4-bromo-2-isopropyl-1-triisopropylsilanyloxybenzene | 253329-09-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 4-bromo-2-isopropyl-1-triisopropylsilanyloxybenzene
• 英文别名: (4-bromo-2-isopropyl-phenoxy)-tri-isopropylsilane；(4-bromo-2-isopropylphenoxy)triisopropylsilane；3-isopropyl-4-triisopropylsilylbromobenzene；3-isopropyl-4-triisopropylsilyloxy-bromobenzene；(4-bromo-2-propan-2-ylphenoxy)-tri(propan-2-yl)silane
• CAS: 253329-09-8
• 化学式: C₁₈H₃₁BrOSi
• 分子量: 371.433
• InChiKey: QBRRLXLEIKYIKV-UHFFFAOYSA-N

物化性质

• 沸点：
  358.9±35.0 °C(Predicted)
• 密度：
  1.065±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  7.13
• 重原子数：
  21
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  9.2
• 氢给体数：
  0
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  4-bromo-2-isopropyl-1-triisopropylsilanyloxybenzene 在 palladium on activated charcoal 吡啶 、 bis-triphenylphosphine-palladium(II) chloride 、 正丁基锂 、 氢气 、 臭氧 、 lithium chloride 作用下， 以 四氢呋喃 、 乙醇 、 正己烷 、 二氯甲烷 、 乙酸乙酯 、 N,N-二甲基甲酰胺 为溶剂， -78.0~60.0 ℃ 、241.32 kPa 条件下， 反应 31.5h， 生成 4-[3-isopropyl-4-(triisopropylsilyloxy)benzyl]-3,5-dimethylbenzaldehyde
  参考文献：
  名称：

  Structural Determinants of Selective Thyromimetics

  摘要：

  The thyromimetic GC-1 shows a preference for binding the P form of the thyroid hormone receptor (TR). GC-1 was designed as an analogue of the thyromimetic DIMIT, which has alower affinity for TR and is not selective. GC-1 has a methylene group linking its two aromatic rings and an oxyacetic acid polar side chain, while DIMIT has an ether oxygen linking its aromatic rings and an L-alanine polar side chain. The structural features of GC-1 that confer its greater affinity and selectivity compared to DIMIT were analyzed with the preparation of analogues that bear only one of their two different structural features. The analogue of GC-1 with a biaryl ether has selectivity comparable to that of GC-1, while the analogue of DIMIT with a methylene group linking its aromatic rings is only slightly selective. These results demonstrate that the oxyacetic acid side chain of GC-1 is critical in conferring TR-beta selectivity.

  DOI：

  10.1021/jm0301181
• 作为产物：
  描述：

  异丙苯酚 在 咪唑 、 氢溴酸 、 溶剂黄146 作用下， 以 二甲基亚砜 为溶剂， 生成 4-bromo-2-isopropyl-1-triisopropylsilanyloxybenzene
  参考文献：
  名称：

  设计和合成新型的[1-（4-羟基-苄基）-1 H-吲哚-5-基氧基]-乙酸化合物，作为有效的，选择性的甲状腺激素受体β激动剂

  摘要：

  描述了一系列新颖的吲哚作为有效的，选择性的甲状腺激素受体β（TRβ）激动剂的设计，合成和结构活性关系。产生了对TRβ的相对于TRα具有> 50x结合选择性的化合物，并且在血脂异常模型中对该系列化合物1c的评估显示了对体内血浆脂质终点的积极作用。

  DOI：

  10.1016/j.bmcl.2015.02.062

文献信息

• NOVEL 6-5 BICYCIC HETEROCYCLIC DERIVATIVE AND MEDICAL USE THEREOF
  申请人：Sanwa Kagaku Kenkyusho Co., Ltd

  公开号：EP2036887A1

  公开（公告）日：2009-03-18

  An object of the present invention is to provide a medicament as a thyroid hormone receptor ligand which is sufficient in drug efficacy and safety, and has the excellent action as a drug. The present invention provides a compound represented by the following general formula (I) or a pharmaceutically acceptable salt thereof: [wherein [Chemical Formula 2] is a single bond or a double bond; A is -CH2- or -CO-; X, Y, and Z are each independently a nitrogen atom or a carbon atom; R1 is a hydrogen atom or an aralkyl group; R2 is an alkyl group or an aralkyl group, etc.; R3 is a hydrogen atom or an alkyl group, etc.; R4 is a hydrogen atom or an alkyl group; R5 is a hydrogen atom, an alkyl group or a halo lower alkyl group, etc.; R6 is a hydrogen atom or an alkyl group; R7 is a hydrogen atom, etc.; R8 is a hydrogen atom, or an alkyl group, etc.; and E is -NHCO-G-COR12, etc. (wherein G is a single bond or an alkylene group, and R12 is a hydroxy group or an alkoxy group)].

  本发明的目的是提供一种药物，作为甲状腺激素受体配体，其在药物疗效和安全性上足够，并且具有作为药物的优秀作用。本发明提供了一种由以下通式（I）表示的化合物或其药用可接受的盐：[其中[化学公式2]是单键或双键；A是-CH2-或-CO-；X、Y和Z各自独立为氮原子或碳原子；R1是氢原子或芳烷基团；R2是烷基团或芳烷基团等；R3是氢原子或烷基团等；R4是氢原子或烷基团；R5是氢原子、烷基团或卤素低烷基团等；R6是氢原子或烷基团；R7是氢原子等；R8是氢原子或烷基团等；E是-NHCO-G-COR12等（其中G是单键或亚烷基团，R12是羟基或烷氧基）]。
• Systemic optimization and structural evaluation of quinoline derivatives as transthyretin amyloidogenesis inhibitors
  作者：Boyoung Kim、Hwanggue Park、Seul Ki Lee、Sung Jean Park、Tae-Sung Koo、Nam Sook Kang、Ki Bum Hong、Sungwook Choi

  DOI：10.1016/j.ejmech.2016.08.003

  日期：2016.11

  Wild type transthyretin (TTR) and mutant TTR misfold and misassemble into a variety of extracellular insoluble amyloid fibril and/or amorphous aggregate, which are associated with a variety of human amyloid diseases. To develop potent TTR amyloidogenesis inhibitors, we have designed and synthesized a focused library of quinoline derivatives by Pd-catalyzed coupling reaction and by the Horner–Wadsworth–Emmons

  野生型运甲状腺素蛋白（TTR）和突变体TTR错折叠和错配成各种细胞外不溶性淀粉样原纤维和/或无定形聚集体，它们与多种人类淀粉样蛋白疾病有关。为了开发有效的TTR淀粉样生成抑制剂，我们设计并合成了Pd催化的偶联反应和Horner-Wadsworth-Emmons反应的喹啉衍生物库。通过利用酸介导的TTR原纤维形成，评价了所得的2-炔基喹啉衍生物，（E）-2-烯基喹啉衍生物和（E）-3-烯基喹啉衍生物抑制TTR淀粉样蛋白生成。在这些喹啉衍生物中，化合物14c显示出最有效的抗-TTR原纤维形成活性在筛选研究中，针对WT-TTR的IC 50值为1.49μM，针对更具淀粉样性的V30 M TTR突变体的IC 50值为1.63μM 。这可以与批准的治疗药物他法米定（Tafamidis）相比，可以改善甲状腺素相关的淀粉样变性病。此外，通过利用计算机对接研究（其可以集中于甲状腺激素甲状腺素（T 4）结合位
• NOVEL 6-5 SYSTEM BICYCLIC HETEROCYCLIC DERIVATIVE AND ITS PHARMACEUTICAL UTILITY
  申请人：Asano Yukiyasu

  公开号：US20090176841A1

  公开（公告）日：2009-07-09

  An object of the present invention is to provide a medicament as a thyroid hormone receptor ligand which is sufficient in drug efficacy and safety, and has the excellent action as a drug. The present invention provides a compound represented by the following general formula (I) or a pharmaceutically acceptable salt thereof: [wherein [Chemical Formula 2] is a single bond or a double bond; A is —CH 2 — or —CO—; X, Y, and Z are each independently a nitrogen atom or a carbon atom; R 1 is a hydrogen atom or an aralkyl group; R 2 is an alkyl group or an aralkyl group, etc.; R 3 is a hydrogen atom or an alkyl group, etc.; R 4 is a hydrogen atom or an alkyl group; R 5 is a hydrogen atom, an alkyl group or a halo lower alkyl group, etc.; R 6 is a hydrogen atom or an alkyl group; R 7 is a hydrogen atom, etc.; R 8 is a hydrogen atom, or an alkyl group, etc.; and E is —NHCO-G-COR 12 , etc. (wherein G is a single bond or an alkylene group, and R 12 is a hydroxy group or an alkoxy group)].

  本发明的目的是提供一种作为甲状腺激素受体配体的药物，具有充分的药效和安全性，并具有优秀的药物作用。本发明提供了以下通式（I）所表示的化合物或其药学上可接受的盐：[其中[化学式2]是单键或双键；A是-CH2-或-CO-；X、Y和Z分别是氮原子或碳原子；R1是氢原子或芳基烷基；R2是烷基或芳基烷基等；R3是氢原子或烷基等；R4是氢原子或烷基；R5是氢原子、烷基或卤代低烷基等；R6是氢原子或烷基；R7是氢原子等；R8是氢原子或烷基等；E是-NHCO-G-COR12等（其中G是单键或烷基亚基，R12是羟基或烷氧基）]。
• A designed antagonist of the thyroid hormone receptor
  作者：Hikari A.I. Yoshihara、James W. Apriletti、John D. Baxter、Thomas S. Scanlan

  DOI：10.1016/s0960-894x(01)00521-2

  日期：2001.11

  We synthesized an analogue of the thyromimetic GC-1 bearing the same hydrophobic appendage as the estrogen receptor antagonist ICI-164,384. While having reduced affinity for the thyroid hormone receptors compared to GC-1, it behaves in a manner consistent with a competitive antagonist in a transactivation assay. (C) 2001 Elsevier Science Ltd. All rights reserved.
• THYROID HORMONE ANALOGUES AND METHODS FOR THEIR PREPARATION
  申请人：The Regents of the University of California

  公开号：EP1089968B1

  公开（公告）日：2005-04-20