4-(10,11-dihydro-5H-dibenzocyclohepten-5-yloxy)piperidine | 1094-03-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 二苯并环庚烯
• 英文名称: 4-(10,11-dihydro-5H-dibenzocyclohepten-5-yloxy)piperidine
• 英文别名: 4-(2-Tricyclo[9.4.0.03,8]pentadeca-1(15),3,5,7,11,13-hexaenyloxy)piperidine
• CAS: 1094-03-7
• 化学式: C₂₀H₂₃NO
• 分子量: 293.409
• InChiKey: ICSGHZYFNMJUDZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  22
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  21.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  4-(10,11-dihydro-5H-dibenzocyclohepten-5-yloxy)piperidine 在 sodium hydroxide 、 sodium carbonate 、 sodium iodide 作用下， 以 乙醇 、 水 、 丙酮 为溶剂， 反应 3.0h， 生成 (R)-2-Benzyloxycarbonylamino-3-[4-(10,11-dihydro-5H-dibenzo[a,d]-cyclohepten-5-yloxy)piperidin-1-yl]propionic acid
  参考文献：
  名称：

  Synthesis and pharmacological evaluation of some amino-acid-containing cyproheptadine derivatives as dual antagonists of histamine H1- and leukotriene D4-receptors

  摘要：

  A novel series of cyproheptadine derivatives, in which an amino acid or a dipeptide moiety was introduced at the piperidine nitrogen, have been synthesized. The amino acid and dipeptide moieties were taken as part of leukotriene D-4 (LTD(4)) pharmacophore. This modification reduced the H-1-antihistamine activity (100-1000-fold) but elevated the anti-LTD(4) activity (10-100-fold) of the compounds, as compared with cyproheptadine. As a result, some of the new compounds, especially the alpha-amino-propionic acid derivatives 4, are well-balanced dual antagonists of histamine and LTD(4) with both activities at micromolar range. Radioligand binding studies have confirmed that the new compounds, but not cyproheptadine for LTD(4), exert their action through competetive occupation of the receptors. One compound, (S)-2-benzyloxycarbonyl-amino-3-[4-(10,11-dihydro-5H-dibenzo [a,d]cyclo-hepten-5-yloxy)piperidin-1-yl]propionic acid (4c), was tested in an in vitro guinea-pig asthma model. It exhibits much more potent inhibition (IC50 = 1.5 mu M) against antigen-induced contraction than either terfenadine or FPL55712, the reference drugs. As indicated by an ex vivo binding assay, the drug 4c does not readily pass the blood-brain barrier, and therefore is unlikely to cause sedating side-effects at a therapeutic dose.

  DOI：

  10.1016/s0223-5234(97)87535-6

文献信息

• Piperidine derivatives
  申请人：KOWA CO. LTD.

  公开号：EP0739881A2

  公开（公告）日：1996-10-30

  A piperidine derivative of formula (1) or salts thereof: wherein R1 and R2 independently represent H or together represent O, R3 represents H, -R5-COOR6, or -COOR6 (wherein R5 is a lower alkylene group, -CONH-, or -CONHCH2, and R6 is H or a lower alkyl group), R4 represents H, an aralkyloxy carbonyl group, an aminomethyl carbonyl group, or an aralkyloxy carbonyl aminomethyl carbonyl group, A represents O or a double bond, and the broken line has the meaning that a bonding hand may be present; and preventive and therapeutic agents for allergies, antihistaminic agents, and antileucotriene agents comprising the derivative or salts as their effective component. The compound of formula (1) has excellent antihistaminic activities and antileukotriene activities, which are well balanced, and is useful as a drug for the prevention and treatment of allergies such as asthma, allergic rhinitis, allergic dermatosis and urticaria.

  式（1）的哌啶衍生物或其盐： 其中 R1 和 R2 独立地代表 H 或一起代表 O，R3 代表 H、-R5-COOR6 或 -COOR6（其中 R5 是低级亚烷基、-CONH- 或 -CONHCH2，R6 是 H 或低级烷基），R4 代表 H、烷氧基羰基、氨甲基羰基或烷氧基羰基氨甲基羰基，A 代表 O 或双键，断线的含义是可能存在键手；以及预防和治疗过敏的制剂、抗组胺制剂和抗白三烯制剂，其中包含作为其有效成分的衍生物或盐。 式（1）的化合物具有优异的抗组胺活性和抗白三烯活性，二者平衡良好，可作为预防和治疗哮喘、过敏性鼻炎、过敏性皮肤病和荨麻疹等过敏症的药物。