Structure-Activity Relationships of Receptor Binding of 1,4-Dihydropyridine Derivatives(Pharmacology)

スポンサーリンク

概要

• 論文の詳細を見る

• The present study was undertaken to investigate binding activity of synthesized 1,4-dihydropyridine (1,4-DHP) derivatives (Compounds 1-124) to 1,4-DHP calcium channel antagonist receptors in rat brain. Sixteen 1,4-DHP derivatives inhibited specific (+)-[^3H]PN 200-110 binding in rat brain in a concentration-dependent manner with IC_<50> value of 0.43 to 3.49 μM. Scatchard analysis revealed that compounds 54, 69, 85, like nifedipine, caused a significant increase in apparent dissociation constant (K_d) for (+)-[^3H]PN 200-110, while compounds 68, 69 and 80 caused a significant decrease in maximal number of bindings sites (B_<max>). These data suggest that compounds 68, 69 and 80 exert longer-acting antagonistic effects of 1,4-DHP receptors than compounds 54, 69 and 85. The structure-activity relationship study has revealed that 1) ester groups in 3- and 5-positions are the most effective, 2) the aryl group in the 4-position of 1,4-DHP ring is the basic requirement for optimal activity, 3) position and type of electron-withdrawing groups on phenyl group at position 4 would affect the receptor-binding activity. Furthermore, compound 58 exerted al receptor binding activity, being 1.6 times greater than 1,4-DHP receptors. Compounds 81, 84, 91, 94, 106, 108 and 109 showed significant binding of ATP-sensitive potassium (K_<ATP>) channel, and the binding activities of compounds 81, 84, 108 and 109 were 1.6-3.8 times greater than the binding activity for 1,4-DHP receptors. Compounds 91 and 106 had similar binding activity for K_<ATP> channel and 1,4-DHP receptors. In conclusion, the present study has shown that novel 1,4-DHP derivatives exert relatively high binding affinity to 1,4-DHP receptors and has revealed new aspect of structure-activity relationships of 1,4-DHP derivatives, especially hexahydroquinoline derivatives.

• 社団法人日本薬学会の論文
• 2008-03-01

著者

• Ito Yoshihiko

  Department of Molecular Science and Technology, Doshisha University

• 山田 幸子

  日本大学医学部生化学分野

• 山田 愼一

  トーアエイヨー株式会社

• Oyunzul Luvsandorj

  Department Of Pharmacokinetics And Pharmacodynamics And Global Center Of Excellence (coe) Program Sc

• Oyunzul Luvsandorj

  静岡県立大学 グローバルcoeプログラム

• YAMADA Shizuo

  Department of Pharmacokinetics and Pharmacodynamics and Global Center of Excellence (COE) Program, S

• Yamada Shizuo

  Departments Of Pharmacokinetics And Pharmacodynamics Pharmacognosy And Global Center Of Excellence (

• TAKAHASHI Daiki

  Department of Pharmacokinetics and Pharmacodynamics and Global COE Program, School of Pharmaceutical

• ONOUE Satomi

  Department of Pharmacokinetics and Pharmacodynamics and Global COE Program, School of Pharmaceutical

• UCHIDA Shinya

  Department of Pharmacokinetics and Pharmacodynamics and Global COE Program, School of Pharmaceutical

• SIMSEK Rahime

  Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Hacettepe University

• GUNDUZ Miyase

  Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Hacettepe University

• SAFAK Chiat

  Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Hacettepe University

• Safak Chiat

  Department Of Pharmaceutical Chemistry Faculty Of Pharmacy Hacettepe University

• Onoue Satomi

  Departments Of Pharmacokinetics And Pharmacodynamics Pharmacognosy And Global Center Of Excellence (

• Gunduz Miyase

  Department Of Pharmaceutical Chemistry Faculty Of Pharmacy Hacettepe University

• Uchida S

  Department Of Hospital Pharmacy Hamamatsu University School Of Medicine

• Uchida Shinya

  Department Of Biopharmacy School Of Pharmaceutical Sciences University Of Shizuoka

• Simsek Rahime

  Department Of Pharmaceutical Chemistry Faculty Of Pharmacy Hacettepe University

• Uchida Shinya

  Department Of Hospital Pharmacy Hamamatsu University School Of Medicine

• Onoue Satomi

  Department Of Analytical Chemistry Faculty Of Pharmaceutical Sciences Toho University

• Yamada S

  School Of Pharmaceutical Sciences And Coe21 University Of Shizuoka

• Yamada Shizuo

  Department Of Pharmacokinetics And Pharmacodynamics And Global Center Of Excellence (coe) And Clinic

• Yamada S

  Department Of Biopharmacy University Of Shizuoka School Of Pharmaceutical Sciences

• Uchida Shinya

  Department Of Pharmacokinetics And Pharmacodynamics And Global Coe Program School Of Pharmaceuticals

• Uchida Shinya

  Department Of Pharmacokinetics And Pharmacodynamics And Global Coe Program School Of Pharmaceutical

• Ito Yoshihiko

  Dep. Of Pharmacokinetics And Pharmacodynamics And Global Center Of Excellence (coe) Program School O

• Yamada Shizuo

  Department Of Pharmacokinetics And Pharmacodynamics And Global Coe Program School Of Pharmaceutical

• Yamada Shizuo

  Department Of Biophamacy School Of Pharmaceutical Sciences University Of Shizuoka

• Ito Yoshihiko

  Department Of Mathematics Faculty Of Education Kumamoto University

• Takahashi Daiki

  Department Of Pharmacokinetics And Pharmacodynamics And Global Coe Program School Of Pharmaceuticals

• Uchida Shinya

  Department Of Anesthesiology Gunma University Hospital

• Oyunzui Luvsandorj

  Department of Pharmacokinetics and Pharmacodynamics and Global COE Program, School of PharmaceuticalSciences, University of Shizuoka

• Oyunzui Luvsandorj

  Department of Pharmacokinetics and Pharmacodynamics and Global Center of Excellence (COE) Program, School of Pharmaceutical Sciences, University of Shizuoka

関連論文

• Palladium-catalyzed 1,2-addition of alkylborane reagents to aldehydes
• 2-I-13 リガンド選択的なビタミンD受容体作用発現機構の解析(一般演題,日本ビタミン学会第62回大会発表要旨)
• リトコール酸誘導体は高カルシウム血症を伴わない作用選択的ビタミンD受容体アゴニストである(研究論文紹介)
• 2-I-17 リガンドを介した1α,25(OH)_2D_3/VDRのアロステリックコミュニケーション(一般演題,日本ビタミン学会第62回大会発表要旨)
• Pharmacologically Relevant Receptor Binding Characteristics and 5α-Reductase Inhibitory Activity of Free Fatty Acids Contained in Saw Palmetto Extract(Pharmacology)
• 4. ビタミンD受容体のリガンド選択的作用発現機構の解析(第319回会議研究発表要旨,脂溶性ビタミン総合研究委員会)
• Effects of Dietary Ingredients on Function and Expression of P-Glycoprotein in Human Intestinal Epithelial Cells
• 4.ビタミンD受容体に作用する胆汁酸誘導体(脂溶性ビタミン総合研究委員会 第305回会議研究発表要旨)
• 1-I-2 微生物によるビタミンD_3およびその誘導体の水酸化反応生成物
• 6.ビタミンD受容体タンパク質複合体のリガンド選択的ダイナミック相互作用(第327回会議研究発表要旨,脂溶性ビタミン総合研究委員会)
• 2-C-7 ビタミンD_31α位水酸化酵素CYP27B1の酵素学的性質の解明(第57回大会一般研究発表)(第57回大会研究発表要旨)
• 2-IV-23 マウス由来ビタミンD_31α位水酸化酵素CYP27B1の構造と機能の解析(第56回大会一般研究発表)
• ビタミンD水酸化酵素(CYP27B1,CYP27A1)のホモジーモデリング : 三次元構造と機能
• ビタミンD-1α-水酸化酵素の三次元構造と機能発現
• リトコール酸誘導体は高カルシウム血症を伴わない作用選択的ビタミンD受容体アゴニストである
• Langmuir-Blodgett films of helical rigid-rod poly(quinoxaline-2,3-diyl)s
• 1-IV-3 ビタミンD受容体にpassive antagonistとして機能するリガンドの構造活性相関(ビタミン学の原点・栄養学への21世紀的回帰, 日本ビタミン学会第59回大会)
• 4.アダマンチルビタミンD誘導体を結合したビタミンD受容体の結晶構造 : ビタミンD受容体アンタゴニズム/パーシャルアゴニズムの分子基盤(第321回会議研究発表要旨,脂溶性ビタミン総合研究委員会)
• 2. 変異ビタミンD受容体(R274L VDR)の選択的アゴニストの創製(第314回会議研究発表要旨,脂溶性ビタミン総合研究委員会)
• 2.新規,高活性ビタミンDアンタゴニスト : 26-Adamantyl-25-hydroxyl-2-methylene-19-norvitamin D誘導体(第313回会議研究発表要旨,脂溶性ビタミン総合研究委員会)
• 2.ビタミンD受容体 : リトコール酸誘導体複合体の結晶構造解析(第312回会議研究発表要旨,脂溶性ビタミン総合研究委員会)
• 2-I-20 ビタミンDの活性発現を制御する新規誘導体の合成と構造活性相関(一般研究発表,日本ビタミン学会 第58回大会研究発表要旨)
• 1. 脂溶性ビタミン総合研究委員会との関わり(脂溶性ビタミン総合研究委員会第307回会議研究発表要旨)
• 2-C-9 ビタミンD受容体のアロステリックネットワーク(第57回大会一般研究発表)(第57回大会研究発表要旨)
• 2-C-2 22位にイオウ原子を含む2-置換19-ノルビタミンD誘導体の合成と生物活性(第57回大会一般研究発表)(第57回大会研究発表要旨)
• 1.PPARγ活性をもつ4-置換-ドコサヘキサエン酸誘導体の設計と合成および抗糖尿病活性(脂溶性ビタミン総合研究委員会第306回会議研究発表要旨)
• PPARγ活性をもつ高度不飽和脂肪酸誘導体の設計と合成および抗糖尿病活性 (生体機能と創薬シンポジウム2005--疾病に関わる生体分子と治療薬) -- (シンポジウム2 代謝性疾患克服を目指した核内受容体リガンドの創製)
• 2-IV-25 ビタミンD_324位水酸化酵素CYP24の構造と機能の解析(第56回大会一般研究発表)
• 2-IV-22 ビタミンD受容体のアラニンスキャニング変異解析(第56回大会一般研究発表)
• 2-IV-20 側鎖を修飾した新規2-置換19-ノルビタミンDアナログの合成(第56回大会一般研究発表)
• 2. VDR-LBPに面している全アミノ酸残基の役割 : Complete Alanine Scanning Mutational Analysis(第301回脂溶性ビタミン総合研究委員会研究発表要旨)
• ビタミンDと受容体:相互作用の網羅的解析
• 2-I-20新規2,2-ジ置換-19-ノルビタミンDアナログの合成と生物活性(第55回大会一般研究発表)
• Fluorinated Vitamin D Analogs to Probe the Conformation of Vitamin D in Its Receptor Complex : ^F-NMR Studies and Biological Activity
• 19-ノルビタミンDアナログを基盤としたA環構造と活性相関
• 13 ビタミンDレセプターのリガンド認識、有機化学的アプローチ(口頭発表の部)
• 2.グルコースをビルディングブロックに用いたA環部構築法を基盤とした19-ノルビタミンDアナログの合成
• 1-I-1 D-グルコースをA環部前駆体とする2-ヒドロキシ-19-ノルビタミンDアナログの合成
• (10Z)-and(10E)-19-Fluoro-1α, 25-dihydroxyvitamin D_3 : An Improved Synthesis via 19-Nor-10-oxo-vitamin D
• 計算化学と合成化学を駆使したビタミンDの三次元構造活性相関
• 2. ビタミンD受容体リガンド結合領域の構造とビタミンDの構造活性相関
• Synthesis of (10Z)- and (10E)-19-Fluoro-1α, 25-dihydroxyvitamin D_3 : Compounds to Probe Vitamin D Conformation in Receptor Complex by ^F-NMR
• ビタミンD受容体リガンド結合領域の三次元構造構築とリガンドドッキング
• 1-I-5 受容体リガンド結合ポケット内でのビタミンDの構造と相互作用
• 1-I-1 糖を用いた 2-置換-19-ノルビタミン DアナログのA環シントンの合成
• Structure-Activity Relationships of Receptor Binding of 1,4-Dihydropyridine Derivatives(Pharmacology)
• 2-[(R^*s, 9S^*)-(4-メトキシ-6,7,8,9-テトラヒドロ-5H-シクロヘプタ[b]ピリジン-9-イル)スルフィニル]-1H-ベンズイミダゾールナトリウム塩の安定な溶媒和物の合成
• Synthetic Study of 2-[(6,7,8,9-Tetrahydro-5H-cyclohepta[b]pyridin-9-yl)-sulfinyl]-1H-benzimidazole Analogs and Their Biological Properties as Novel Proton Pump Inhibitors
• 1. 核内受容体への結合とその後の作用発現におけるビタミンD立体配座の重要性
• PJ-566 Influence of CYP2C9 Genotype on Pharmacokinetics and Pharmacodynamics of Benzbromarone(Cardiovascular pharmacology, basic/clinical-6, The 71st Annual Scientific Meeting of the Japanese Circulation Society)
• Comparative Evaluation of Exocrine Muscarinic Receptor Binding Characteristics and Inhibition of Salivation of Solifenacin in Mice(Pharmacology)
• Isolation and Pharmacological Characterization of Fatty Acids from Saw Palmetto Extract
• SYNTHESIS AND ISOMERIZATION OF OPTICAL ACTIVE 2-[(6,7,8,9-TETRAHYDRO-5H-CYCLOHEPTA[b]PYRIDIN-9-YL)SULFINYL]-1H-BENZIMIDAZOLE ANALOGS
• SYNTHESES AND ANTIULCER ACTIVITIES OF NOVEL 2-[(6,7,8,9-TETRAHYDRO-5H-CYCLOHEPTA[b]PYRIDIN-9-YL)SULFINYL]-1H-BENZIMIDAZOLE ANALOGUES
• Acetylcholinesterase-Inhibitiory Activities and Brain Distribution of Novel Four Quinoline Compounds as Nootropics
• Enhancement by Grapefruit Juice of Morphine Antinociception(Pharmacology)
• ビタミンDの三次元構造活性相関
• 2-II-4 ビタミンDのVDRリガンド結合領域へのドッキング
• 2-II-3 ホモロジーモデリングに基づくビタミンD受容体リガンド結合領域の3次元構造
• 核内レセプターリガンド結合領域の立体構造とリガンド認識
• Antinociceptive Effects of St. John's Wort, Harpagophytum Procumbens Extract and Grape Seed Proanthocyanidins Extract in Mice(Pharmacology)
• 2-II-2 フッ素化ビタミンDアナログを基盤としたビタミンDのA環コンフォメーション
• 5. 4-および19-フッ素化ビタミンDアナログのA環コンフォメーション
• P-253 DEVELOPMENT OF POTENT HISTAMINE H_3 AND/OR H_4 RECEPTOR ANTAGONISTS BY THE STEREOCHEMICAL DIVERSITY-ORIENTED CONFORMATIONAL RESTRICTION STRATEGY
• Synthesis of Conformationally Restricted Analogs of Baclofen, a Potent GABA_B Receptor Agonist, by the Introduction of a Cyclopropane Ring
• Asymmetric 1,4-Addition Reaction of Arylboronic Acid to Eneone Catalyzed by Palladium with Ferrocene-based Phosphine Ligand
• Palladium Catalyzed Conjugate 1,4-Addition of Organoboronic Acids to α,β-Unsaturated Ketones
• Palladium-Catalyzed Coupling Reactions of N-Methoxy-N-methylcarbamoyl Chloride for the Synthesis of N-Methoxy-N-methylamides
• Regio-and Stereoselective Incorporation of a ^C Nuclide into D-ribo-Phytosphingosine via SmI_2-Mediated C-C Formation with ^C-Labeled Isocyanide
• Preparation of (Alkaneimidoyl)lanthanides and Their Reactions with Carbonyl Compounds
• Alkyllithium-Mediated Anomalous Trimerization of 2,6-Xylyl Isocyanide
• Reduction of α,β-Unsaturated Ketones with Diphenylsilanes Bearing Several Substituents on Their Phenyl Moiety Catalyzed by Rhodium-Phosphine Complexes
• Trans-Chelating Chiral Peralkyldiphosphine Ligands (R,R)-(S,S)-2,2''- Bis[1-(dialkylphosphino)ethyl]-1,1''-biferrocenes (AlkylTRAPs) and Their Transition Metal Complexes
• Blood-Brain Permeability of [^3H]-(3-methyl-His^2) Thyrotropin-releasing Hormone (MeTRH) in Mice : Effects of TRH and its Analogues
• In Vivo Measurement of 1, 4-Dihydropyridine Receptors in Mesenteric Arteries of Spontaneously Hypertensive Rats and Effect of Nifedipine and Cilnidipine
• Muscarinic Receptor Binding Characteristics in Rat Tissues after Oral Administration of Oxybutynin and Propiverine
• Improvement in the Histopathology of Hearts from Cardiomyopathic BIO TO-2 Hamsters Following Long-Term Administration of Amlodipine and Cilnidipine
• Ex Vivo and in Vivo α_1-Adrenoceptor Binding Characteristics of a Novel α_-Adrenoceptor Antagonist, JTH-601,in Rat Tissues
• Comparative Study on Pharmacokinetics and in Vivoα_1-Adrenoceptor Binding of [^3H]Tamsulosin and [^3H]Prazosin in Rats
• Racemization and Deracemization of Poly(quinoxaline-2,3-diyl)s
• 有機銅試薬の共役付加反応における面選択性と反応機構 : 一般則の提案
• ビタミンD_3代謝分解系の主要な反応はCYP24により触媒される
• 3.24R、25-ヒドロキシビタミンD_3のin vivo代謝と胆汁主代謝産物の構造決定 : 脂溶性ビタミン総合研究委員会第274回会議研究発表要旨
• PB33 ASYMMETRIC SYNTHESIS OF β-HYDROXYL-α-AMINO ACIDS BY ASYMMETRIC ALDOL REACTION OF α-ISOCYANOCARBOXYLATES CATALYZED BY CHIRAL FERROCENYLPHOSPHINE-GOLD (I) COMPLEXES
• PB64 INTRAMOLECULAR HYDROSILATION : A NEW STEREOCONTROLLED SYNTHETIC METHOD IN CARBOHYDRATE CHEMISTRY
• A 12-month Feeding Study of Reproduction/Development in Rats Fed Meat/Milk Powder Supplemented Diets Derived from the Progeny of Cloned Cattle Produced by Somatic Cell Nuclear Transfer
• Catalytic Asymmetric Hydrogenation of α-(Acetamido)acrylates Using TRAP Trans-Chelating Chiral Bisphosphine Ligands: Remarkable Effects of Ligand P-Substituent and Hydrogen Pressure on Enantioselectivity
• Asymmetric Hydrosilylation of Ketones Using Trans-Chelating Chiral Peralkylbisphosphine Ligands Bearing Primary Alkyl Substituents on Phosphorus Atoms
• Synthesis and Structural Analysis of Oligo(naphthalene-2, 3-diyl)s
• Stereoselective Synthesis via Palladium-Catalyzed Intramolecular Bis-Silylation
• Pharmacokinetic and Pharmacodynamic Analysis of Acetylcholinesterase Inhibition by Distigmine Bromide in Rats
• Demonstration of Muscarinic and Nicotinic Receptor Binding Activities of Distigmine to Treat Detrusor Underactivity
• Rhodium-Catalyzed Enantioselective Michael Addition of (1-Cyanoethyl)phosphonate: Synthesis of Optically Active Phosphonic Acid Derivatives with Phosphorus-Substituted Quaternary Asymmetric Carbon Center
• 1.活性型ビタミンD_3及びリトコール酸によるリガンド選択的なビタミンD受容体標的遺伝子の発現誘導(第329回会議研究発表要旨,脂溶性ビタミン総合研究委員会)
• Benzbromarone Pharmacokinetics and Pharmacodynamics in Different Cytochrome P450 2C9 Genotypes
• 蛍光性ジエノフィルDMEQ-TAD : ビタミンD代謝物の高感度蛍光アッセイ法と臨床への応用
• (2)ビタミンDの代謝研究, 活性型ビタミンDの発見 (ビタミン研究のブレークスルー : 「ビタミンD」)
• (1)ビタミンDの発見から構造決定まで (ビタミン研究のブレークスルー : 「ビタミンD」)
• 1. ビタミンDアナログの三次元構造と活性 : 立体配座制御アナログの合成と活性に関する研究を基盤にして (故小林正委員メモリアルシンポジウム)
• Effects of Short-Term Consumption of a Large Amount of Tea Catechins on Chromosomal Damage, Oxidative Stress Markers, Serum Lipid, Folic Acid, and Total Homocysteine Levels : A Randomized, Double-Blind, Controlled Study

もっと見る 閉じる

スポンサーリンク