4-羟基-5-甲基-7-硝基-2,3-二氢-1H-茚 | 575504-26-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 茚满类
• 中文名称: 4-羟基-5-甲基-7-硝基-2,3-二氢-1H-茚
• 英文名称: 5-methyl-7-nitroindan-4-ol
• 英文别名: 5-Methyl-7-nitro-2,3-dihydro-1H-inden-4-ol
• CAS: 575504-26-6
• 化学式: C₁₀H₁₁NO₃
• 分子量: 193.202
• InChiKey: BJMAIIRQVRRZMF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  14
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  66
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-羟基-5-甲基-7-硝基-2,3-二氢-1H-茚 在 吡啶 、 三氟甲磺酸酐 、 palladium 10% on activated carbon 、 氢气 、 铜 、 三乙胺 作用下， 以 二氯甲烷 、 乙酸乙酯 为溶剂， 反应 138.0h， 生成 ethyl N-[7-(4-methoxy-3-phenylacetylphenoxy)-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
• 作为产物：
  描述：

  5-甲基-2,3-二氢-1H-茚-4-醇 在 硝酸 、 溶剂黄146 作用下， 以 水 为溶剂， 以19%的产率得到4-羟基-5-甲基-7-硝基-2,3-二氢-1H-茚
  参考文献：
  名称：

  发现用于治疗血脂异常的新型茚满衍生物作为肝脏选择性甲状腺激素受体β（TRβ）激动剂

  摘要：

  在动物模型中，特异靶向TRβ的拟胸腺激素可降低血浆胆固醇水平，并通过促进胆固醇逆向转运来避免动脉粥样硬化。我们基于eprotirome（3）的结构和分子模型设计了具有高受体（TRβ）和器官（肝）选择性的新型甲状腺素组学。我们发现，茚满衍生物是有效的双选择甲状腺素药物，有望避免某些组织的甲状腺功能减退以及心脏毒性。KTA-439（29），具有代表性的二氢化茚衍生物，表现出相同的高人类TRβ选择性在结合测定如3和更高的肝选择性比3在胆固醇喂养的大鼠模型。

  DOI：

  10.1016/j.bmc.2012.03.056

文献信息

• Novel Compounds
  申请人：Chhipa Laxmikant

  公开号：US20100168110A1

  公开（公告）日：2010-07-01

  The present invention discloses a novel thyroid like compounds of formula (I), wherein R 1 R 2 , R 3 , R 4 and Z are as defined in the specification, method for its preparation, composition containing such compounds and use of such compounds and composition as medicament. Further, compounds of formula (I) has significantly low binding affinity to thyroid receptors and thus considerably devoid of thyrotoxic effects. The invention also relates to the use of the compound of formula (I) for the preparation of a medicament for treating various disease conditions such as obesity, dyslipidemia, metabolic syndrome and co-morbidities associated with metabolic syndrome.

  本发明公开了一种新型的甲状腺类似化合物，其化学式为（I），其中R1、R2、R3、R4和Z如规范中所定义，以及其制备方法、含有这种化合物的组合物和这种化合物及组合物作为药物的用途。此外，化合物的化学式（I）具有与甲状腺受体显著低的结合亲和力，因此在很大程度上缺乏甲状腺毒性作用。该发明还涉及将化学式（I）的化合物用于制备用于治疗肥胖、血脂异常、代谢综合征以及与代谢综合征相关的合并症等各种疾病状况的药物。
• 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。
• Thyroid hormone receptor ligand, medicinal compositions containing the same and use thereof
  申请人：Kissei Pharmaceutical Co., Ltd.

  公开号：US07230031B2

  公开（公告）日：2007-06-12

  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，低烷基，卤代低烷基，CN等；R3为氢等；R4为氢，卤素，烷基，卤代低烷基，取代烷基，芳香基，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；含有它们的制药组合物及其用途，其具有与人类甲状腺激素受体，特别是人类甲状腺激素受体β高亲和力的特点。
• NOVEL COMPOUNDS
  申请人：Chhipa Laxmikant

  公开号：US20120202816A1

  公开（公告）日：2012-08-09

  The present invention discloses a novel thyroid like compounds of formula (I), wherein R 1 R 2 , R 3 , R 4 and Z are as defined in the specification, method for its preparation, composition containing such compounds and use of such compounds and composition as medicament. Further, compounds of formula (I) has significantly low binding affinity to thyroid receptors and thus considerably devoid of thyrotoxic effects. The invention also relates to the use of the compound of formula (I) for the preparation of a medicament for treating various disease conditions such as obesity, dyslipidemia, metabolic syndrome and co-morbidities associated with metabolic syndrome.

  本发明揭示了一种新型的类甲状腺化合物，其化学式为（I），其中R1R2、R3、R4和Z的定义如规范中所述，以及其制备方法、含有该类化合物的组合物以及该类化合物和组合物作为药物的用途。此外，化合物（I）具有显著低的甲状腺受体结合亲和力，因此明显缺乏甲状腺毒性作用。本发明还涉及将化合物（I）用于制备治疗肥胖、血脂异常、代谢综合征和与代谢综合征相关的共病症的药物的用途。
• 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。