylate with Aminomalonate Derivatives
- Studies on Acetylenic Compounds. XLVIII. The Reactions of Allenic and Acetylenic Sulfides with Methyl Iodide
- Studies on Acetylenic Compounds. XLVII. The Rearrangement of Acetylenic Sulfonium Salts
- Studies on Acetylenic Compounds. XLVI. The Reactions of Acetylenic Compounds with Thiourea or Ammonium Dithiocarbamate