CCR5 Antagonists as Anti-HIV-1 Agents.1. Synthesis and Biological Evaluation of 5-Oxopyrrolidine-3-carboxamide Derivatives
スポンサーリンク
概要
- 論文の詳細を見る
A novel lead compound, Ar-{3-[4-(4-fluorobenzoyl)piperidin-1-yl]propyl}-1-methyl-5-oxo-N-phenylpyrrolidine-3-carboxamide (1), was identified as a CCR5 antagonist by high-throughput screening using [^<125>I]RANTES and CCRS-expressing CHO cells. The IC_<50> value of 1 was 1.9 μM. In an effort to improve the binding affinity of 1, a series of 5-oxopyrrolidine-3-carboxamides was synthesized. Introduction of 3,4-dichloro substituents to the central phenyl ring (10i, IC_<50>=0.057 μM; lib, IC_<50>=0.050 μM) or replacing the 1-methyl group of the 5-oxopyrrolidine moiety with a 1-benzyl group (12e, IC_<50>=0.038 μM) was found to be effective for improving CCR5 affinity. Compound 10i, 11b, and 12e also inhibited CCR5-using HIV-1 envelope-mediated membrane fusion with IC_<50> values of 0.44, 0.19, and 0.49 μM, respectively.
- 公益社団法人日本薬学会の論文
- 2004-01-01
著者
-
KANZAKI Naoyuki
Takeda Chemical Industries, Ltd., Pharmaceutical Research Division
-
Iizawa Y
武田薬品工業
-
Iizawa Yuji
Pharmacology Research Laboratories I Pharmaceutical Research Division Takeda Chemical Industries Ltd
-
Kanzaki Naoyuki
Pharmaceutical Research Division Takeda Chemical Industries Ltd.
-
Kanzaki Naoyuki
Takeda Chemical Industries Ltd. Pharmaceutical Research Division
-
MATSUSHITA Yoshihiro
Pharmaceutical Research Laboratories III, Pharmaceutical Research Division, Takeda Chemical Industri
-
BABA Masanori
Division of Antiviral Chemotherapy, Center for Chronic Viral Diseases, Faculty of Medicine, Kagoshim
-
IMAMURA Shinichi
Pharmaceutical Research Division, Takeda Chemical Industries, Ltd.
-
ISHIHARA Yuji
Pharmaceutical Research Division, Takeda Chemical Industries, Ltd.
-
HATTORI Taeko
Pharmaceutical Research Division, Takeda Chemical Industries, Ltd.
-
KURASAWA Osamu
Pharmaceutical Research Division, Takeda Chemical Industries, Ltd.
-
SUGIHARA Yoshihiro
Pharmaceutical Research Division, Takeda Chemical Industries, Ltd.
-
HASHIGUCHI Shohei
Division of Antiviral Chemotherapy, Center for Chronic Viral Diseases, Faculty of Medicine, Kagoshim
-
Baba M
Department Of Natural Medicine And Phytochemistry Meiji Pharmaceutical University
-
Hattori Taeko
Pharmaceutical Research Division Takeda Chemical Industries Ltd.
-
Hashiguchi Shohei
Division Of Antiviral Chemotherapy Center For Chronic Viral Diseases Faculty Of Medicine Kagoshima U
-
Ishihara Yuji
Pharmaceutical Research Division Takeda Chemical Industries Ltd.
-
Kurasawa Osamu
Pharmaceutical Research Division Takeda Chemical Industries Ltd.
-
Matsushita Y
Pharmaceutical Research Division Takeda Chemical Industries Ltd.
-
Sugihara Yoshihiro
Pharmaceutical Research Division Takeda Chemical Industries Ltd.
-
Imamura S
Pharmaceutical Research Division Takeda Chemical Industries Ltd.
関連論文
- The Chemokine Receptor CXCR4 as a Therapeutic Target for Several Diseases Including AIDS, Cancer and Rheumatoid Arthritis
- CXCR4 Antagonists Identified as Anti-Cancer-Metastatic Agents
- 抗エイズウイルス活性を有する親水性フルオロシランカップリングオリゴマ-の合成
- Optically Active Antifungal Azoles. III. Synthesis and Antifungal Activity of Sulfide and Sulfonamide Derivatives of (2R, 3R)-2-(2,4-Difluorophenyl)-3-mercapto-1-(1H, 1,2,4-triazol-1-yl)-2-butanol
- Optically Active Antifungal Azoles. I. Synthesis and Antifungal Activity of (2R, 3R)-2-(2,4-Difluorophenyl)-3-mercapto-1-(1H-1,2,4-triazol-1-yl)-2-butanol and Its Stereoisomers
- Synthesis and Biological Activities of 4-Phenyl-5-pyridyl-1,3-thiazole Derivatives as Selective Adenosine A_3 Antagonists
- Synthesis and Biological Activity of (S)-2-Amino-3-(2,5-dihydro-5-oxo-4-isoxazolyl)propanoic Acid (TAN-950 A) Derivatives
- Orally Active CCR5 Antagonists as Anti-HIV-1 Agents : Synthesis and Biological Activity of 1-Benzothiepine 1, 1-Dioxide and 1-Benzazepine Derivatives Containing a Tertiary Amine Moiety
- Optically Active Antifungal Azoles. VII. Synthesis and Antifungal Activity of Stereoisomers of 2-[(1R, 2R)-2-(2,4-Difluorophenyl)-2-hydroxy-1-methyl-3-(1H-1,2,4-triazol-1-yl)propyl]-4-[4-(2,2,3,3-tetrafluoropropoxy)phenyl]-3(2H, 4H)-1,2,4-triazolone (TAK-
- Optically Active Antifungal Azoles. VI. Synthesis and Antifungal Activity of N-[(1R, 2R)-2-(2,4-Difluorophenyl)-2-hydroxy-1-methyl-3-(1H-1,2,4-triazol-1-yl)propyl]-N'-(4-substituted phenyl)-3(2H, 4H)-1,2,4-triazolones and 5(1H, 4H)-tetrazolones
- Orally Active CCR5 Antagonists as Anti-HIV-1 Agents 2 : Synthesis and Biological Activities of Anilide Derivatives Containing a Pyridine N-Oxide Moiety
- Synthesis of 1-Benzothiepine and 1-Benzazepine Derivatives as Orally Active CCR5 Antagonists
- CCR5 Antagonists as Anti-HIV-1 Agents.1. Synthesis and Biological Evaluation of 5-Oxopyrrolidine-3-carboxamide Derivatives
- In vitro antimicrobial activity of T-91825, a novel anti-MRSA cephalosporin, and in vivo anti-MRSA activity of its prodrug, TAK-599
- Studies on Anti-MRSA Parenteral Cephalosporins : IV. A Novel Water-soluble N-Phosphono Type Prodrug for Parenteral Administration
- Studies on Anti-MRSA Parenteral Cephalosporins : III. Synthesis and Antibacterial Activity of 7β-[2-(5-Amino-1,2,4-thiadiazol-3-yl)-2(Z)-alkoxyiminoacetamido]-3-[(E)-2-(1-alkylimidazo[1,2-b]pyridazinium-6-yl)thiovinyl]-3-cephem-4-carboxylates and Related
- Studies on Anti-MRSA Parenteral Cephalosporins : II. Synthesis and Antibacterial Activity of 7β-[2-(5-Amino-1,2,4-thiadiazol-3-yl)-2(Z)-alkoxyiminoacetamido]-3-(substituted imidazo[1,2-b]pyridazinium-1-yI)methyl-3-cephem-4-carboxylates and Related Compoun
- Studies on Anti-MRSA Parenteral Cephalosporins : I. Synthesis and Antibacterial Activity of 7β-[2-(5-Amino-1,2,4-thiadiazol-3-yl)-2(Z)-hydroxyiminoacetamido]-3-(substituted imidazo[1,2-b]-pyridazinium-1-yl)methyl-3-cephem-4-carboxylates and Related Compou
- Optically Active Antifungal Azoles. II. Synthesis and Antifungal Activity of Polysulfide Derivatives of (2R, 3R)-2-(2,4-Difluorophenyl)-3-mercapto-1-(1H-1,2,4-triazol-1-yl)-2-butanol
- EM2487, a Novel Anti - HIV - 1 Antibiotic, Produced by Streptomyces sp. Mer - 2487: Taxonomy, Fermentation, Biological Properties, Isolation and Structure Elucidation
- Synthesis and Anti-HIV-1 Activity of Novel 10-Thiaisoalloxazines, a Structural Analog of C-5 and/or C-6 Substituted Pyrimidine Acyclonucleoside
- Different Properties of Wild Type and Drug-Resistant Mutants of Human Immunodeficiency Virus Type 1 Reverse Transcriptase In Vitro
- Anti-rheumatic compound aurothioglucose inhibits tumor necrosis factor-α-induced HIV-1 replication in latently infected OM10.1 and Ach2 cells
- Synthesis and Properties of Gelling Fluoroalkylated End-Capped Oligomers Containing Hydroxy Segments
- Syntheses and Properties of Fluoroalkylated Oligomers Containing Oligo(oxyethylene) Units
- Sho-Saiko-To, a Traditional Kampo Medicine, Enhances the Anti-HIV-1 Activity of Lamivudine(3TC)In Vitro
- Thermophoresis of a Circular Cylinder in a Rarefied Gas
- Stereoselective Synthesis of 4'-α-Alkylcarbovir Derivatives Based on an Asymmetric Synthesis or Chemoenzymatic Procedure
- Synthesis and Anti-human Immunodeficiency Virus Activity of the Skeleton Isomers of 3′,4′-Di-(O)-(−)-camphanoyl-(+)-khellactone
- Organosilicon Compounds as Adult T-Cell Leukemia Cell Proliferation Inhibitors