3-[1,1-bis(methylethyl)-2-methyl-1-silapropoxy]phenol | 474658-51-0

• 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: 3-[1,1-bis(methylethyl)-2-methyl-1-silapropoxy]phenol
• 英文别名: 3-(triisopropylsilyloxy)phenol；3-tri(propan-2-yl)silyloxyphenol
• CAS: 474658-51-0
• 化学式: C₁₅H₂₆O₂Si
• 分子量: 266.456
• InChiKey: HYIXVWKAFNAMOX-UHFFFAOYSA-N

物化性质

• 沸点：
  315.2±25.0 °C(Predicted)
• 密度：
  0.948±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.95
• 重原子数：
  18
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  29.5
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  3-[1,1-bis(methylethyl)-2-methyl-1-silapropoxy]phenol 在 硫酸 、 四丁基氟化铵 、 三苯基膦 、 偶氮二甲酸二乙酯 作用下， 以 四氢呋喃 为溶剂， 反应 3.5h， 生成 ethyl 3-(6-{2-[6-(methylamino)-2-pyridyl]ethoxy}benzo[b]furan-3-yl)propanoate
  参考文献：
  名称：

  Design, Synthesis, and Biological Evaluation of Novel Potent and Selective α_vβ₃/α_vβ₅ Integrin Dual Inhibitors with Improved Bioavailability. Selection of the Molecular Core

  摘要：

  A novel series of potent and selective alpha(v)beta(3)/alpha(v)beta(5) dual inhibitors was designed, synthesized, and evaluated against several integrins. These compounds were synthesized through a Mitsunobu reaction between the guanidinium mimetics and the corresponding central templates. Guanidinium mimetics with enhaced rigidity (i.e., (2-pyridylamino)propoxy versus the 2-(6-methylamino-2-pyridyl)ethoxy) led to improved activity toward alpha(v)beta(3). Exemplary oral bioavailability in mice was achieved using the indole central scaffold. Although, oral bioavailability was maintained when the indole molecular core was replace with the bioisosteric benzofuran or benzothiophene ring systems, it was found to not significantly impact the integrin activity or selectivity. However, the indole series displayed the best in vivo pharmacokinetic properties. Thus, the indole series was selected for further structure-activity relationships to obtain more potent alpha(v)beta(3)/alpha(v)beta(5) dual antagonist with improved oral bioavailability.

  DOI：

  10.1021/jm049725u
• 作为产物：
  描述：

  1,3-苯二醇单乙酸酯 在 sodium hydroxide 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 为溶剂， 反应 0.17h， 生成 3-[1,1-bis(methylethyl)-2-methyl-1-silapropoxy]phenol
  参考文献：
  名称：

  Design, Synthesis, and Biological Evaluation of Novel Potent and Selective α_vβ₃/α_vβ₅ Integrin Dual Inhibitors with Improved Bioavailability. Selection of the Molecular Core

  摘要：

  A novel series of potent and selective alpha(v)beta(3)/alpha(v)beta(5) dual inhibitors was designed, synthesized, and evaluated against several integrins. These compounds were synthesized through a Mitsunobu reaction between the guanidinium mimetics and the corresponding central templates. Guanidinium mimetics with enhaced rigidity (i.e., (2-pyridylamino)propoxy versus the 2-(6-methylamino-2-pyridyl)ethoxy) led to improved activity toward alpha(v)beta(3). Exemplary oral bioavailability in mice was achieved using the indole central scaffold. Although, oral bioavailability was maintained when the indole molecular core was replace with the bioisosteric benzofuran or benzothiophene ring systems, it was found to not significantly impact the integrin activity or selectivity. However, the indole series displayed the best in vivo pharmacokinetic properties. Thus, the indole series was selected for further structure-activity relationships to obtain more potent alpha(v)beta(3)/alpha(v)beta(5) dual antagonist with improved oral bioavailability.

  DOI：

  10.1021/jm049725u

文献信息

• Facile Synthesis of Multisubstituted Benzo[<i>b</i>]furans via 2,3-Disubstituted 6,7-Furanobenzynes Generated from <i>ortho</i>-Iodoaryl Triflate-type Precursors
  作者：Takamoto Morita、Yoshitake Nishiyama、Suguru Yoshida、Takamitsu Hosoya

  DOI：10.1246/cl.160951

  日期：2017.1.5

  a highly regioselective manner. Since a variety of precursors were easily synthesizable from readily available 2,3-disubstituted 6-hydroxybenzofurans, this method enabled facile synthesis of a wide range of multisubstituted benzofurans, including π-extended molecules.

  使用甲硅烷基甲基格氏试剂作为活化剂，从邻碘芳基三氟甲磺酸酯型前体有效生成 2,3-二取代的 6,7-呋喃苯乙炔。6,7-呋喃苯乙炔和不对称亲芳体之间的反应以高度区域选择性的方式进行。由于各种前体很容易从容易获得的 2,3-二取代 6-羟基苯并呋喃合成，该方法能够轻松合成多种多取代苯并呋喃，包括 π 扩展分子。
• Substituted benzofurans and benzothiophenes, methods of making and methods of use as integrin antagonists
  申请人：3-Dimensional Pharmaceuticals, Inc.

  公开号：US20030018064A1

  公开（公告）日：2003-01-23

  The present invention relates to novel substituted benzofurans and benzothiophenes compounds that are antagonists of alpha V (&agr;v) integrins, for example &agr; v &bgr; 3 and &agr; v &bgr; 5 integrins, their pharmaceutically acceptable salts, and pharmaceutical compositions thereof. The compounds may be used in the treatment of pathological conditions mediated by &agr; v &bgr; 3 and &agr; v &bgr; 5 integrins, including such conditions as tumor growth, metastasis, restenosis, osteoporosis, inflammation, macular degeneration, diabetic retinopathy, and rheumatoid arthritis. The compounds have the general formula I: 1 where R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 10 , R 11 , R 12 , R 13 , R 14 , m, n, i, j and k are defined herein.

  本发明涉及新型取代苯并呋喃和苯并噻吩化合物，它们是αV（αv）整合素的拮抗剂，例如αvβ3和αvβ5整合素，它们的药学上可接受的盐以及其制药组合物。这些化合物可用于治疗由αvβ3和αvβ5整合素介导的病理条件，包括肿瘤生长、转移、再狭窄、骨质疏松、炎症、黄斑变性、糖尿病视网膜病变和类风湿性关节炎等疾病。这些化合物具有通式I：其中R1、R2、R3、R4、R5、R6、R7、R8、R9、R10、R11、R12、R13、R14、m、n、i、j和k在此定义。
• Synthesis of Unsymmetrical <i>o</i>-Biphenols and <i>o</i>-Binaphthols via Silicon-Tethered Pd-Catalyzed C−H Arylation
  作者：Chunhui Huang、Vladimir Gevorgyan

  DOI：10.1021/ol100924n

  日期：2010.5.21

  A mild, practical, and efficient method for the synthesis of unsymmetrical o-biphenols (including o-phenol-naphthols and o-binaphthols) has been developed. Unsymmetrical bis-aryloxy silanes, which were readily prepared in a semi-one-pot fashion, underwent the Pd-catalyzed intramolecular arylation followed by a routine TBAF desilylation step to furnish valuable unsymmetrical biphenols without necessity of isolation of seven-membered intermediates. The excellent functional group tolerance allows for synthesis of a variety of functionalized o-biphenols and o-binaphthols from easily available staring materials.