4-(m-tolyl)tetrahydropyran-4-ol | 145127-34-0

• 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: 4-(m-tolyl)tetrahydropyran-4-ol
• 英文别名: 4-(3-Methylphenyl)oxan-4-ol
• CAS: 145127-34-0
• 化学式: C₁₂H₁₆O₂
• 分子量: 192.258
• InChiKey: FUEVYCNUMABXOJ-UHFFFAOYSA-N

物化性质

• 沸点：
  336.8±37.0 °C(Predicted)
• 密度：
  1.108±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  14
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 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：

  4-(m-tolyl)tetrahydropyran-4-ol 在 N-溴代丁二酰亚胺(NBS) 、 偶氮二异丁腈 、 potassium carbonate 作用下， 以 四氯化碳 、 N,N-二甲基甲酰胺 为溶剂， 反应 22.5h， 生成 L-702539
  参考文献：
  名称：

  Dioxabicyclooctanyl Naphthalenenitriles as Nonredox 5-Lipoxygenase Inhibitors:  Structure−Activity Relationship Study Directed toward the Improvement of Metabolic Stability

  摘要：

  Naphthalenic lignan lactone 3a (L-702,539), a potent and selective 5-lipoxygenase (5-LO) inhibitor, is extensively metabolized at two different sites: the tetrahydropyran and the lactone rings. Early knowledge of the metabolic pathways triggered and directed a structure-activity relationship study aimed toward the improvement of metabolic stability in this series. The best modifications discovered, i.e., replacement of the lactone ring by a nitrile group, replacement of the tetrahydropyran ring by a 6,8-dioxabicydo[3.2.1]octanyl moiety, and replacement of the pendant phenyl ring by a 3-furyl ring, were incorporated in a single molecule to produce inhibitor 9ac (L-708,780). Compound 9ac inhibits the oxidation of arachidonic acid to 5-hydroperoxy-eicosatetraenoic acid by 5-LO (IC50 = 190 nM) and the formation of leukotriene B-4 in human polymorphonuclear leukocytes (IC50 = 3 nM) as well as in human whole blood (IC50 = 150 nM). The good inhibitory profile shown by naphthalenenitrile 9ac is accompanied by an improved resistance to oxidative metabolism. In addition, 9ac is orally active in the functional model of antigen-induced bronchoconstriction in allergic squirrel monkeys (95% inhibition at 0.1 mg/kg).

  DOI：

  10.1021/jm960301c
• 作为产物：
  描述：

  四氢吡喃酮 、 3-溴甲基苯 在 正丁基锂 作用下， 以 四氢呋喃 为溶剂， 生成 4-(m-tolyl)tetrahydropyran-4-ol
  参考文献：
  名称：

  TRICYCLIC INHIBITORS OF 5-LIPOXYGENASE

  摘要：

  本文描述了含有这些化合物的化合物和药物组合物，这些化合物抑制5-脂氧合酶（5-LO）的活性。本文还描述了使用这种5-LO抑制剂的方法，单独或与其他化合物结合，用于治疗呼吸系统、心血管系统和其他依赖或介导白三烯的状况、疾病或紊乱。

  公开号：

  US20070173508A1

文献信息

• 5-LIPOXYGENASE-ACTIVATING PROTEIN (FLAP) INHIBITORS
  申请人：Hutchinson H. John

  公开号：US20070105866A1

  公开（公告）日：2007-05-10

  Described herein are compounds and pharmaceutical compositions containing such compounds, which modulate the activity of 5-lipoxygenase-activating protein (FLAP). Also described herein are methods of using such FLAP modulators, alone and in combination with other compounds, for treating respiratory, cardiovascular, and other leukotriene-dependent or leukotriene mediated conditions or diseases.

  本发明描述了调节5-脂氧合酶激活蛋白(FLAP)活性的化合物和含有该化合物的药物组合物。本发明还描述了单独使用和与其他化合物联合使用FLAP调节剂，用于治疗呼吸系统、心血管系统和其他白三烯依赖性或白三烯介导的状况或疾病。
• [EN] REDUCTION OF PRO-INFLAMMATORY HDL USING A LEUKOTRIENE INHIBITOR<br/>[FR] RÉDUCTION DE HDL PRO-INFLAMMATOIRE À L'AIDE D'UN INHIBITEUR DE LEUCOTRIÈNE
  申请人：AUTOIMMUNE PHARMA LLC

  公开号：WO2018152405A1

  公开（公告）日：2018-08-23

  A method involving the administration of a therapeutically effective amount of a leukotriene inhibitor, a pharmaceutically acceptable salt, a pharmaceutically acceptable N-oxide, a pharmaceutically active metabolite, a pharmaceutically acceptable prodrug, or pharmaceutically acceptable solvate thereof to a human for reducing a level of pro-inflammatory HDL in the human. Various examples of leukotriene inhibitors, including 3-[3-tert-butylsulfanyl-1-[4-(6-ethoxy-pyridin- 3-yl)-benzyl]-5-(5-methyl-pyridin-2-ylmethoxy)-1H-indol-2-yl]-2, 2-dimethyl-propionic acid, are disclosed for administration for the reduction of pro-inflammatory HDL in a human. Reduction of pro-inflammatory HDL by the leukotriene inhibitor may include conversion of at least a portion of pro-inflammatory HDL to anti-inflammatory HDL.

  一种方法，涉及给人类施用治疗有效量的白细胞三烯抑制剂、药物可接受的盐、药物可接受的N-氧化物、药物活性代谢物、药物可接受的的前药或其药物可接受的溶剂化物，以降低人类中的前炎症高密度脂蛋白(HDL)水平。公开了各种白细胞三烯抑制剂，包括3-[3-叔丁基硫基-1-[4-(6-乙氧基-吡啶-3-基)-苄基]-5-(5-甲基-吡啶-2-基甲氧基)-1H-吲哚-2-基]-2,2-二甲基丙酸，用于施用以降低人类中的前炎症HDL。通过白细胞三烯抑制剂降低前炎症HDL可能包括将至少部分前炎症HDL转化为抗炎症HDL。
• New preparation of N(1)- and N(2)- alkylated tetrazoles via displacement of activated alcohols
  作者：Réjean Fortin、Christian Brochu

  DOI：10.1016/0040-4039(94)88358-0

  日期：1994.12

  A facile and convenient synthesis of N(1)- and N(2)-alkyltetrazoles is described. Tetrazole in the presence of zinc triflate reacts smoothly with activated alcohols to give the corresponding alkyltetrazole in high yield.

  描述了一种简便的N（1）-和N（2）-烷基四唑的合成方法。在三氟甲磺酸锌存在下，四唑与活化的醇平稳反应，以高收率得到相应的烷基四唑。
• 5-Lipoxygenase-Activating Protein (FLAP) Inhibitors
  申请人：Hutchinson John H.

  公开号：US20090221574A1

  公开（公告）日：2009-09-03

  Described herein are compounds and pharmaceutical compositions containing such compounds, which modulate the activity of 5-lipoxygenase-activating protein (FLAP). Also described herein are methods of using such FLAP modulators, alone and in combination with other compounds, for treating respiratory, cardiovascular, and other leukotriene-dependent or leukotriene mediated conditions or diseases.

  本文描述了包含这些化合物的药物组合物，这些化合物调节5-脂氧合酶活化蛋白（FLAP）的活性。本文还描述了使用这样的FLAP调节剂的方法，单独或与其他化合物结合，用于治疗呼吸系统、心血管系统和其他依赖于白三烯或介导白三烯的疾病或病症。
• 5-LIPOXGENASE-ACTIVATING PROTEIN (FLAP) INHIBITORS
  申请人：Panmira Pharmaceuticals, LLC

  公开号：US20140018394A1

  公开（公告）日：2014-01-16

  Described herein are compounds and pharmaceutical compositions containing such compounds, which modulate the activity of 5-lipoxygenase-activating protein (FLAP). Also described herein are methods of using such FLAP modulators, alone and in combination with other compounds, for treating respiratory, cardiovascular, and other leukotriene-dependent or leukotriene mediated conditions or diseases.

  本文描述了一些化合物和含有这些化合物的药物组合物，可调节5-脂氧合酶激活蛋白（FLAP）的活性。本文还描述了使用这种FLAP调节剂的方法，单独或与其他化合物组合，用于治疗呼吸系统、心血管系统和其他依赖或介导白三烯的疾病或病情。