N-[2-[4-(Hydroxymethyl)-1-piperidinyl]ethyl]methanesulphonamide | 144625-74-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: N-[2-[4-(Hydroxymethyl)-1-piperidinyl]ethyl]methanesulphonamide
• 英文别名: N-(2-(4-(Hydroxymethyl)piperidin-1-yl)ethyl)methanesulfonamide；N-[2-[4-(hydroxymethyl)piperidin-1-yl]ethyl]methanesulfonamide
• CAS: 144625-74-1
• 化学式: C₉H₂₀N₂O₃S
• 分子量: 236.335
• InChiKey: NTISJUGLKHBAHV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.6
• 重原子数：
  15
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  78
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  5-氟吲哚-3-甲酸 、 N-[2-[4-(Hydroxymethyl)-1-piperidinyl]ethyl]methanesulphonamide 在 甲烷磺酸 、 三氟乙酸酐 作用下， 以 二氯甲烷 为溶剂， 反应 16.0h， 以29%的产率得到[1-[2-[(Methylsulphonyl)amino]ethyl]-4-piperidinyl]methyl 5-fluoro-1H-indole-3-carboxylate
  参考文献：
  名称：

  Synthesis of GR 125487, a selective 5-HT₄ receptor antagonist

  摘要：

  The 5-HT4 receptor (5-HT4R) agonists are important in treating gastrointestinal motility disorders. Their role is currently being evaluated for the treatment of cognitive and mood disorders. A selective 5-HT4R antagonist GR 125487 is used in many biological assays to cross confirm the 5-HT4R agonist's activity. A practical synthesis of GR 125487 is developed so as to have it in desired quantities. The synthesis consists of seven steps starting from commercially available methyl 5-fluoroindole 3-carboxylate. The GR 125487 thus synthesized was used in blocking the activity of 5-HT4R agonist compound in animal models of cognition.

  DOI：

  10.1080/00397911.2016.1178297
• 作为产物：
  描述：

  4-哌啶甲醇 、 N,N-二异丙基乙胺 、 N-(2-溴乙基)甲烷磺酰胺 以 乙腈 为溶剂， 反应 2.0h， 以to give the title compound (1.80 g) as a solid, m.p. 81°-82°的产率得到N-[2-[4-(Hydroxymethyl)-1-piperidinyl]ethyl]methanesulphonamide
  参考文献：
  名称：

  Substituted phenylcarbamates and phenylureas, their preparation and

  摘要：

  公式（I）中的取代苯基氨基甲酸酯和脲化物 其中R1代表氢或卤素原子，或C1-6烷基，C1-6烷氧基或羟基；R2代表噁二唑或噻二唑环，被来自C1-6烷基，C3-7环烷基，-CH2C2-5烯基，-CH2C2-5炔基，苯基或苄基的基团取代；X代表NH或氧原子；m代表零，1或2；R3代表C1-6烷基，苄基，-(CH2)nR4或 其中R4代表从氰基，羟基，C1-6烷氧基，苯氧基，C（O）C1-6烷基，C（O）C6H5，-CONR6R7，-NR6COR7，-SO2NR6R7或-NR6SO2R7中选择的基团（其中R6和R7中的每一个都独立地代表氢原子，C1-6烷基或苯基）；n代表2或3；R5代表COR8或SO2R8 其中R8代表氢原子，C1-6烷基或苯基）；以及季铵衍生物，哌啶N-氧化物和制药上可接受的盐和溶剂，这些化合物是5-羟色胺（5HT；血清素）的有效和特异性拮抗剂。

  公开号：

  US05618827A1

文献信息

• 2-Oxadiazolyl- or 2-thiadiazolyl-phenylcarbamate and -phenylurea derivatives, their preparation and their use as intermediates
  申请人：GLAXO GROUP LIMITED

  公开号：EP0972773A1

  公开（公告）日：2000-01-19

  The present invention relates to substituted carbamates and ureas of formula (V) wherein R1 represents a hydrogen or a halogen atom, or a C1-6alkyl, C1-6alkoxy or hydroxy group; R2 represents an oxadiazole or thiadiazole ring substituted by a group selected from C1-6alkyl, C3-7cycloalkyl, -CH2C2-5alkenyl, -CH2C2-5alkynyl, phenyl or benzyl; X represents NH or an oxygen atom; and m represents zero, 1 or 2; which compounds are intermediates in the preparation of certain therapeutically active substituted phenylcarbamates and ureas.

  本发明涉及式（V）的取代氨基甲酸酯和脲，其中 R1 代表氢或卤原子，或 C1-6烷基、C1-6烷氧基或羟基；R2 代表被选自 C1-6烷基、C3-7环烷基、-CH2C2-5烯基、-CH2C2-5炔基、苯基或苄基的基团取代的噁二唑或噻二唑环； X代表NH或氧原子；m代表0、1或2；这些化合物是制备某些具有治疗活性的取代苯基氨基甲酸酯和脲的中间体。
• Benzimidazole derivatives. Part 1: Synthesis and structure–activity relationships of new benzimidazole-4-carboxamides and carboxylates as potent and selective 5-HT4 receptor antagonists
  作者：Marı́a L. López-Rodrı́guez、Bellinda Benhamú、Alma Viso、M.José Morcillo、Marta Murcia、Luis Orensanz、M.José Alfaro、M.Isabel Martı́n

  DOI：10.1016/s0968-0896(99)00172-8

  日期：1999.11

  New benzimidazole-4-carboxamides 1-16 and -carboxylates 17-26 were synthesized and evaluated for binding affinity at serotonergic 5-HT4 and 5-HT3 receptors in the CNS. Most of the synthesized compounds exhibited moderate to-very high affinity tin many cases subnanomolar) for the 5-HT4 binding site and no significant affinity for the 5-HT3 receptor. SAR observations and structural analyses (molecular modeling, INSIGHT II) indicated that the presence of a voluminous substituent in the basic nitrogen atom of the amino moiety and a distance of ca. 8.0 Angstrom from this nitrogen to the aromatic ring are of great importance for high affinity and selectivity for 5-HT4 receptors. These results confirm our recently proposed model for recognition by the 5-HT4 binding site. Amides 12-15 and esters 24 and 25 bound at central 5-HT4 sites with very high affinity (K-j = 0.11-2.9 nM) and excellent selectivity over serotonin 5-HT3, 5-HT2A, and S-HT1A receptors (K-i > 1000-10,000 nM). Analogues 12 (k(i)(5-HT4) = 0.32 nM), 13 (K-i(5-HT4)= 0.11 nM), 14 (K-i(5-HT4) = 0.29 nM) and 15 (K-i(5-HT4) = 0.54 nM) were pharmacologically characterized as selective 5-HT4 antagonists in the isolated guinea pig ileum (pA(2) = 7.6, 7.9, 8.2 and 7.9, respectively), with a potency comparable to the 5-HT4 receptor antagonist RS 39604 (pA(2) = 8.2). The benzimidazoe-4-carboxylic acid derivatives described in this paper represent a novel class of potent and selective 5-HT4 receptor antagonists. In particular, compounds 12-15 could be interesting pharmacological tools for the understanding of the role of 5-HT4 receptors. (C) 1999 Elsevier Science Ltd. All rights reserved.
• 3-Piperidinylmethylcarboxylate substituted indoles
  申请人：GLAXO GROUP LIMITED

  公开号：EP0501322B1

  公开（公告）日：1996-09-04
• SUBSTITUTED PHENYLCARBAMATES AND PHENYLUREAS, THEIR PREPARATION AND THEIR USE AS 5-HT ANTAGONISTS
  申请人：GLAXO GROUP LIMITED

  公开号：EP0640081A1

  公开（公告）日：1995-03-01
• SUBSTITUTED PHENYLCARBAMATES AND PHENYLUREAS, THEIR PREPARATION AND THEIR USE AS 5-HT4 ANTAGONISTS
  申请人：GLAXO GROUP LIMITED

  公开号：EP0640081B1

  公开（公告）日：2000-01-12