1-{1-(4-氟苯基)甲基-1H-苯咪唑-2-基}-N-甲基-4-哌啶胺 | 108635-83-2

• 物质功能分类: 有机原料 - 杂环化合物
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并咪唑类
• 中文名称: 1-{1-(4-氟苯基)甲基-1H-苯咪唑-2-基}-N-甲基-4-哌啶胺
• 英文名称: 1-{1-[(4-Fluorophenyl)methyl]-1H-benzimidazol-2-yl}-N-methyl-4-piperidinamine
• 英文别名: 1-[1-[(4-fluorophenyl)methyl]-2(1H)-benzimidazolyl]-N-methyl-4-piperidinamine；1-[1-(4-fluorobenzyl)-1H-benzimidazol-2-yl]-N-methyl-4-aminopiperidine；1-(1-(4-fluorobenzyl)-1H-benzo[d]imidazol-2-yl)-N-methylpiperidin-4-amine；1-[1-[(4-fluorophenyl)methyl]benzimidazol-2-yl]-N-methylpiperidin-4-amine
• CAS: 108635-83-2
• 化学式: C₂₀H₂₃FN₄
• 分子量: 338.428
• InChiKey: LDMXQNXCFMLIER-UHFFFAOYSA-N

物化性质

• 沸点：
  519.6±60.0 °C(Predicted)
• 密度：
  1.23±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  25
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  33.1
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1-{1-(4-氟苯基)甲基-1H-苯咪唑-2-基}-N-甲基-4-哌啶胺 生成 3-cyano-1-[1-[1-[(4-fluorophenyl)methyl]benzimidazol-2-yl]piperidin-4-yl]-1,2-dimethylguanidine
  参考文献：
  名称：

  MANOURY, PHILIPPE;ROSSEY, GUY;BINET, JEAN;DEFOSSE, GERARD;JABRI, NAJIB

  摘要：

  DOI：
• 作为产物：
  描述：

  1-[1-(4-fluorobenzyl)-1H-benzimidazol-2-yl]-4-piperidone 在 甲胺 、 sodium tetrahydroborate 、 水 作用下， 以 甲醇 为溶剂， 反应 0.5h， 生成 1-{1-(4-氟苯基)甲基-1H-苯咪唑-2-基}-N-甲基-4-哌啶胺
  参考文献：
  名称：

  PROCESS AND INTERMEDIATES FOR OBTAINING 1-(1H-BENZIMIDAZOL-2-YL)-4-(PYRIMIDIN-2-YLAMINO)PIPERIDINE DERIVATIVES

  摘要：

  公开号：

  EP1564212B1

文献信息

• Benzimidazole derivatives and pharmaceutical compositions containing them
  申请人：Synthelabo

  公开号：US04820710A1

  公开（公告）日：1989-04-11

  Benzimidazole derivatives corresponding to the formula (1) ##STR1## in which X is CH or N, R.sub.1 is either a hydrogen atom, or a benzyl radical which can bear 1 to 3 substituents chosen from halogen atoms and trifluoromethyl, (C.sub.1-4)alkyl, (C.sub.1-4)alkoxy, cyano, methylthio, methylsulphinyl and methylsulphonyl radicals, or a methyl radical bearing a heterocyclic substituent in which the heterocyclic system can be a pyridyl, thienyl or furyl radical and can bear one or more substituents, R.sub.2 is a hydrogen atom or a (C.sub.1-4)alkyl radical, R.sub.3 is a hydrogen atom or a hydroxy radical, and R.sub.4 is a hydrogen atom or a (C.sub.1-4)alkyl radical, where appropriate, in tautomeric form when R.sub.3 is OH. The compounds may be used in treating allergy and histamine-induced inflammation.

  对应于公式（1）的苯并咪唑衍生物 ##STR1## 其中X为CH或N，R.sub.1为氢原子或苯甲基基团，可以承受1至3个取自卤素原子和三氟甲基，(C.sub.1-4)烷基，(C.sub.1-4)烷氧基，氰基，甲硫基，甲基磺酰氧基和甲基磺基基团的取代基，或者带有杂环取代基的甲基基团，在杂环系统中，杂环可以是吡啶基，噻吩基或呋喃基，可以承受一个或多个取代基，R.sub.2为氢原子或(C.sub.1-4)烷基基团，R.sub.3为氢原子或羟基基团，R.sub.4为氢原子或(C.sub.1-4)烷基基团，必要时，当R.sub.3为OH时，以互变异构体的形式存在。这些化合物可用于治疗过敏和组胺引起的炎症。
• Antihistaminic benzimidazole derivatives
  申请人：Synthelabo

  公开号：US04857536A1

  公开（公告）日：1989-08-15

  A compound which is a benzimidazole derivative of formula (I) ##STR1## in which: R.sub.1 is hydrogen or methyl, R.sub.2 is hydrogen, methyl or acetyl, R.sub.3 is hydrogen, methyl or acetyl, and R.sub.4 is hydrogen or a halogen, or a pharmaceutically acceptable acid addition salt thereof. The compounds have histamine antagonist activity and are also synthesis intermediates.

  一种化合物，为式(I)的苯并咪唑衍生物：##STR1## 其中：R.sub.1为氢或甲基，R.sub.2为氢、甲基或乙酰基，R.sub.3为氢、甲基或乙酰基，R.sub.4为氢或卤素，或其药学上可接受的酸盐。该化合物具有组胺拮抗活性，也是合成中间体。
• Process and intermediates for obtaining 1-(1H-benzimidazol-2-YL)-4-(2-aminopyrimidine)piperidine derivatives
  申请人：Lorente Bonde-Larsen Antonio

  公开号：US20050228006A1

  公开（公告）日：2005-10-13

  A method is provided for obtaining derivatives of 1-(1H-Benzimidazole-2-il)-4-(2-aminopyrimidine)piperidine (IV), wherein R 1 represents hydrogen or 4-halobenzul and R 5 represents optionally-substituted hydrogen, alkyl or benzyl. The method includes the conversion of a 1-[1-(R 1 )-1-(1H-Benzimidazole-2-il)-4-(R 2 )(R 3 )-piperidine (I), wherein R 2 or R 3 represents optionally-protected hydroxyl, or R 2 and R 3 represent, independently of each other, optionally-substituted alkoxy or benzyloxy, or R 2 and R 3 together form an optionally-substituted alkylenedioxy group, by hydrolysis and/or oxidation into a 1-[1-(R 1 )-1-(1H-Benzimidazole-2-il)-4-piperidone, which, by reductive amination (with optional separation of the intermediate imina formed) provides the corresponding amine which, by reaction with a pyrimidine, produces the above-mentioned derivative of 1-(1H-Benzimidazole-2-il)-4-(2-aminopyrimidine) piperidine (IV).

  提供了一种获得1-(1H-苯并咪唑-2-基)-4-(2-氨基嘧啶)哌啶衍生物(IV)的导数的方法，其中R1代表氢或4-卤苯甲酰，R5代表可选取代的氢、烷基或苄基。该方法包括将1-[1-(R1)-1-(1H-苯并咪唑-2-基)-4-(R2)(R3)-哌啶(I)，其中R2或R3代表可选的保护羟基，或R2和R3独立地代表可选取代的烷氧基或苄氧基，或R2和R3一起形成可选取代的烷二酰基基团，通过水解和/或氧化转化为1-[1-(R1)-1-(1H-苯并咪唑-2-基)-4-哌啶酮，通过还原胺化（可选分离中间产物亚胺）提供相应的胺，该胺通过与嘧啶反应产生上述的1-(1H-苯并咪唑-2-基)-4-(2-氨基嘧啶)哌啶衍生物（IV）。
• METHOD AND INTERMEDIA USED TO OBTAIN DERIVATIVES OF 1-(1H- BENZIMIDAZOLE-2-YL)-4-(2-AMINOPYRIMIDINE)PIPERIDINE
  申请人：Ragactives, S.L.

  公开号：EP1564212A1

  公开（公告）日：2005-08-17

  The invention relates to a method of obtaining derivatives of 1-(1H-benzimidazole-2-il)-4-(2-aminopyrimidine)piperidine (IV), wherein - R1 represents hydrogen or 4-halobenzyl and R5 represents optionally-substituted hydrogen, alkyl or benzyl. The inventive method comprises the conversion of a 1-[1-(R1)-1H-benzimidazole-2-il]-4-(R2)(R3)-piperidine (I), wherein R2 or R3 represents optionally-protected hydroxy, or R2 and R3 represent, independently of each other, optionally-substituted alkoxy or benzyloxy, or R2 and R3 together form an optionally-substituted alkylenedioxy group, by means of hydrolysis and/or oxidation into a 1-[1-(R1)-1H-benzimidazole-2-il]-4-piperidone, which, by reductive amination (with optional separation of the intermediate imina formed) provides the corresponding amine which, by reaction with a pyrimidine, produces the above-mentioned derivative of 1-(1H-benzimidazole-2-il)-4-(2-aminopyrimidine) piperidine (IV).

  本发明涉及一种获得1-(1H-苯并咪唑-2-il)-4-(2-氨基嘧啶)哌啶(IV)衍生物的方法，其中-R1代表氢或4-卤代苄基，R5代表任选取代的氢、烷基或苄基。本发明的方法包括将 1-[1-(R1)-1H-苯并咪唑-2-il]-4-(R2)(R3)-哌啶（I）转化，其中 R2 或 R3 代表任选保护的羟基，或 R2 和 R3 各自代表任选取代的烷氧基或苄氧基，或 R2 和 R3 共同形成任选取代的烷二氧基、通过水解和/或氧化，生成 1-[1-(R1)-1H-苯并咪唑-2-il]-4-哌啶酮，通过还原胺化（可选择分离形成的中间亚胺），提供相应的胺，通过与嘧啶反应，生成上述 1-(1H-苯并咪唑-2-il)-4-(2-氨基嘧啶)哌啶衍生物(IV)。
• Brain-penetrating 2-aminobenzimidazole H1-antihistamines for the treatment of insomnia
  作者：Timothy Coon、Wilna J. Moree、Binfeng Li、Jinghua Yu、Said Zamani-Kord、Siobhan Malany、Mark A. Santos、Lisa M. Hernandez、Robert E. Petroski、Aixia Sun、Jenny Wen、Sue Sullivan、Jason Haelewyn、Michael Hedrick、Samuel J. Hoare、Margaret J. Bradbury、Paul D. Crowe、Graham Beaton

  DOI：10.1016/j.bmcl.2009.05.086

  日期：2009.8

  The benzimidazole core of the selective non-brain-penetrating H-1-antihistamine mizolastine was used to identify a series of brain-penetrating H-1-antihistamines for the potential treatment of insomnia. Using cassette PK studies, brain-penetrating H-1-antihistamines were identified and in vivo efficacy was demonstrated in a rat EEG/EMG model. Further optimization focused on strategies to attenuate an identified hERG liability, leading to the discovery of 4i with a promising in vitro pro. le. (C) 2009 Elsevier Ltd. All rights reserved.