4-(9H-thioxanthen-9-ylidene)-1-piperidinepropionic acid

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并噻喃类
• 英文名称: 4-(9H-thioxanthen-9-ylidene)-1-piperidinepropionic acid
• 英文别名: 3-(4-Thioxanthen-9-ylidenepiperidin-1-yl)propanoic acid
• 化学式: C₂₁H₂₁NO₂S
• 分子量: 351.469
• InChiKey: BHWOMELFYOUNFI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  25
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  65.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  3-(4-Thioxanthen-9-ylidene-piperidin-1-yl)-propionic acid ethyl ester; hydrochloride 在 sodium hydroxide 作用下， 以 甲醇 为溶剂， 反应 1.5h， 以88%的产率得到4-(9H-thioxanthen-9-ylidene)-1-piperidinepropionic acid
  参考文献：
  名称：

  Amphoteric Drugs. II. Synthesis and Antiallergic Activity of (4-(5H-Dibenzo(a,d)cyclohepten-5-ylidene)piperidino)alkanoic Acid Derivatives and Related Compounds.

  摘要：

  描述了一种将经典三环抗组胺药物转化为具有相同效力的无镇静抗过敏剂的简单方法，适用于大鼠和豚鼠。合成了一系列[4-(5H-二苯并[a, d]环庚烯-5-亚基)-哌啶基]烷酸衍生物（6a）及相关化合物（6b-f），并与相应的N-甲基衍生物（2a-f）比较了其抗过敏和抗组胺活性以及对中枢神经系统（CNS）的影响。N-烷基羧酸（6a-f）在大鼠48小时同源被动皮肤过敏反应（PCA）中的抑制作用强于2a-f，并且在小鼠六氟巴比妥诱导麻醉的睡眠时间延长方面效果不如2a-f。进一步修饰的结果发现，在两性化合物的三环系统中心环中引入氧原子增强了它们的抗过敏和抗组胺活性。3-[4-(6H-二苯并[b, e]氧烯-11-亚基)哌啶基]丙酸（6c）在大鼠48小时同源PCA中表现出强的抑制作用（ED50=0.067mg/kg，口服），以及在麻醉豚鼠中对组胺诱导的支气管收缩的抑制作用（ED50=0.0085mg/kg，口服），因此是一个有前景的抗过敏剂候选物。

  DOI：

  10.1248/cpb.42.2285

文献信息

• Piperidine compounds, method for preparation thereof, and a pharamceutical composition comprising the same
  申请人：HOKURIKU PHARMACEUTICAL CO., LTD.

  公开号：EP0451772A1

  公开（公告）日：1991-10-16

  Novel piperidine compounds represented by the following formula (I): wherein Y represents an alkylene group having 1 to 7 carbon atoms; A is a group represented by formula I-a or formula I-b: wherein X represents -CH₂-S- or -S-; and R represents a hydrogen atom or a lower alkyl group with a proviso that A is a group represented by formula I-a, or R represents a hydrogen atom with a proviso that A is a group represented by formula I-b and pharmacologically acceptable salts thereof are disclosed. Also disclosed are a method for preparing the same; a pharmaceutical composition comprising the same; an antiallergic agent and an agent for bronchial asthma comprising the same; and a method for treatment of an allergic disease or bronchial asthma comprising the step of administering the same.

  本发明公开了以下式子（I）所表示的新型哌啶化合物：其中，Y代表具有1至7个碳原子的烷基；A是由式子I-a或式子I-b表示的基团：其中，X代表-CH₂-S-或-S-；R代表氢原子或较低的烷基，但在A是由式子I-a表示的基团时，R代表氢原子；在A是由式子I-b表示的基团时，R代表氢原子，其药理学上可接受的盐也被揭示。本发明还公开了一种制备该化合物的方法；包含该化合物的制药组合物；包含该化合物的抗过敏剂和支气管哮喘剂；以及通过给予该化合物进行治疗过敏性疾病或支气管哮喘的方法。
• Amphoteric Drugs. II. Synthesis and Antiallergic Activity of (4-(5H-Dibenzo(a,d)cyclohepten-5-ylidene)piperidino)alkanoic Acid Derivatives and Related Compounds.
  作者：Nobuhiko IWASAKI、Jun SAKAGUCHI、Tetsuo OHASHI、Masahiro YAMAZAKI、Nobuo OGAWA、Shingo YASUDA、Eiichi KOSHINAKA、Hideo KATO、Yasuo ITO、Hiroyuki SAWANISHI

  DOI：10.1248/cpb.42.2285

  日期：——

  A simple method of transforming clalssical tricyclic antihistaminics into nonsedative antiallergic agents with equal potency in rats and guinea-pigs is described. A series of [4-(5H-dibenzo[a, d]cyclohepten-5-ylidene)-piperidino]alkanoic acid derivatives (6a) and related compounds (6b-f) were synthesized and examined for antiallergic and antihistaminic activities and effects on the central nervous system (CNS) in comparison with the corresponding N-methyl derivatives (2a-f). N-Alkylcarboxylic acids (6a-f) showed stronger inhibitory effects on 48h homologous passive cutaneous anaphylaxis (PCA) in rats than 2a-f, and also were less effective in prolongation of the sleeping time on hexobarbital-induced anesthesia in mice in comparison with 2a-f. As a result of further modification, it was found that introduction of an oxygen atom into the central ring of the tricyclic system in amphoteric compounds enhanced their antiallergic and antihistaminic activities. 3-[4-(6H-Dibenz[b, e]oxepin-11-ylidene)piperidino]propionic acid (6c) exhibited strong inhibitory effects on 48h homologous PCA in rats (ED50=0.067mg/kg, p.o.) and on histamine-induced bronchoconstriction in anesthetized guinea-pigs (ED50=0.0085mg/kg, p.o.), and thus is a promising candidate as an antiallergic agent.

  描述了一种将经典三环抗组胺药物转化为具有相同效力的无镇静抗过敏剂的简单方法，适用于大鼠和豚鼠。合成了一系列[4-(5H-二苯并[a, d]环庚烯-5-亚基)-哌啶基]烷酸衍生物（6a）及相关化合物（6b-f），并与相应的N-甲基衍生物（2a-f）比较了其抗过敏和抗组胺活性以及对中枢神经系统（CNS）的影响。N-烷基羧酸（6a-f）在大鼠48小时同源被动皮肤过敏反应（PCA）中的抑制作用强于2a-f，并且在小鼠六氟巴比妥诱导麻醉的睡眠时间延长方面效果不如2a-f。进一步修饰的结果发现，在两性化合物的三环系统中心环中引入氧原子增强了它们的抗过敏和抗组胺活性。3-[4-(6H-二苯并[b, e]氧烯-11-亚基)哌啶基]丙酸（6c）在大鼠48小时同源PCA中表现出强的抑制作用（ED50=0.067mg/kg，口服），以及在麻醉豚鼠中对组胺诱导的支气管收缩的抑制作用（ED50=0.0085mg/kg，口服），因此是一个有前景的抗过敏剂候选物。