4-hydroxybenzyl 2-methoxyethyl ether | 115319-73-8

• 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-hydroxybenzyl 2-methoxyethyl ether
• 英文别名: 4-(2-methoxyethoxymethyl)phenol；2-(4-hydroxybenzyloxy)-1-methoxyethane
• CAS: 115319-73-8
• 化学式: C₁₀H₁₄O₃
• 分子量: 182.219
• InChiKey: ROLLYPTWGVIGLQ-UHFFFAOYSA-N

物化性质

• 沸点：
  283.1±20.0 °C(Predicted)
• 密度：
  1.094±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  13
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  38.7
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-hydroxybenzyl 2-methoxyethyl ether 在 potassium tert-butylate 、 caesium carbonate 作用下， 以 四氢呋喃 为溶剂， 反应 3.5h， 生成 Methyl 4-[4-(2-methoxyethoxymethyl)phenoxy]thieno[2,3-c]pyridine-2-carboxylate
  参考文献：
  名称：

  Selective Inhibition of ICAM-1 and E-Selectin Expression in Human Endothelial Cells. 2. Aryl Modifications of 4-(Aryloxy)thieno[2,3-c]pyridines with Fine-Tuning at C-2 Carbamides

  摘要：

  The elevated expression of cell adhesion molecules (CAMs) on the lumenal surface of vascular endothelial cells is a critical early event in the complex inflammatory process. The adhesive interactions of these CAMs that include E-selectin, ICAM-1, and VCAM-1 with their counterreceptors on leukocytes, such as integrins of the alpha (L)beta (2) family, result in migration of the leukocytes to the site of inflammation and cause tissue injury. Pharmaceutical agents that could suppress the induced expression of one or more of these cell adhesion molecules would provide a novel mechanism to attenuate the inflammatory responses associated with chronic inflammatory diseases. A-205804 (1), a potent and selective inhibitor of the induced expression of E-selectin and ICAM-1 over VCAM-1, was further modified with emphasis at the C-4 and C-2 positions to identify a more potent drug candidate with a good pharmacokinetic profile and physical properties. Replacement of the C-4 sulfur linkage in I with an oxygen atom eliminated one of the two major metabolites for this lead molecule. The para-position of the 4-phenoxy group of the thieno[2,3-c]pyridine lead is found to be very critical for a higher in vitro potency and selectivity of E-selectin and ICAM-1 over VCAM-1 expression. This position is presumably close to the solvent-accessible region of the target protein-inhibitor complex. An attempt to install a water-solubilizing group at the para-position of the phenoxy group to increase the aqueous solubility of this lead series through various linkages failed to provide an ideal inhibitor. Only small substituents such as fluorine are tolerated at the meta- and ortho-positions of the 4-phenoxy to retain a good in vitro potency. Bromo, trifluoromethyl, pyrazol-1-yl, and imidazol-1-yl are among the better substituents at the para-position. With fine-tuning at the C-2 position we discovered a series of very potent (IC50 < 5 nM for ICAM-1) and selective (> 200-fold vs VCAM-1) inhibitors with a good pharmacokinetic profile. Demonstrated efficacy in a rat rheumatoid arthritis model and in a mice asthma model with selected compounds is also reported.

  DOI：

  10.1021/jm0101702
• 作为产物：
  描述：

  乙二醇甲醚 、 对羟基苯甲醇 在 ytterbium(III) triflate 作用下， 以 乙腈 为溶剂， 反应 5.0h， 以65%的产率得到4-hydroxybenzyl 2-methoxyethyl ether
  参考文献：
  名称：

  Rare Earth Metal Trifluoromethanesulfonates Catalyzed Benzyl-Etherification.

  摘要：

  稀土金属三氟甲磺酸盐[稀土金属三氟甲磺酸酯，RE(OTf)3]被发现是苄基醚化的有效催化剂。在微量RE(OTf)3的催化作用下，苄醇与脂肪醇顺利进行缩合反应，生成苄基醚。苄醇与硫醇之间的缩合反应也能进行，并以良好产率得到硫醚。在这些反应中，RE(OTf)3在反应结束后易于回收，且可重复使用而不会损失活性。

  DOI：

  10.1248/cpb.50.380

文献信息

• Heterocyclic derivatives
  申请人：Zeneca Limited

  公开号：US05919793A1

  公开（公告）日：1999-07-06

  Compounds of formula (I) wherein R.sup.1 is hydrogen or hydroxy; R.sup.2 is hydrogen; or R.sup.1 and R.sup.2 are joined together so that CR.sup.1 14 CR.sup.2 is a double bond; X is selected from --Ch.sub.2 CH.sub.2 --, --C.dbd.CH--, --C.tbd.C--, --CH.sub.2 O--, --OCH.sub.2, CH.sub.2 NH--, --NHCH.sub.2 --, --CH.sub.2 CO--, --COCH.sub.2 --, --CH.sub.2 S(O).sub.n -- and --S(O).sub.n CH.sub.2 -- (wherein n is 0, 1 or 2); Ar is phenyl which bears one or more substituents independently selected from the groups (1-6C)alkyl, (2-6C)alkenyl, (2-6C)alkynyl, (1-6C)alkoxy, (1-6C)alkoxycarbonyl, (1-6C)alkoxycarbonyl(1-6C)alkyl, (1-6C)alkoxy(1-6C)alkyl, (1-6C)alkylamino, di-\x9b(1-6C)alkyl!amino, carbamoyl, (1-6C) alkylcarbamoyl, di-\x9b(1-6C)alkyl!carbamoyl, (1-6C)alkenyl and oxime derivatives thereof and O--(1-6C)alkyl ethers of said oximes (1-6C)alkylthio, (1-6C)alkylsulphinyl and (1-6C)alkylsulphonyl when substituted by one or more groups selected from (1-6C)alkoxycarbonyl, (1-6C)alkanoyl and oxime derivatives thereof and O-(1-6C)alkyl ethers of said oxime derivatives, (1-6C)alkanoylamimo, (1-6C)alkanoyloxy, (1-6C)alkanoyloxy(1-6)alkyl, carbamoyl, N-(1-6C)alkylcarbamoyl, N,N-di\x9b(1-6C)alkyl!carbamoyl, amino, (1-6C)alkylamino, di-\x9b(1-6C)alkyl!amino, (1-6C)alkoxy, (2-6C)alkenyloxy, (1-6C)alkylthio, (1-6C)alkylsulphinyl, (1-6C)alkylsulphonyl, halogeno(1-6C)alkyl (2-6C)alkenyl, (2-6C)alkynyl, phenyl, phenoxy, cyano, nitro, hydroxy and carboxy; and wherein Ar may bear further substituents; and their pharmaceutically acceptable salts inhibit squalene synthese and are hence useful in lowering cholesterol levels in blood plasma Processes for preparing compounds of formula (I) are also referred to as well as pharmaceutical compositions containing them and their use in medicine.

  式(I)中的化合物，其中R.sup.1是氢或羟基；R.sup.2是氢；或R.sup.1和R.sup.2结合在一起，使得CR.sup.1 14 CR.sup.2是一个双键；X从--Ch.sub.2 CH.sub.2 --，--C.dbd.CH--，--C.tbd.C--，--CH.sub.2 O--，--OCH.sub.2，CH.sub.2 NH--，--NHCH.sub.2 --，--CH.sub.2 CO--，--COCH.sub.2 --，--CH.sub.2 S(O).sub.n --和--S(O).sub.n CH.sub.2 --中选择（其中n为0、1或2）；Ar是苯基，其上独立选择自基团（1-6C）烷基，（2-6C）烯基，（2-6C）炔基，（1-6C）烷氧基，（1-6C）烷氧羰基，（1-6C）烷氧羰基（1-6C）烷基，（1-6C）烷氧基（1-6C）烷基，（1-6C）烷基氨基，二-\x9b（1-6C）烷基！氨基，氨基甲酰基，（1-6C）烷基甲酰基，二-\x9b（1-6C）烷基！甲酰基，（1-6C）烯基和其氧肟衍生物和所述氧肟的O-（1-6C）烷基醚（1-6C）烷硫基，（1-6C）烷磺基和（1-6C）烷磺基，当被一个或多个基团选择时，从（1-6C）烷氧羰基，（1-6C）烷酰基和其氧肟衍生物和所述氧肟衍生物的O-（1-6C）烷基醚，（1-6C）烷酰胺基，（1-6C）烷酰氧基，（1-6C）烷酰氧基（1-6）烷基，氨基甲酰基，N-（1-6C）烷基甲酰基，N，N-二\x9b（1-6C）烷基！甲酰基，氨基，（1-6C）烷基氨基，二-\x9b（1-6C）烷基！氨基，（1-6C）烷氧基，（2-6C）烯氧基，（1-6C）烷硫基，（1-6C）烷磺基，（1-6C）烷磺基，卤代（1-6C）烷基（2-6C）烯基，（2-6C）炔基，苯基，苯氧基，氰基，硝基，羟基和羧基；其中Ar可能带有进一步的取代基；它们的药学上可接受的盐抑制角鲨烯合成，因此在降低血浆胆固醇水平方面有用。制备式(I)化合物的方法也被提及，以及含有它们的药物组合物及其在医学中的用途。
• Cell adhesion-inhibiting antiinflammatory compounds
  申请人：Abbott Laboratories

  公开号：US06232320B1

  公开（公告）日：2001-05-15

  Compounds having Formula I are useful for treating inflammation. Also disclosed are pharmaceutical compositions comprising compounds of Formula I, and methods of inhibiting/treating inflammatory diseases in a mammal.

  具有I式化学式的化合物对于治疗炎症是有用的。还公开了包含I式化合物的药物组合物，以及在哺乳动物中抑制/治疗炎症性疾病的方法。
• On the metalation of phenolic compounds: Ready access to highly substituted phenols.
  作者：Antonio Costa、José M. Saá

  DOI：10.1016/s0040-4039(00)96778-9

  日期：1987.1

  studied. Those substrates possesing an electron-withdrawing group in a 1,3 relationship with the coordinating (-CH2OMe) group underwent regioselective metalation by the action of n-BuLi/THF. Highly substituted phenols can thus be readly prepared.

  已经研究了几种对羟基苄基甲基醚的直接金属化。那些具有与配位基团（-CH 2 OMe）成1,3关系的吸电子基团的底物在n-BuLi / THF的作用下进行了区域选择性金属化。因此可以容易地制备高度取代的酚。
• Metalation of phenols. Synthesis of benzoquinones by the oxidative degradation approach
  作者：Jose M. Saa、Antonia Llobera、Angel Garcia-Raso、Antonio Costa、Pedro M. Deya

  DOI：10.1021/jo00253a019

  日期：1988.9
• HETEROCYCLIC DERIVATIVES
  申请人：ZENECA LIMITED

  公开号：EP0696284A1

  公开（公告）日：1996-02-14