ethyl N-(7-{3-[2-(4-fluorophenyl)ethyl]-4-hydroxyphenoxy}-6-methylindan-4-yl)malonamate | 575503-56-9

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 二苯乙烯类
• 英文名称: ethyl N-(7-{3-[2-(4-fluorophenyl)ethyl]-4-hydroxyphenoxy}-6-methylindan-4-yl)malonamate
• 英文别名: ethyl 3-[[7-[3-[2-(4-fluorophenyl)ethyl]-4-hydroxyphenoxy]-6-methyl-2,3-dihydro-1H-inden-4-yl]amino]-3-oxopropanoate
• CAS: 575503-56-9
• 化学式: C₂₉H₃₀FNO₅
• 分子量: 491.559
• InChiKey: TXDVGRASOATLIK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.7
• 重原子数：
  36
• 可旋转键数：
  10
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  84.9
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  ethyl N-(7-{3-[2-(4-fluorophenyl)ethyl]-4-hydroxyphenoxy}-6-methylindan-4-yl)malonamate 在 水 、 sodium hydroxide 作用下， 以 甲醇 为溶剂， 反应 0.5h， 生成 N-(7-{3-[2-(4-fluorophenyl)ethyl]-4-hydroxyphenoxy}-6-methylindan-4-yl)malonamic acid
  参考文献：
  名称：

  Design, synthesis, and structure–activity relationship (SAR) of N-[7-(4-hydroxyphenoxy)-6-methylindan-4-yl]malonamic acids as thyroid hormone receptor β (TRβ) selective agonists

  摘要：

  Highly TR beta selective thyromimetics have several potential therapeutic applications. Based on the novel indane derivative KTA-439 with high receptor (TR beta) and organ (liver) selectivity, a series of thyroid hormone analogues were prepared, in which the isopropyl at the 3'-position was replaced with alkyl and aralkyl moieties of variable lengths and branches. Binding assays for these human TRs and reporter cell assays showed that 2-arylethyl derivatives had higher TR beta selectivity than KTA-439. KTA-574, a representative 2-arylethyl derivative, had TR beta specificity in a binding assay and exhibited full agonism in a reporter cell assay. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2012.12.002
• 作为产物：
  描述：

  ethyl N-[7-(4-methoxyphenoxy)-6-methylindan-4-yl]malonamate 在 三乙基硅烷 、 三氟甲磺酸酐 、 三氯化硼 、 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 87.0h， 生成 ethyl N-(7-{3-[2-(4-fluorophenyl)ethyl]-4-hydroxyphenoxy}-6-methylindan-4-yl)malonamate
  参考文献：
  名称：

  Design, synthesis, and structure–activity relationship (SAR) of N-[7-(4-hydroxyphenoxy)-6-methylindan-4-yl]malonamic acids as thyroid hormone receptor β (TRβ) selective agonists

  摘要：

  Highly TR beta selective thyromimetics have several potential therapeutic applications. Based on the novel indane derivative KTA-439 with high receptor (TR beta) and organ (liver) selectivity, a series of thyroid hormone analogues were prepared, in which the isopropyl at the 3'-position was replaced with alkyl and aralkyl moieties of variable lengths and branches. Binding assays for these human TRs and reporter cell assays showed that 2-arylethyl derivatives had higher TR beta selectivity than KTA-439. KTA-574, a representative 2-arylethyl derivative, had TR beta specificity in a binding assay and exhibited full agonism in a reporter cell assay. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2012.12.002

文献信息

• Novel thyroid hormone receptor ligand, medicinal compositions containing the same and use thereof
  申请人：Shiohara Hiroaki

  公开号：US20050085541A1

  公开（公告）日：2005-04-21

  The present invention provides a compound represented by general formula (I): or pharmaceutically acceptable salts thereof, wherein W is O, S(O) m , CH 2 and the like; R 1 is halogen, lower alkyl, halo-lower alkyl, CN and the like; R 3 is hydrogen and the like; R 4 is hydrogen, halogen, alkyl, halo-lower alkyl, substituted alkyl, aryl, aralkyl, alkoxy, substituted alkoxy, alkanoyl, aroyl, —CONR 7 (R 8 ), —S(O) m R 9 , —SO 2 NR 7 (R 8 ) and the like; R 5 is hydrogen, halogen, alkyl, substituted alkyl and the like; A is —N(R 6 )CO-A 1 -COR 10 and the like; pharmaceutical compositions containing them and their uses, which have a high affinity to human thyroid hormone receptors, in particular human thyroid hormone receptor β.

  本发明提供了一种由通式（I）表示的化合物，或其药学上可接受的盐，其中W为O，S（O）m，CH2等；R1为卤素，低碳基，卤代低碳基，CN等；R3为氢等；R4为氢，卤素，烷基，卤代低碳基，取代烷基，芳基，芳基烷基，烷氧基，取代烷氧基，烷酰基，芳酰基，-CONR7（R8），-S（O）mR9，-SO2NR7（R8）等；R5为氢，卤素，烷基，取代烷基等；A为-N（R6）CO-A1-COR10等；含有它们的药物组合物及其用途，具有高亲和力与人类甲状腺激素受体，特别是人类甲状腺激素受体β。
• NOVEL THYROID HORMONE RECEPTOR LIGAND, MEDICINAL COMPOSITIONS CONTAINING THE SAME AND USE THEREOF
  申请人：Kissei Pharmaceutical Co., Ltd.

  公开号：EP1471049A1

  公开（公告）日：2004-10-27

  The present invention provides a compound represented by general formula (I): . or pharmaceutically acceptable salts thereof, wherein W is O, S(O)m, CH2 and the like: R1 is halogen, lower alkyl, halo-lower alkyl, CN and the like; R3 is hydrogen and the like; R4 is hydrogen, halogen, alkyl, halo-lower alkyl, substituted alkyl, aryl, aralkyl, alkoxy, substituted alkoxy, alkanoyl, aroyl, -CONR7(R8), - S(O)mR9, -SO2NR7(R8) and the like; R5 is hydrogen, halogen, alkyl, substituted alkyl and the like; A is -N(R6)CO-A1-COR10 and the like; pharmaceutical compositions containing them and their uses, which have a high affinity to human thyroid hormone receptors, in particular human thyroid hormone receptor β.

  本发明提供了通式（I）代表的化合物：. 或其药学上可接受的盐，其中 W 是 O、S(O)m、CH2 等：R1 是卤素、低级烷基、卤代低级烷基、CN 和类似物；R3 是氢和类似物；R4 是氢、卤素、烷基、卤代低级烷基、取代烷基、芳基、芳烷基、烷氧基、取代烷氧基、烷酰基、芳基、-CONR7(R8)、-S(O)mR9、-SO2NR7(R8)和类似物；R5 是氢、卤素、烷基、取代烷基及类似物；A 是-N(R6)CO-A1-COR10 及类似物；含有它们的药物组合物及其用途，对人类甲状腺激素受体，特别是人类甲状腺激素受体 β 具有高亲和力。
• US7230031B2
  申请人：——

  公开号：US7230031B2

  公开（公告）日：2007-06-12
• Design, synthesis, and structure–activity relationship (SAR) of N-[7-(4-hydroxyphenoxy)-6-methylindan-4-yl]malonamic acids as thyroid hormone receptor β (TRβ) selective agonists
  作者：Hiroaki Shiohara、Tetsuya Nakamura、Norihiko Kikuchi、Tomonaga Ozawa、Akane Matsuzawa、Ryuichi Nagano、Hideki Ohnota、Takahide Miyamoto、Kazuo Ichikawa、Kiyoshi Hashizume

  DOI：10.1016/j.bmc.2012.12.002

  日期：2013.2

  Highly TR beta selective thyromimetics have several potential therapeutic applications. Based on the novel indane derivative KTA-439 with high receptor (TR beta) and organ (liver) selectivity, a series of thyroid hormone analogues were prepared, in which the isopropyl at the 3'-position was replaced with alkyl and aralkyl moieties of variable lengths and branches. Binding assays for these human TRs and reporter cell assays showed that 2-arylethyl derivatives had higher TR beta selectivity than KTA-439. KTA-574, a representative 2-arylethyl derivative, had TR beta specificity in a binding assay and exhibited full agonism in a reporter cell assay. (C) 2012 Elsevier Ltd. All rights reserved.