[1-(2-methanesulfonylaminoethyl)-4-piperidyl]methylamine | 152820-99-0

• 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: [1-(2-methanesulfonylaminoethyl)-4-piperidyl]methylamine
• 英文别名: N-{2-[4-(aminomethyl)piperidin-1-yl]ethyl}methanesulfonamide；N-[2-[4-(aminomethyl)piperidin-1-yl]ethyl]methanesulfonamide
• CAS: 152820-99-0
• 化学式: C₉H₂₁N₃O₂S
• 分子量: 235.351
• InChiKey: WOWBWHAEKZIKSE-UHFFFAOYSA-N

物化性质

• 沸点：
  376.0±48.0 °C(Predicted)
• 密度：
  1.141±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.8
• 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：
  83.8
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  4-氨基-5-氯-2-甲氧基苯甲酸 、 [1-(2-methanesulfonylaminoethyl)-4-piperidyl]methylamine 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 4-amino-5-chloro-N-[1-[2-[(methylsulfonyl)amino]ethyl]-4-piperidinylmethyl]-2-methoxybenzamide
  参考文献：
  名称：

  Synthesis and pharmacological evaluation of carboxamide derivatives as selective serotoninergic 5-HT4 receptor agonists

  摘要：

  A number of new carboxamide derivatives were synthesized. The affinity of these compounds for the serotoninergic 5-HT4 receptor was evaluated by use of radioligand-binding techniques. The agonistic activity was evaluated as the contractile effect of the ascending colon isolated from guinea-pigs. Among these compounds, 4-amino-5-chloro-2-methoxy-N-[1-[2-[(methylsulfonyl)amino]ethyl]-4-piperidinylmethyl]benzamide (24) showed a high affinity for the 5-HT4 receptor (Ki = 9.6 nM). Compound 24 displayed a higher affinity for 5-HT4 receptors than the other receptors, including, 5-HT3 and dopamine D-2 receptors. In addition, compound 24 was confirmed to be a potent 5-HT4 receptor agonist (ED50 = 7.0 nM). An interaction model between compound 24 and 5-HT4 receptor was proposed. (C) 1999 Editions scientifiques et medicales Elsevier SAS.

  DOI：

  10.1016/s0223-5234(99)00158-0
• 作为产物：
  描述：

  N-(2-氯乙基)甲烷磺酰胺 、 4-氨甲基哌啶 以 乙腈 为溶剂， 以49%的产率得到[1-(2-methanesulfonylaminoethyl)-4-piperidyl]methylamine
  参考文献：
  名称：

  Benzimidazole derivatives. Part 1: Synthesis and structure–activity relationships of new benzimidazole-4-carboxamides and carboxylates as potent and selective 5-HT4 receptor antagonists

  摘要：

  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.

  DOI：

  10.1016/s0968-0896(99)00172-8

文献信息

• [EN] N-SUBSTITUTED PIPERIDINYL-IMIDAZOPYRIDINE COMPOUNDS AS 5-HT4 RECEPTOR MODULATORS<br/>[FR] COMPOSES DE PIPERIDINYL-IMIDAZOPYRIDINE N-SUBSTITUES UTILISES COMME MODULATEURS DU RECEPTEUR 5-HT4
  申请人：PFIZER PHARMA

  公开号：WO2004026868A1

  公开（公告）日：2004-04-01

  This invention provides a compound of the formula (I): wherein Rl represents a hydrogen atom or a halogen atom; R2 represents a hydrogen atom, etc.; R3 represents an alkyl group having from 1 to 10 carbon atoms; said alkyl group in R3 is substituted by at least one substituent selected from the group consisting of substituents α ; said substituents α are selected from the group consisting of aryl groups, hydroxy groups, oxo groups, etc.; said aryl groups have 6 to 10 carbon atoms; said aryl groups are unsubstituted or substituted by at least one alkyl group having from 1 to 6 carbon atoms; said heterocyclic groups and heterocyclic moiety in heterocycliccarbonyl groups are 5- to 10-membered cyclic groups containing from 1 to 4 heteroatoms selected from the group consisting of nitrogen atoms, etc.; or a pharmaceutically acceptable amide of such compound, or a pharmaceutically acceptable ester of such compound, and pharmaceutically acceptable salts thereof. These compounds have 5-HT4 receptor binding activity, and thus are useful for the treatment of gastroesophageal reflux disease, non-ulcer dyspepsia, functional dyspepsia, irritable bowel syndrome or the like in mammalian, especially humans. This invention also provides a pharmaceutical composition comprising the above compound.

  这项发明提供了一个化合物的结构式(I)：其中R1代表氢原子或卤原子；R2代表氢原子，等等；R3代表具有1至10个碳原子的烷基基团；R3中的烷基基团被来自α取代基组的至少一个取代基所取代；所述α取代基选自芳基、羟基、酮基等组成的组；所述芳基含有6至10个碳原子；所述芳基未取代或被具有1至6个碳原子的至少一个烷基基团所取代；所述杂环基团和杂环基团中的杂环基在杂环羰基中是含有1至4个来自氮原子等组成的杂原子的5至10元环基团；或者是该化合物的药学上可接受的酰胺，或者是该化合物的药学上可接受的酯，以及其药学上可接受的盐。这些化合物具有5-HT4受体结合活性，因此对于哺乳动物，特别是人类的胃食管反流病、非溃疡性消化不良、功能性消化不良、肠易激综合征等的治疗是有用的。该发明还提供了包含上述化合物的药物组合物。
• Substituted phenylcarbamates and phenylureas, their preparation and
  申请人：Glaxo Group Limited

  公开号：US05618827A1

  公开（公告）日：1997-04-08

  Substituted phenylcarbamates and ureas of formula (I) ##STR1## wherein R.sup.1 represents a hydrogen or a halogen atom, or a C.sub.1-6 alkyl, C.sub.1-6 alkoxy or hydroxy group; R.sup.2 represents an oxadiazole or thiadiazole ring substituted by a group selected from C.sub.1-6 alkyl, C.sub.3-7 cycloalkyl, --CH.sub.2 C.sub.2-5 alkenyl, --CH.sub.2 C.sub.2-5 alkynyl, phenyl or benzyl; X represents NH or an oxygen atom; m represents zero, 1 or 2; R.sup.3 represents C.sub.1-6 alkyl, benzyl, --(CH.sub.2).sub.n R.sup.4 or ##STR2## R.sup.4 represents a group selected from cyano, hydroxyl, C.sub.1-6 alkoxy, phenoxy, C(O)C.sub.1-6 alkyl, C(O)C.sub.6 H.sub.5, --CONR.sup.6 R.sup.7, --NR.sup.6 COR.sup.7, --SO.sub.2 NR.sup.6 R.sup.7 or --NR.sup.6 SO.sub.2 R.sup.7 (wherein each of R.sup.6 and R.sup.7 independently represent a hydrogen atom, a C.sub.1-6 alkyl or phenyl group); n represents 2 or 3; R.sup.5 represents COR.sup.8 or SO.sub.2 R.sup.8 (wherein R.sup.8 represents a hydrogen atom, a C.sub.1-6 alkyl or phenyl group); and quaternary ammonium derivatives, piperidine N-oxides and pharmaceutically acceptable salts and solvates thereof; which compounds are potent and specific antagonists of 5-hydroxytryptamine (5HT; serotonin).

  公式（I）的取代苯基氨基甲酸酯和脲类化合物 其中，R1代表氢原子、卤素原子或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、苯基或苄基的基取代的噁二唑或噻二唑环；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或的基式； R4代表被选自氰基、羟基、C1-6烷氧基、苯氧基、C（O）C1-6烷基、C（O）C6H5、-CONR6R7、-NR6COR7、-SO2NR6R7或-NR6SO2R7（其中R6和R7各自独立地代表氢原子、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-氧化物和药学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。
• N-substituted piperidinyl-imidazopyridine compounds as 5-HT4 receptor modulators
  申请人：Pfizer Inc

  公开号：US20040127514A1

  公开（公告）日：2004-07-01

  This invention provides a compound of the formula (I): 1 or a pharmaceutically acceptable salt, amide or ester thereof, wherein R 1 represents a hydrogen atom or a halogen atom; R 2 represents a hydrogen atom, etc.; R 3 represents an alkyl group having from 1 to 10 carbon atoms; said alkyl group of R 3 is substituted by at least one substituent selected from the group consisting of substituents &agr;; said substituents &agr; is aryl, hydroxy, oxo, etc.; said aryl having 6 to 10 carbon atoms; said aryl is unsubstituted or substituted by at least one alkyl group having from 1 to 6 carbon atoms; said heterocyclic and the heterocyclic moiety of said heterocycliccarbonyl, both of substituents &agr;, are 5- to 10-membered cyclic groups containing from 1 to 4 heteroatoms selected from the group consisting of nitrogen atoms, oxygen atoms and sulfur atoms These compounds have 5-HT 4 receptor binding activity, and thus are useful for the treatment of gastroesophageal reflux disease, non-ulcer dyspepsia, functional dyspepsia, irritable bowel syndrome or the like in mammalian, especially humans. This invention also provides a pharmaceutical composition comprising the above compound.

  本发明提供了化合物(I)的化合物：1或其药学上可接受的盐，酰胺或酯，其中R1代表氢原子或卤素原子; R2代表氢原子等; R3代表具有1到10个碳原子的烷基基团; R3的烷基基团被选自取代基&agr;的至少一种取代; 该取代基&agr;是芳基，羟基，氧代或其他; 该芳基具有6到10个碳原子; 该芳基未取代或被至少一个具有1到6个碳原子的烷基基团取代; 该杂环和该杂环羰基的杂环基团，取代基&agr;均为5至10个成员的环状基团，包含1至4个选自氮原子，氧原子和硫原子的杂原子。这些化合物具有5-HT4受体结合活性，因此对于哺乳动物，特别是人类的胃食管反流病，非溃疡性消化不良，功能性消化不良，肠易激综合征或类似疾病的治疗有用。本发明还提供了包含上述化合物的制药组合物。
• N-PIPERIDINYL ACETAMIDE DERIVATIVES AS CALCIUM CHANNEL BLOCKERS
  申请人：PAJOUHESH Hassan A.

  公开号：US20130065926A1

  公开（公告）日：2013-03-14

  Methods and compounds effective in ameliorating conditions characterized by unwanted calcium channel activity, particularly unwanted T-type calcium channel activity are disclosed. Specifically, a series of compounds containing N-piperidinyl acetamide derivatives as shown in formula (1).

  本发明揭示了在改善其特征为不需要的钙通道活性，特别是不需要的T型钙通道活性的情况下有效的方法和化合物。具体来说，本发明揭示了一系列包含N-哌啶基乙酰胺衍生物的化合物，如公式（1）所示。
• 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。