3-[3-(哌啶-1-基甲基)苯氧基]丙酸 | 76955-75-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 中文名称: 3-[3-(哌啶-1-基甲基)苯氧基]丙酸
• 英文名称: GR 30450
• 英文别名: 3-[3-(piperidinomethyl)phenoxy]propionic acid；3-(3-Piperidinomethyl-phenoxy)-propionsaeure；Propanoic acid, 3-(3-(1-piperidinylmethyl)phenoxy)-；3-[3-(piperidin-1-ylmethyl)phenoxy]propanoic acid
• CAS: 76955-75-4
• 化学式: C₁₅H₂₁NO₃
• 分子量: 263.337
• InChiKey: GBECGCDVAVIEJP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.3
• 重原子数：
  19
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  49.8
• 氢给体数：
  1
• 氢受体数：
  4

安全信息

• 海关编码：
  2933399090

反应信息

• 作为反应物：
  描述：

  3-[3-(哌啶-1-基甲基)苯氧基]丙酸 在 氯化亚砜 作用下， 以 N-甲基乙酰胺 、 二氯甲烷 为溶剂， 生成 3-[3-(piperidinomethyl)phenoxy]propionyl chloride hydrochloride
  参考文献：
  名称：

  Histamine H.sub.2 -antagonist oxazole and thiazole derivatives and

  摘要：

  这项发明涉及氨基烷基苯氧基烷基取代的杂环化合物。这些化合物可以拮抗组胺在大脑组胺H.sub.2-受体上的作用。该发明的一种化合物是2-[3-[3-(哌啶甲基)苯氧基]丙基氨基]苯并噻唑。

  公开号：

  US04681883A1
• 作为产物：
  描述：

  3-<3-(1-Piperidinylmethyl)-phenoxy>-propionitrilhydrochlorid 在 盐酸 作用下， 反应 60.0h， 生成 3-[3-(哌啶-1-基甲基)苯氧基]丙酸
  参考文献：
  名称：

  H2 抗组胺药，第 36 届 Mitt. Isolamtidin 和类似物

  摘要：

  Isolamtidine (9a)，lamtidine (8a) 的位置异构体，以及类似的 N3 - 取代的 1 - 甲基 - 1H - 1,2,4 - 三唑 - 3,5 - 二胺 9e - i, k 是通过特定的方法制备的合成和对离体的豚鼠心房以及对组胺刺激的麻醉大鼠的酸分泌产生 H2 拮抗作用。

  DOI：

  10.1002/ardp.19873200708

文献信息

• Pyridine compounds
  申请人：Smith Kline & French Laboratories Limited

  公开号：US04952589A1

  公开（公告）日：1990-08-28

  This invention relates to aminoalkylphenoxyalkyl substituted heterocycles. These compounds antagonize the action of histamine on histamine H.sub.2 -receptors in the brain. A compound of the invention is 2-[3-[3-(piperidinomethyl)phenoxy]propylamino]benzthiazole.

  本发明涉及氨基烷基苯氧基烷基取代杂环化合物。这些化合物拮抗组胺在脑组织中的组胺H.sub.2 受体的作用。本发明的化合物是2-[3-[3-(哌啶甲基)苯氧基]丙基]苯并噻唑。
• 1,2,4-Triazole derivatives, processes for their production and pharmaceutical compositions containing them
  申请人：GLAXO GROUP LIMITED

  公开号：EP0016565A1

  公开（公告）日：1980-10-01

  The invention relates to compounds of the general formula (I) and physiologically acceptable salts, hydrates and bioprecursors thereof, in which R1 and R2, which may be the same of different, each represent hydrogen, C1-10 alkyl, cycloalkyl, alkenyl, alkynyl, aralkyl, trifluoroalkyl, or alkyl substituted by hydroxy, alkoxy, amino, alkylamino dialkylamino or cycloalkyl or R, and R2 may together with the nitrogen atom to which they are attached form a 5 to 10 membered ring which may be saturated or may contain at least one double bond, may be unsubstituted or may be substituted by one or more C1-3 alkyl groups or a hydroxy group and/or may contain another heteroatom which is oxygen or sulphur; Alk represents a straight or branched alkylene chain of 1 to 6 carbon atoms, Q represents a furan or thiophene ring in which incorporation into the rest of the molecule is through bonds at the 2-and 5- positions, the furan ring optionally bearing a further substituent R6 adjacent to the group R 1R2N-Alk, or Q represents a benzene ring in which incorporation into the rest of the molecule is through bonds at the 1 - and 3- or 1 - and 4. positions; R4 represents halogen or C1-4 alkyl which may be substi. tuted by hydroxy or C1-4 alkoxy; X represents -CH2-, -0-, -S- or where R5 represents hydrogen or methyl; n represents zero, 1 or 2; M represents 2, 3 or 4; R represents hydrogen, alkyl, alkenyl, aralkyl, hydroxyalkyl with at least two carbon atoms, alkoxyalkyl, or aryl, and R4 represents hydrogen, alkyl, alkenyl, aryl, aralkyl, hydroxyalkyl, acyloxyalkyl, alkoxyalkyl, aryloxyalkyl, aralkyloxyalkyl, aminoalkyl, alkylaminoalkyl, dialkylaminoalkyl, hydroxy, alkoxy, alkylthio or halogen or the group NR7R8 where R7 represents hydrogen, alkyl, alkenyl or aralkyl or R6 represents the group COR9 where R9 represents hydrogen, alkyl, aryl, aralkyl, alkoxy, heteroaryl or monocyclic heteroarylalkyl or R4 represents the group SO2R10 where R10 represents alkyl or aryl, or R8 represents the group where Y is oxygen or sulphur and R 11 represents hydrogen, alkyl, cycloalkyl, aryl or aralkyl. The compounds of formula (I) show pharmacological activity as selective histamine H2- antagonists.

  本发明涉及通式 (I) 的化合物 及其生理上可接受的盐、水合物和生物前体，其中 R1和R2（可以相同或不同）分别代表氢、C1-10烷基、环烷基、烯基、炔基、芳烷基、三氟烷基或被羟基、烷氧基、氨基、烷基氨基二烷基氨基或环烷基取代的烷基或 R、和 R2 可与它们所连接的氮原子一起形成一个 5 至 10 个成员的环，该环可以是饱和的，也可以含有至少一个双键，可以是未取代的，也可以是被一个或多个 C1-3 烷基或羟基取代的，和/或可以含有另一个氧或硫的杂原子； 烷基代表 1-6 个碳原子的直链或支链亚烷基、 Q 代表呋喃或噻吩环，通过 2-位和 5-位上的键与分子的其余部分结合，呋喃环可选择带有与基团 R 1R2N-Alk 相邻的另一个取代基 R6，或 Q 代表苯环，通过 1-位和 3-位或 1-位和 4-位上的键与分子的其余部分结合； R4 代表卤素或可被羟基或 C1-4 烷氧基取代的 C1-4 烷基； X 代表-CH2-、-0-、-S- 或-CH2-。 其中 R5 代表氢或甲基； n 代表零、1 或 2； M 代表 2、3 或 4； R 代表氢、烷基、烯基、芳基、至少含有两个碳原子的羟烷基、烷氧基烷基或芳基，以及 R4 代表氢、烷基、烯基、芳基、芳烷基、羟基烷基、酰氧基烷基、烷氧基烷基、芳氧基烷基、芳基氧基烷基、氨基烷基、烷基氨基烷基、二烷基氨基烷基、羟基、烷氧基、烷硫基或卤素或基团 NR7R8，其中 R7 代表氢、烷基、烯基或芳烷基或 R6 代表基团 COR9（其中 R9 代表氢、烷基、芳基、芳烷基、烷氧基、杂芳基或单环杂 芳烷基），或 R4 代表基团 SO2R10（其中 R10 代表烷基或芳基），或 R8 代表基团 NR7R8（其中 R7 代表氢、烷基、烯基或芳烷基）。 其中 Y 是氧或硫，R 11 代表氢、烷基、环烷基、芳基或芳烷基。 式（I）化合物具有选择性组胺 H2- 拮抗剂的药理活性。
• Heterocyclic phenoxy derivatives having an antihistamine H2 activity
  申请人：SMITH KLINE & FRENCH LABORATORIES LIMITED

  公开号：EP0181163A2

  公开（公告）日：1986-05-14

  Compounds of the formula (I): or pharmaceutically acceptable salts thereof, wherein : R1 and R2 are independently C1-4alkyl; or R1 and R2 together with the nitrogen atom to which they are joined represent a pyrrolidino, piperidino or hexahydroazepino ring; Y is straight-chain or branched-chain C1-4alkyl; n is 2 to 5; m is 0 or 1; when m is 1, Z is inter alia an optionally substituted pyridine, pyrimidine, oxazole, thiazole, imidazole, benzoxazole benzthiazole or N-alkylbenzimidazole ring; when m is 0, Z is an optionally substituted imidazole, pyrazole or benzimidazole ring. The compounds are histamine H2-receptors antagonists and relatively lipophilic and can penetrate the blood-brain barrier and are useful in treating diseases mediated via histamine H2-receptors. Processes for their preparation, pharmaceutical compositions and methods of use are described.

  式 (I) 的化合物： 或其药学上可接受的盐，其中： R1 和 R2 独立地为 C1-4 烷基；或 R1 和 R2 连同与之相连的氮原子代表吡咯烷、哌啶或六氢氮杂环； Y 为直链或支链 C1-4 烷基；n 为 2 至 5；m 为 0 或 1；当 m 为 1 时，Z 特别是任选取代的吡啶、嘧啶、噁唑、噻唑、咪唑、苯并噁唑苯并噻唑或 N-烷基苯并咪唑环；当 m 为 0 时，Z 是任选取代的咪唑、吡唑或苯并咪唑环。 这些化合物是组胺 H2 受体拮抗剂，具有相对亲脂性，可穿透血脑屏障，有助于治疗通过组胺 H2 受体介导的疾病。本文介绍了这些化合物的制备工艺、药物组合物和使用方法。
• Utility of hepatocytes to model species differences in the metabolism of loxtidine and to predict pharmacokinetic parameters in rat, dog and man
  作者：M. K. BAYLISS

  DOI：10.1080/004982599238650

  日期：1999.1

  1. The metabolism of loxtidine (1-methyl-5-[3-[3-[(1-piperidinyl) methyl] phenoxy] propyl] amino-1H-1,2,4-triazole-3-methanol) was studied in freshly isolated rat, dog and human hepatocytes. Metabolism in vitro was comparable with previously available in vivo data in all three species with the marked species differences observed in vivo being reproduced in the hepatocyte model.2. The major route for the metabolism of loxtidine by rat hepatocytes was N-dealkylation to form the propionic acid and hydroxymethyl triazole metabolites. A minor metabolic route was the oxidation of loxtidine to a carboxylic acid metabolite. The major route of metabolism for loxtidine in dog hepatocytes was glucuronidation with oxidation to the carboxylic acid metabolite being of minor importance. Incubation of loxtidine with human hepatocytes resulted in the drug remaining largely unchanged but with the carboxylic acid metabolite being produced in minor amounts.3. In vitro studies were undertaken with rat, dog and human hepatocytes to determine the Michaelis-Menten parameters V-max and K-m for the sum of all the metabolic pathways. These kinetic parameters were used to calculate the intrinsic clearance of loxtidine. Using appropriate scaling factors, the predicted in vivo hepatic clearance was then calculated. The predicted intrinsic clearances were 51.4+/-12.4, 8.0+/-0.8 and 1.0+/-0.6 ml/min/kg for rat, dog and human hepatocytes respectively. These data were then used to calculate hepatic clearances of 24.5, 3.1 and 0.2 ml/min/kg for rat, dog and man respectively.4. In vivo hepatic and intrinsic clearances for loxtidine were determined in rat, dog and human volunteers. The hepatic clearances of loxtidine were 26.6, 6.6 and 0.4 ml/min/kg in rat, dog and man respectively and intrinsic clearances were 58.5, 18.5 and 2.0 ml/min/kg in rat, dog and man respectively.5. The present studies demonstrate that the hepatocyte model map be a valuable in vitro tool for predicting both qualitative and quantitative aspects of the metabolism of a drug in animals and man at an early stage of the drug development process.
• US4536508A
  申请人：——

  公开号：US4536508A

  公开（公告）日：1985-08-20