Retinoidal Pyrimidinecarboxylic Acids. Unexpected Diaza-Substituent Effects in Retinobenzoic Acids

スポンサーリンク

概要

• 論文の詳細を見る

• Several pyridine-and pyrimidine-carboxylic acids were synthesized as ligand candidates for retinoid nuclear receptors, retinoic acid receptors (RARs) and retinoic X receptors (RXRs). Although the pyridine derivatives, 6-[(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)carbamoyl]pyridine-3-carboxylic acid (2b) and 6-[(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)carboxamido]pyridine-3-carboxylic acid (5b) are more potent than the corresponding benzoic acid-type retinoids, Am80 (2a) and Am580 (5a), the replacement of the benzene ring of Am580 (5a), Am555 (6a), or Am55 (7a) with a pyrimidine ring caused loss of the retinoidal activity both in HL-60 cell differentiation assay and in RAR transactivation assay using COS-1 cells. On the other hand, pyrimidine analogs (PA series, 10 and 11) of potent RXR agonists (retinoid synergists) with a diphenylamine skeleton (DA series, 8 and 9) exhibited potent retinoid synergistic activity in HL-60 cell differentiation assay and activated RXRs. Among the synthesized compounds, 2-[N-n-propyl-N-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)amino]pyrimidene-5-carboxylic acid (PA013,10e) is most active retinoid synergist in HL-60 assay.

• 公益社団法人日本薬学会の論文
• 2000-10-01

著者

• FUKASAWA Hiroshi

  Graduate School of Pharmaceutical Sciences, The University of Tokyo

• KAGECHIKA Hiroyuki

  Graduate School of Pharmaceutical Sciences, The University of Tokyo

• Kagechika Hiroyuki

  Graduate School Of Pharmaceutical Sciences The University Of Tokyo:research Foundation Itsuu Laborat

• Kagechika Hiroyuki

  Graduate School Of Biomedical Sci. Tokyo Medical And Dental Univ.

• Itai Akiko

  Insitute Of Medicinal Molecular Design Key Molecular Inc.

• HASHIMOTO Yuichi

  Institute of Molecular & Cellular Biosciences, The University of Tokyo

• Hashimoto Yuichi

  Univ. Tokyo Tokyo Jpn

• Hashimoto Y

  Univ. Tokyo Tokyo Jpn

• Inoue Noriko

  Graduate School Of Pharmaceutical Sciences The University Of Tokyo

• OHTA Kiminori

  Graduate School of Pharmaceutical Sciences, University of Tokyo

• KAWACHI Emiko

  Graduate School of Pharmaceutical Sciences, University of Tokyo

• Hashimoto Y

  Graduate School Of Pharmaceutical Sciences Kyushu University

• Fukasawa Hiroshi

  Graduate School Of Pharmaceutical Sciences The University Of Tokyo

• Hashimoto Yuichi

  Institute Of Molecular & Cellular Biosciences University Of Tokyo

• Kobayashi Hisayoshi

  Institute Of Molecular And Cellular Biosciences University Of Tokyo

• Ohya Kumiko

  Department Of Clinical Pharmacology And Toxicology Showa Pharmaceutical University

• Inoue Natsu

  Graduate School Of Pharmaceutical Sciences The University Of Tokyo

• Fukasawa H

  Graduate School Of Pharmaceutical Sciences The University Of Tokyo

• Kagechika H

  Tokyo Medical And Dental Univ. Tokyo Jpn

関連論文

• Coordination of Divalent Metal Cation to Amide Group to Form Adduct Ion in FAB Mass Spectrometry: Implication of Zn^ in Enzymatic Hydrolysis of Amide Bond
• Determination of Endogenous Levels of Retinoic Acid Isomers in Type II Diabetes Mellitus Patients. Possible Correlation with HbAlc Values(Analytical Biochemistry)
• Isolation and Structural Characterization of Siderophores, Madurastatins, Produced by a Pathogenic Actinomadura madurae
• Asterobactin, a New Siderophore Group Antibiotic from Nocardia asteoides
• Glycosylative Inactivation of Chalcomycin and Tylosin by a Clinically Isolated Nocardia asteroides Strain
• Structures of ADP-Ribosylated Rifampicin and Its Metabolite : Intermediates of Rifampicin-ribosylation by Mycobacterium smegmatis DSM43756
• ADVANCED COMPUTATIONAL DOCKING OF TWO TELEOCIDIN CONGENERS TO CYS2 DOMAIN OF PROTEIN KINASE Cδ
• Thermostability of Doubly Glycosylated Recombinant Lysozyme
• Expression and Characterization of Human Rheumatoid Factor Single-Chain FV
• Construction of the Single-Chain Fv from 196-14 Antibody toward Ovarian Cancer-Associated Antigen CA125
• Influence of Mutations of the N-Cap Residue, Gly4, on Stability and Structure of Hen Lysozyme
• Analysis of the Stabilization of Hen Lysozyme by Helix Macrodipole and Charged Side Chain Interaction
• Stabilization of Lysozyme by Introducing N-Glycosylation Signal Sequence
• A Mutation Study of Catalytic Residue Asp 52 in Hen Egg Lysozyme^1
• Correlation between the Differences in the Free Energy Change and conformational Energy in the Folded State of Hen Lysozymes with Gly-Pro and Pro-Gly Sequences Introduced to the Same Site
• Effect of Salt Concentration on the pK_a of Acidic Residues in Lysozyme
• 1P084 サリドマイド・アナログの抗インフルエンザウイルス活性(蛋白質-機能(反応機構,生物活性など),第48回日本生物物理学会年会)
• Docking Study of Bryostatins to Protein Kinase Cδ Cys2 Domain
• Pd2 SUPERPOSITION OF TELEOCIDINS AND PHORBOL ESTERS BY A NEW COMPUTATIONAL METHOD
• Structure Determination of Ribosylated Rifampicin and Its Derivative:New Inactivated Metabolites of Rifampicin by Mycobacterial Strains
• Isolation and Structures of an Antifungal Antibiotic, Fusarielin A, and Related Compounds Produced by a Fusarium sp.
• (Cis)-PREFERENCE OF N, N'-DIMETHYL-N, N'-DIPHENYLGUANIDINE AND THE GUANIDINIUM SALT. CONSTRUCTION OF WATER-SOLUBLE AROMATIC LAYERED STRUCTURE
• STERICAL PRORERTIES OF N, N'-DIMETHYLUREA MOIETY ENHANCE FORMATION OF TRIPLY HYDROGEN-BONDED COMPLEXES
• Enhancing Effect of Tumor Promoters, Phorbol Esters and Teleocidins on Nuclear Receptor-Mediated Transcription
• Identification of Protein Disulfide Isomerase as a Phorbol Ester-Binding Protein
• Dicarba-closo-dodecaboranes as a Pharmacophore. Novel Potent Retinoidal Agonists
• Dicarba-closo-dodecaboranes as a Pharmacophore. Retinoidal Antagonists and Potential Agonists
• Photoaffinity Labeling of Tumor Promoter-Binding Protein (CN-TPBP) and Preparation of Affinity Sorbent Gels
• Brasiliquinones A, B and C, New Benz[a]anthraquinone Antibiotics from Nocardia brasiliensis I. Producing Strain, Isolation and Biological Activities of the Antibiotics
• α-Glucosidase Inhibitors with a 4, 5, 6, 7-Tetrachlorophthalimide Skeleton Pendanted with a Cycloalkyl or Dicarba-closo-dodecaborane Group
• α-Glucosidase Inhibitors with a Phthalimide Skeleton : Stucture-Activity Relationship Study
• Modulators of Tumor Necrosis Factor α Production Bearing Dicarba-closo-dodecaborane as a Hydrophobic Pharmacophore
• Latent Enamine Functionality of 5-Methyl-2,3-dihydropyrazines
• Novel Retinoidal Tropolone Derivatives. Bioisosteric Relationship of Tropolone Ring with Benzoic Acid Moiety in Retinoid Structure
• Retinoidal Pyrimidinecarboxylic Acids. Unexpected Diaza-Substituent Effects in Retinobenzoic Acids
• Retinoid X Receptor-Antagonistic Diazepinylbenzoic Acids
• Thiazolidinediones with Thyroid Hormone Receptor Agonistic Activity
• NOVEL THIAZOLIDINEDIONE DERIVATIVES WITH RETINOID SYNERGISTIC ACTIVITY
• POTENT RETINOID SYNERGISTS WITH A DIPHENYLAMINE SKELETON
• Polyenylidine Thiazolidine Derivatives with Retinoidal Activities
• Photoaffinity Labeling of the Ligand-Interacting Helix of the Retinoic Acid Receptor Alpha
• Evaluation of Differentiation-Inducing Activity of Retinoids on Human Leukemia Cell Lines HL-60 and NB4
• NOVEL AROMATIC UREA DERIVATIVES WITH DNA-BINDING ABILITY
• DEIODOTRIFLUOROMETHYLATION OF ETHYL 3,3', 5-TRIIODOTHYROACETATE. DIVERGENT DERIVATIZATION BASED ON THE COMBINATORIAL CONCEPT
• New-Type Inducers of Differentiation of HL-60 Leukemia Cells Suppress c-myc Expression(Medeicinal Chemistry,Chemical)
• Antitumor Activity of Brasilicardin A, a Novel Terpenoid Antibiotic from Nocardia brasiliensis
• A New Antifungal Macrolide Component, Brasilinolide B, Produced by Nocardia brasiliensis
• Production of Erythromycin E by Pathogenic Nocardia brasiliensis
• Brasilicardin A, a New Terpenoid Antibiotic from Pathogenic Nocardia brasilienesis: Fermentation, Isolation, and Biological Activity
• Brasilicardin A ; a New Terpenoid Antibiotic Produced by Nocardia brasiliensis
• Brasilinolide A, a New Macrolide Antibiotic Produced by Nocardia brasiliensis: Producing Strain, Isolation and Biological Activity
• Different Rifampicin Inactivation Mechanisms in Nocardia and Related Taxa
• A Synthetic Retinoid Am80 (Tamibarotene) Rescues the Memory Deficit Caused by Scopolamine in a Passive Avoidance Paradigm(Communications to the Editor)
• Design and Synthesis of Phthalimide-Based Fluorescent Liver X Receptor Antagonists
• Structural Development of Benzhydrol-Type 1'-Acetoxychavicol Acetate (ACA) Analogs as Human Leukemia Cell-Growth Inhibitors Based on Quantitative Structure-Activity Relationship (QSAR) Analysis
• Structure-Based Design and Synthesis of Fluorescent PPARα/δ Co-agonist and Its Application as a Probe for Fluorescent Polarization Assay of PPARδ Ligands
• Fusarielin A as an Anti-angiogenic and Anti-proliferative Agent : Basic Biological Characterization
• Structural Development of Liver X Receptor (LXR) Antagonists Derived from Thalidomide-Related Glucosidase Inhibitors
• Development of Tubulin-Polymerization Inhibitors Based on the Thalidomide Skeleton
• Hydrolyzed Metabolites of Thalidomide : Synthesis and TNF-α Production-Inhibitory Activity
• Mono- and Dihydroxylated Metabolites of Thalidomide : Synthesis and TNF-α Production-Inhibitory Activity
• Effects of Immunomodulatory Derivatives of Thalidomide (IMiDs) and Their Analogs on Cell-Differentiation, Cyclooxygenase Activity and Angiogenesis
• Enhancement of All-trans Retinoic Acid-Induced HL-60 Cell Differentiation by Thalidomide and Its Metabolites(Communication to the Editor)
• N-Phenylphthalimide-Type Cyclooxygenase (COX) Inhibitors Derived from Thalidomide : Substituent Effects on Subtype Selectivity
• Thalidomide as a Nitric Oxide Synthase Inhibitor and Its Structural Development
• Conversion of Ca^ Salt of an Organic Compound to Its Li^+ Salt to Simplify the Fast Atom Bombardment Mass Spectrum
• Coordination of Sodium Cation to an Oxygen Function and Olefinic Double Bond to Form Molecular Adduct Ion in Fast Atom Bombardment Mass Spectrometry
• Separation of Phosphatidylinositol 4-Phosphate from a Mixture with Phosphatidylserine and Phosphatidylinositol by Sep-Pak C_ Cartridge
• Potent Homophthalimide-Type Inhibitors of B16F10/L5 Mouse Melanoma Cell Invasion
• Collisionally Activated Dissociation of 13-Membered Peptides, Ustiloxins, and Phomopsins
• Structural Identification of a Major Cytokinin in Coconut Milk as 14-O-{3-O-[β-D-Galactopyranosyl-(1→2)-α-D-galactopyranosyl-(1→3)-α-L-arabinofuranosyl]-4-O-(α-L-arabinofuranosyl)-β-D-galactopyranosyl}trans-zeatin Riboside
• Enhancement of Chemically-Induced HL-60 Cell Differentiation by 3,3′-Diindolylmethane Derivatives
• meso-DNAs with Homopurine Sequences : Analysis of Their Interaction with Natural DNAs
• Synthesis and Anti-tubulin Activity of Ustiloxin D Derivatives
• Isolation and Structure of an Antimitotic Cyclic Peptide, Ustiloxin F: Chemical Interrelation with a Homologous Peptide, Ustiloxin B
• Interaction of Arenastatin A with Porcine Brain Tubulin
• INDUCER-SPECIFIC REGULATORS OF TUMOR NECROSIS FACTOR ALPHA PRODUCTION
• AUGMENTATION BY PHTHALIMIDES OF PHORBOL ESTER-INDUCED EXPRESSION OF TUMOR NECROSIS FACTOR ALPHA MESSAGE
• Location of Two Photoaffinity-Labeled Sites on the Ligand-Binding Domain of Retinoic Acid Receptor α
• Phenylphthalimides with Tumor Necrosis Factor Alpha Production-Enhancing Activity
• Development of Novel Chiral Urea Catalysts for the Hetero-Michael Reaction
• Specific Nonpeptide Inhibitors of Puromycin-Sensitive Aminopeptidase with a 2,4(1H,3H)-Quinazolinedione Skeleton
• Cyclooxygenase Inhibitors Derived from Thalidomide
• Asymmetric Synthesis of a 3-Acyltetronic Acid Derivative, RK-682, and Formation of Its Calcium Salt during Silica Gel Column Chromatography
• Anti-Androgenic Activity of Substituted Azo- and Azoxy-Benzene Derivatives
• Antiangiogenic Activity of Tumor Necrosis Factor-α Production Regulators Derived from Thalidomide
• Tumor Necrosis Factor-Alpha Production Enhancing Activity of Substituted 3'-Methylthalidomide : Influence of Substituents at the Phthaloyl Moiety on the Activity and Stereoselectivity
• Modification by Heme Oxygenase Inhibitor, Tin Protoporphyrin, of Cellular Differentiation of Human Myeloid Leukemia K562 Cell Line
• Nucleophilic asymmetric epoxidation catalyzed by cyclic guanidines
• Structure-Activity Relationship of Bis-Galloyl Derivatives Related to (-)-Epigallocatechin Gallate
• Iron(III)Picolinate-Catalyzed Oxygenation of Cholesteryl Acetate with Hydrogen Peroxide or Peracetic Acid
• Identification of Binding Proteins of Fusarielin A as Actin and Tubulin
• Inhibition of Restriction Enzymes EcoRI, BamHI and HindIII by Phenethylphenylphthalimides Derived from Thalidomide
• Glycogen Phosphorylase a Inhibitors with a Phenethylphenylphthalimide Skeleton Derived from Thalidomide-Related α-Glucosidase Inhibitors and Liver X Receptor Antagonists
• Stereoselective Synthesis of Optically Active β-Lactams by the Reaction of Chiral Imines Derived from erythro-2-Amino-1,2-Diphenylethanol with Ester Enolates
• P-415 Target Protein Identification of Batzelladine A and D
• ILVIII-3 STRUCTURAL DEVELOPMENT STUDIES OF NUCLEAR RECEPTOR LIGANDS(Drug Discovery and Developments)
• Thymidine Phosphorylase Inhibitors with a Homophthalimide Skeleton
• Retinoic acids exert direct effects on T cells to suppress T_h1 development and enhance T_h2 development via retinoic acid receptors
• Organosilicon Compounds as Adult T-Cell Leukemia Cell Proliferation Inhibitors

もっと見る 閉じる

スポンサーリンク