Studies on Aromatase Inhibitors. I. Synthesis and Biological Evaluation of 4-Amino-4H-1,2,4-triazole Derivatives

スポンサーリンク

概要

• 論文の詳細を見る

• Various 4-N-substituted amino-4H-1,2,4-triazole derivatives were synthesized and evaluated for aromatase-inhibitory activity (in vitro) and for pregnant mare serum gonadotropin (PMSG)-induced estrogen synthesis-inhibitory activity (in vivo). The 4-(4-cyanophenyl) amino derivative and 4-(4-nitrophenyl)amino derivative, each possessing a strong electron-withdrawing group on the phenyl moiety, showed potent aromatase-inhibitory activity. Structure-activity relationship studies indicated that 4-[(4-bromobenzyl)(4-cyanophenyl)amino]-4H-1,2,4-triazole (5k, YM511) is a highly potent aromatase inhibitor with IC_<50> values of 0.4 and 0.12 nM in in vitro experiments using rat ovary and human placenta, respectively, and an in vivo ED_<50>of 0.002 mg/kg in rats on oral administration.YM511 was also a weak inhibitor of other steroid hormone synthesis enzymes. These data suggest that YM511 is a highly selective aromatase inhibitor and may be a useful agent for the treatment of estrogen-dependent diseases such as breast cancer.

• 公益社団法人日本薬学会の論文
• 1996-10-15

著者

• Okada M

  Institute For Drug Discovery Research Yamanouchi Pharmaceutical Co. Ltd.

• Isomura Y

  Yamanouchi Pharmaceutical Co. Ltd. Ibaraki Jpn

• OKADA Minoru

  Endocrinology

• YODEN Toru

  Metabolic Disease Laboratories Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co.,

• KAWAMINAMI Eiji

  Endocrinology

• SHIMADA Yoshiaki

  Metabolic Disease Laboratories Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co.,

• KUDOH Masafumi

  Endocrinology

• ISOMURA Yasuo

  Metabolic Disease Laboratories Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co.,

• SHIKAMA Hisataka

  Endocrinology

• FUJIKURA Takashi

  Metabolic Disease Laboratories Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co.,

• SHIMADA Yasuo

  Mitsuboshi Pharmacutical Co.

• Yoden T

  Institute For Technology Development Yamanouchi Pharmaceutical Co. Ltd.

• Shimada Y

  Mitsuboshi Pharmaceutical Co

• Kudoh Masafumi

  Drug Discovery Research Astellas Pharma Inc.

• Kawaminami Eiji

  Medicinal Chemistry Research Ii Institute For Drug Discovery Research Yamanouchi Pharmaceutical Co.

• FURUTANI Takashi

  Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co., Ltd.

• Furutani Takashi

  Drug Discovery Research Astellas Pharma Inc.

• Shikama H

  Yamanouchi Pharmaceutical Co. Ltd. Ibaraki Jpn

関連論文

• Peptide Based Interleukin-1β Converting Enzyme (ICE) Inhibitors : Synthesis, Structure Activity Relationships and Crystallographic Study of the ICE-inhibitor Complex
• YM116, 2-(lH-Imidazol-4-ylmethyl)-9H-carbazole, Decreases Adrenal Androgen Synthesis by Inhibiting C17-20 Lyase Activity in NCI-H295 Human Adrenocortical Carcinoma Cells
• Studies on Aromatase Inhibitors IV. Synthesis and Biological Evaluation of N, N-Disubstituted-5-aminopyrimidine Derivatives
• Studies on Aromatase Inhibitors. III. Synthesis and Biological Evaluation of [(4-Bromobenzyl)(4-cyanophenyl)amino]azoles and Their Azine Analogs
• Studies on Aromatase Inhibitors. II. Synthesis and Biological Evaluation of 1-Amino-1H-1,2,4-triazole Derivatives
• Studies on Aromatase Inhibitors. I. Synthesis and Biological Evaluation of 4-Amino-4H-1,2,4-triazole Derivatives
• Field Survey of Cinnamon in Viet Nam
• Four New 2-(2-Phenylethyl)chromone Derivatives from Withered Wood of Aquilaria sinensis
• Antiproliferative Sesquiterpene Lactones from the Roots of Inula helenium(Pharmacognosy)
• Spiro-Substituted Piperidines as Neurokinin Receptor Antagonists. III. Synthesis of (±)-N-[2-(3,4-Dichlorophenyl)-4-(spiro-substituted piperidin-1'-yl)butyl]-N-methylbenzamides and Evaluation of NK_1-NK_2 Dual Antagonistic Activities
• Spiro-Substituted Piperidines as Neurokinin Receptor Antagonists. I. Design and Synthesis of (±)-N-[2-(3,4-Dichlorophenyl)-4-(spiro[isobenzofuran-1(3H), 4'-piperidin]-1'-yl)butyl]-N-methylbenzamide, YM-35375,as a New Lead Compound for Novel Neurokinin Rec
• Six New 2-(2-Phenylethyl)chromones from Agarwood
• Three New Labdane-Type Diterpenes from Wood, Excoecaria agallocha
• Studies on Novel Bone Resorption Inhibitors. II. Synthesis and Pharmacological Activities of Fused Aza-heteroarylbisphosphonate Derivatives
• Telomerase Is Upregulated in Irreversible Preneoplastic Lesions during Bladder Carcinogenesis in Rats
• Selective Muscarinic Antagonists. II. Synthesis and Antimuscarinic Properties of Biphenylylcarbamate Derivatives
• Selective Muscarinic Antagonists. I. Synthesis and Antimuscarinic Properties of 4-Piperidyl Benzhydrylcarbamate Derivatives
• Spiro-Substituted Piperidines as Neurokinin Receptor Antagonists. II. Syntheses and NK_2 Receptor-Antagonistic Activities of N-[2-Aryl-4-(spiro-substituted piperidin-1'-yl)butyl]carboxamides
• N-Arylpiperazine-1-carboxamide Derivatives : a Novel Series of Orally Active Nonsteroidal Androgen Receptor Antagonists
• Synthesis and Pharmacological Evaluation of Novel Arylpiperazine Derivatives as Nonsteroidal Androgen Receptor Antagonists
• A Role of Androgen Receptor Protein in Cell Growth of an Androgen-Independent Prostate Cancer Cell Line
• RNA-Binding Protein Hoip Accelerates PolyQ-Induced Neurodegeneration in Drosophila
• Prevention of Bone Loss by Bisphosphonate YM175 in Ovariectomized Dogs with Dietary Calcium Restriction
• Field Survey of Cinnamon in Viet Nam
• Non-invasive and Time-Resolved Observation of Tumors Implanted in Living Mice by Using Phase-Contrast X-ray Computed Tomography

もっと見る 閉じる

スポンサーリンク