6-(1-Propan-2-ylpiperidin-4-yl)oxynaphthalene-2-carboxylic acid | 871208-64-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: 6-(1-Propan-2-ylpiperidin-4-yl)oxynaphthalene-2-carboxylic acid
• CAS: 871208-64-9
• 化学式: C₁₉H₂₃NO₃
• 分子量: 313.397
• InChiKey: MYNWOUJCXVIJJM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  23
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  49.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-甲氧基哌啶 、 6-(1-Propan-2-ylpiperidin-4-yl)oxynaphthalene-2-carboxylic acid 在 N,N'-羰基二咪唑 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 [6-(1-isopropyl-piperidin-4-yloxy)-quinolin-2-yl]-(4-methoxy-piperidin-1-yl)-methanone
  参考文献：
  名称：

  Selective naphthalene H3 receptor inverse agonists with reduced potential to induce phospholipidosis and their quinoline analogs

  摘要：

  We reported earlier the refinement of our initial. ve-point pharmacophore model for the Histamine 3 receptor (H3R), with a new acceptor feature important for binding and selectivity against the other histamine receptor subtypes 1, 2 and 4. This approach was validated with a new series of H3R inverse agonists: the naphthalene series. In this Letter, we describe our efforts to overcome the phospholipidosis flag identified with our initial lead compound (1a). During the optimization process, we monitored the potency of our molecules toward the H-3 receptor, their selectivity against H1R, H2R and H4R, as well as some key molecular properties that may influence phospholipidosis.Encouraged by the promising pro. le of the naphthalene series, we used our deeper understanding of the H3R pharmacophore model to lead us towards the quinoline series. This series is perceived to have intrinsic advantages with respect to its amphiphilic vector. (C) 2009 Published by Elsevier Ltd.

  DOI：

  10.1016/j.bmcl.2009.03.100
• 作为产物：
  描述：

  在 盐酸 作用下， 以 1,4-二氧六环 、 水 为溶剂， 生成 6-(1-Propan-2-ylpiperidin-4-yl)oxynaphthalene-2-carboxylic acid
  参考文献：
  名称：

  Selective naphthalene H3 receptor inverse agonists with reduced potential to induce phospholipidosis and their quinoline analogs

  摘要：

  We reported earlier the refinement of our initial. ve-point pharmacophore model for the Histamine 3 receptor (H3R), with a new acceptor feature important for binding and selectivity against the other histamine receptor subtypes 1, 2 and 4. This approach was validated with a new series of H3R inverse agonists: the naphthalene series. In this Letter, we describe our efforts to overcome the phospholipidosis flag identified with our initial lead compound (1a). During the optimization process, we monitored the potency of our molecules toward the H-3 receptor, their selectivity against H1R, H2R and H4R, as well as some key molecular properties that may influence phospholipidosis.Encouraged by the promising pro. le of the naphthalene series, we used our deeper understanding of the H3R pharmacophore model to lead us towards the quinoline series. This series is perceived to have intrinsic advantages with respect to its amphiphilic vector. (C) 2009 Published by Elsevier Ltd.

  DOI：

  10.1016/j.bmcl.2009.03.100

文献信息

• [EN] NAPHTHALINE DERIVATIVES USEFUL AS HISTAMINE-3-RECEPTOR LIGANDS<br/>[FR] DERIVES DE LA NAPHTALINE UTILISES COMME LIGANDS DU RECEPTEUR 3 DE L'HISTAMINE
  申请人：HOFFMANN LA ROCHE

  公开号：WO2005117865A1

  公开（公告）日：2005-12-15

  The present invention relates to compounds of formula (I) wherein A, R1 and R2 are as defined in the description and claims, and pharmaceutically acceptable salts thereof, to the preparation of such compounds and pharmaceutical compositions containing them. The compounds are useful for the treatment and/or prevention of diseases which are associated with the modulation of H3 receptors.

  本发明涉及式（I）的化合物，其中A，R1和R2如描述和索赔中所定义，以及其药学上可接受的盐，以及制备这些化合物和含有它们的药物组合物。这些化合物可用于治疗和/或预防与H3受体调节相关的疾病。
• Naphthaline derivatives as H3 inverse agonists
  申请人：McArthur Gatti Silvia

  公开号：US20060009449A1

  公开（公告）日：2006-01-12

  The present invention relates to compounds of formula I: and pharmaceutically acceptable salts thereof, to the preparation of such compounds and pharmaceutical compositions containing them. The compounds are useful for the treatment and/or prevention of diseases which are associated with the modulation of H3 receptors.

  本发明涉及公式I的化合物及其药学上可接受的盐，以及制备这些化合物和含有它们的制药组合物。这些化合物用于治疗和/或预防与H3受体调节相关的疾病。
• NAPHTHALINE DERIVATIVES USEFUL AS HISTAMINE-3-RECEPTOR LIGANDS
  申请人：F.HOFFMANN-LA ROCHE AG

  公开号：EP1755593A1

  公开（公告）日：2007-02-28
• NAPHTHALENE DERIVATIVES USEFUL AS HISTAMINE-3-RECEPTOR LIGANDS
  申请人：F.HOFFMANN-LA ROCHE AG

  公开号：EP1755593B1

  公开（公告）日：2008-01-16
• US7259158B2
  申请人：——

  公开号：US7259158B2

  公开（公告）日：2007-08-21