3-[1-甲氧基-1-(2-噻唑)丙基]苯酚 | 129424-07-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 3-[1-甲氧基-1-(2-噻唑)丙基]苯酚
• 英文名称: 3-<1-methoxy-1-(thiazol-2-yl)propyl>phenol
• 英文别名: 1-(3-hydroxyphenyl)-1-(thiazol-2-yl)propyl methyl ether；2-[1-(3-hydroxyphenyl)-1-methoxypropyl]thiazole；3-[1-Methoxy-1-(1,3-thiazol-2-yl)propyl]phenol
• CAS: 129424-07-3
• 化学式: C₁₃H₁₅NO₂S
• 分子量: 249.334
• InChiKey: XUJSTHPLYZTDJL-UHFFFAOYSA-N

物化性质

• 沸点：
  386.2±37.0 °C(Predicted)
• 密度：
  1.206±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  17
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  70.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3-[1-甲氧基-1-(2-噻唑)丙基]苯酚 在 1,1'-双(二苯基膦)二茂铁 、 palladium diacetate 、 2,6-二叔丁基吡啶 、 三乙胺 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 18.67h， 生成 methyl 3-<1-methoxy-1-(thiazol-2-yl)propyl>benzoate
  参考文献：
  名称：

  Naphthalenic Lignan Lactones as Selective, Nonredox 5-Lipoxygenase Inhibitors. Synthesis and Biological Activity of (Methoxyalkyl)thiazole and Methoxytetrahydropyran Hybrids

  摘要：

  Combinations of structural elements found in (methoxyalkyl)thiazole 1a and methoxytetrahydropyran 2a with a naphthalenic lignan lactone produce the potent 5-lipoxygenase (5-LO) inhibitors 3 and 4. While the nature of link Y-Z has a major effect on the in vitro activity of compounds 1 and 2, inhibitors 3 and 4 retain their potencies with either an oxymethylene (Y = O, Z = CH2) or a methyleneoxy (Y = CH2, Z = O) link. Compound 4b inhibits the oxidation of arachidonic acid to 5-hydroperoxyeicosatetraenoic acid by 5-LO (IC50 = 14 nM) and the formation of leukotriene Bq in human polymorphonuclear leukocytes (IC50 = 1.5 nM) as well as in human whole blood (IC50 = 50 nM). Compound 4b is a selective 5-LO inhibitor showing no significant inhibition of human 15-lipoxygenase or porcine 12-lipoxygenase or binding to human 5-lipoxygenase-activating protein up to 10 mu M and inhibits leukotriene biosynthesis by a direct, nonredox interaction with 5-LO. Compound 15, the open form of lactone 4b, is well absorbed in the rat and is transformed into the active species 4b. In addition, 15 is orally active in the rat pleurisy model (ED(50) = 0.6 mg/kg) and in the functional model of antigen-induced bronchoconstriction in allergic squirrel monkeys (95% inhibition at 0.3 mg/kg).

  DOI：

  10.1021/jm00030a010
• 作为产物：
  描述：

  1-hydroxy-1-<3-<(tert-butyldimethylsilyl)oxy>phenyl>-1-(thiazol-2-yl)propane 在 四丁基氟化铵 、 sodium hydride 作用下， 以 四氢呋喃 为溶剂， 反应 4.0h， 生成 3-[1-甲氧基-1-(2-噻唑)丙基]苯酚
  参考文献：
  名称：

  （甲氧基烷基）噻唑类：一系列新的有效，选择性和口服活性的5-脂氧合酶抑制剂，显示出高对映选择性。

  摘要：

  （甲氧基烷基）噻唑是新颖的5-脂氧合酶（5-LPO）抑制剂，既不是氧化还原剂也不是铁螯合剂。考虑到酶活性位点的假设模型导致了该系列，该系列以1- [3-（萘-2-基甲氧基）苯基] -1-（噻唑-2-基）丙基甲基醚（2d，ICI211965）为例）。2d抑制无细胞豚鼠5-LPO活性，无血浆小鼠巨噬细胞中的LTC4合成以及大鼠和人类血液中的LTB4合成（IC50分别为0.1 microM，8 nM，0.5 microM和0.4 microM），但不抑制在巨噬细胞中合成浓度高达50 microM，在血液中合成浓度高达100 microM的环氧合酶产物。2d在大鼠中具有口服活性（给药后1小时内在血液中离体ED50 10 mg / kg）。SAR研究表明，高体外效力需要甲氧基，噻唑基，和萘基，并且主要取决于取代方式。（甲氧基烷基）噻唑是手性的。1-甲氧基-6-（萘-2-基甲氧基）-1-（噻唑-2-基

  DOI：

  10.1021/jm00111a038

文献信息

• 5-lipoxygenase inhibitory thiazoles
  申请人：ICI Pharma

  公开号：US05089513A1

  公开（公告）日：1992-02-18

  The invention concerns a thiazole of the formula I, ##STR1## wherein Ar.sup.1 is optionally substituted aryl of up to 10 carbon atoms; A is a direct link to X, or is (1-6C)alkylene, (3-6C)alkenylene, (3-6C)alkynylene or cyclo(3-6C)alkylene; X is oxy, thio, sulphinyl, sulphonyl or imino; Ar.sup.2 is optionally substituted phenylene, or a 6-membered heterocyclene moiety containing up to three nitrogen atoms; R.sup.1 is hydrogen, (1-6C)alkyl, (2-6C)alkenyl, (2-6C)alkynyl or substituted (1-4C)alkyl; R.sup.2 is hydrogen, (1-6C)alkyl, (3-6C)alkenyl, (3-6C)alkynyl, substituted (1-4C)alkyl or (2-6C)alkanoyl; Q is optionally substituted thiazolyl; or a pharmaceutically-acceptable salt thereof. The invention also concerns processes for the manufacture of a thiazole of the formula I, or a pharmaceutically-acceptable salt thereof, and pharmaceutical compositions containing said thiazole.

  该发明涉及一种式I的噻唑化合物，其中Ar.sup.1是最多含有10个碳原子的可选择取代的芳基；A是直接连接到X，或者是(1-6C)烷基，(3-6C)烯基，(3-6C)炔基或环(3-6C)烷基；X是氧，硫，亚硫基，磺酰基或亚胺基；Ar.sup.2是可选择取代的苯基，或者含有最多三个氮原子的6元杂环基；R.sup.1是氢，(1-6C)烷基，(2-6C)烯基，(2-6C)炔基或取代的(1-4C)烷基；R.sup.2是氢，(1-6C)烷基，(3-6C)烯基，(3-6C)炔基，取代的(1-4C)烷基或(2-6C)烷酰基；Q是可选择取代的噻唑基；或其药学上可接受的盐。该发明还涉及制备式I的噻唑化合物或其药学上可接受的盐的方法，以及含有该噻唑化合物的药物组合物。
• Heterocyclic thiazole derivatives and pharmaceutical compositions
  申请人：Imperial Chemical Industries PLC

  公开号：US05089495A1

  公开（公告）日：1992-02-18

  The invention concerns a thiazole of the formula I, ##STR1## wherein Q.sup.1 is an optionally substituted 6-membered monocyclic or 10-membered bicyclic heterocyclic moiety containing one or two nitrogen atoms; X is oxy, thio, sulphinyl, sulphonyl or imino; Ar is phenylene which may optionally bear one or two substituents, or Ar is an optionally substituted 6-membered heterocyclene moiety continuing up to three nitrogen atoms; R.sup.1 is hydrogen, (1-6C)alkyl, (2-6C)alkenyl, (2-6C)alkynyl or substituted (1-4C)alkyl; R.sup.2 is hydrogen, (1-6C)alkyl, (3-6C)alkenyl, (3-6C)alkynyl or substituted (1-4C)alkyl or R.sup.2 is optionally substituted benzoyl; and Q.sup.2 is optionally substituted thiazolyl; or a pharmaceutically-acceptable salt thereof. The invention also concerns processes for the manufacture of a thiazole of the formula I and pharmaceutical compositions containing said thiazole.

  这项发明涉及一种公式I的噻唑化合物，其中Q.sup.1是一个可选择取代的含有一个或两个氮原子的6元单环或10元双环杂环基团；X是氧、硫、亚硫基、磺酰基或亚胺基；Ar是苯基，可以选择携带一个或两个取代基，或者Ar是一个可选择取代的含有最多三个氮原子的6元杂环基团；R.sup.1是氢、(1-6C)烷基、(2-6C)烯基、(2-6C)炔基或取代的(1-4C)烷基；R.sup.2是氢、(1-6C)烷基、(3-6C)烯基、(3-6C)炔基或取代的(1-4C)烷基，或者R.sup.2是可选择取代的苯甲酰基；Q.sup.2是可选择取代的噻唑基；或其药学上可接受的盐。该发明还涉及一种制备公式I的噻唑化合物的方法和含有该噻唑化合物的药物组合物。
• Thiazole derivatives having a 5-lipoxygenase-inhibiting activity
  申请人：IMPERIAL CHEMICAL INDUSTRIES PLC

  公开号：EP0351194B1

  公开（公告）日：1994-06-15
• Heterocyclic derivatives
  申请人：IMPERIAL CHEMICAL INDUSTRIES PLC

  公开号：EP0381375B1

  公开（公告）日：1992-11-11
• Ducharme Yves, Brideau Christine, Dube Daniel, Chan Chi-Chung, Falgueyret+, J. Med. Chem, 37 (1994) N 4, S 512-518
  作者：Ducharme Yves, Brideau Christine, Dube Daniel, Chan Chi-Chung, Falgueyret+

  DOI：——

  日期：——