1-(thiophen-2-ylsulfonyl)piperidine-3-carboxylic acid | 329909-94-6

• 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-(thiophen-2-ylsulfonyl)piperidine-3-carboxylic acid
• 英文别名: 1-(Thiophene-2-sulfonyl)-piperidine-3-carboxylic acid；1-thiophen-2-ylsulfonylpiperidine-3-carboxylic acid
• CAS: 329909-94-6
• 化学式: C₁₀H₁₃NO₄S₂
• mdl: MFCD01925605
• 分子量: 275.35
• InChiKey: RITOUJDZVRPURH-UHFFFAOYSA-N

物化性质

• 沸点：
  485.7±55.0 °C(Predicted)
• 密度：
  1.476±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  17
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  111
• 氢给体数：
  1
• 氢受体数：
  6

安全信息

• 危险等级：
  IRRITANT

反应信息

• 作为反应物：
  描述：

  2-(4-氨基苯基)-6-甲基苯并噻唑 、 1-(thiophen-2-ylsulfonyl)piperidine-3-carboxylic acid 在 4-二甲氨基吡啶 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 二氯甲烷 为溶剂， 以29%的产率得到N-(4-(6-methylbenzo[d]thiazol-2-yl)phenyl)-1-(thiophen-2-ylsulfonyl)piperidine-3-carboxamide
  参考文献：
  名称：

  Synthesis and Evaluation of Benzothiazole-Based Analogues as Novel, Potent, and Selective Fatty Acid Amide Hydrolase Inhibitors

  摘要：

  High-throughput screening (HTS) identified benzothiazole analogue 3 as a potent fatty acid amide hydrolase (FAAH) inhibitor. Structure-activity relationship (SAR) studies indicated that the sulfonyl group, the piperidine ring and benzothiazole were the key components to their activity, with 16j being the most potent analogue in this series. Time-dependent preincubation study of compound 3 was consistent with it being a reversible inhibitor. Activity-based protein-profiling (ABPP) evaluation of 3 in rat tissues revealed that it had exceptional selectivity and no off-target activity with respect to other serine hydrolases. Molecular shape overlay of 3 with a known FAAH inhibitor indicated that these compounds might act as transition-state analogues, forming putative hydrogen bonds with catalytic residues and mimicking the charge distribution of the tetrahedral transition state. The modeling study also indicated that hydrophobic interactions of the benzothiazole ring with the enzyme contributed to its extraordinary potency. These compounds may provide useful tools for the study of FAAH and the endocannabinoid system.

  DOI：

  10.1021/jm801042a
• 作为产物：
  描述：

  2-噻吩磺酰氯 、 3-哌啶甲酸 在 碳酸氢钠 作用下， 以 水 、 丙酮 为溶剂， 反应 1.0h， 以50%的产率得到1-(thiophen-2-ylsulfonyl)piperidine-3-carboxylic acid
  参考文献：
  名称：

  Synthesis and Evaluation of Benzothiazole-Based Analogues as Novel, Potent, and Selective Fatty Acid Amide Hydrolase Inhibitors

  摘要：

  High-throughput screening (HTS) identified benzothiazole analogue 3 as a potent fatty acid amide hydrolase (FAAH) inhibitor. Structure-activity relationship (SAR) studies indicated that the sulfonyl group, the piperidine ring and benzothiazole were the key components to their activity, with 16j being the most potent analogue in this series. Time-dependent preincubation study of compound 3 was consistent with it being a reversible inhibitor. Activity-based protein-profiling (ABPP) evaluation of 3 in rat tissues revealed that it had exceptional selectivity and no off-target activity with respect to other serine hydrolases. Molecular shape overlay of 3 with a known FAAH inhibitor indicated that these compounds might act as transition-state analogues, forming putative hydrogen bonds with catalytic residues and mimicking the charge distribution of the tetrahedral transition state. The modeling study also indicated that hydrophobic interactions of the benzothiazole ring with the enzyme contributed to its extraordinary potency. These compounds may provide useful tools for the study of FAAH and the endocannabinoid system.

  DOI：

  10.1021/jm801042a

文献信息

• Aryl sulfonyl piperidines
  申请人：Gillespie Paul

  公开号：US20060199816A1

  公开（公告）日：2006-09-07

  Provided herein are compounds of the formula (1): as well as pharmaceutically acceptable salts thereof, wherein the substituents are as those disclosed in the specification. These compounds, and the pharmaceutical compositions containing them, are useful for the treatment of diseases such as, for example, type II diabetes mellitus and metabolic syndrome.

  本文提供了以下式（1）的化合物： 以及其药学上可接受的盐，其中取代基如规范中所披露的那样。这些化合物及含有它们的药物组合物对于治疗诸如II型糖尿病和代谢综合征等疾病是有用的。
• 1-SULFONYL-PIPERDINE-3-CARBOXYLIC ACID AMIDE DERIVATIVES AS INHIBITORS OF 11-BETA-HYDROXYSTEROID DEHYDROGENASE FOR THE TREATMENT OF TYPE II DIABETES MELLITUS
  申请人：F. Hoffmann-La Roche AG

  公开号：EP1866285A1

  公开（公告）日：2007-12-19
• [EN] 1- SULFONYL-PI PERDINE- 3 -CARBOXYL I C ACID AMIDE DERIVATIVES AS INHIBITORS OF 11-BETA-HYDROXYSTEROID DEHYDROGENASE FOR THE TREATMENT OF TYPE II DIABETES MELLITUS<br/>[FR] DERIVES D'AMIDE D'ACIDE 1-SULFONYL-PIPERDINE-3-CARBOXYLIQUE EN TANT QU'INHIBITEURS DE LA 11-BETA-HYDROXYSTEROIDE DEHYDROGENASE POUR LE TRAITEMENT DU DIABETE SUCRE DE TYPE II
  申请人：HOFFMANN LA ROCHE

  公开号：WO2006094633A1

  公开（公告）日：2006-09-14

  [EN] Provided herein are compounds of the formula (I) as well as pharmaceutically acceptable salts thereof, wherein the substituents are as those disclosed in the specification. These compounds, and the pharmaceutical compositions containing them, are useful for the treatment of diseases such as, for example, type II diabetes mellitus and metabolic syndrome.
  [FR] L'invention fournit ici des composés répondant à la formule (I) ainsi que des sels de ceux-ci acceptables sur le plan pharmaceutique, les substituants étant ceux décrits dans le mémoire descriptif. Ces composés, et les compositions pharmaceutiques les contenant, sont utiles pour le traitement de maladies telles que, par exemple, le diabète sucré de type II et le syndrome métabolique.
• Synthesis and Evaluation of Benzothiazole-Based Analogues as Novel, Potent, and Selective Fatty Acid Amide Hydrolase Inhibitors
  作者：Xueqing Wang、Katerina Sarris、Karen Kage、Di Zhang、Scott P. Brown、Teodozyi Kolasa、Carol Surowy、Odile F. El Kouhen、Steven W. Muchmore、Jorge D. Brioni、Andrew O. Stewart

  DOI：10.1021/jm801042a

  日期：2009.1.8

  High-throughput screening (HTS) identified benzothiazole analogue 3 as a potent fatty acid amide hydrolase (FAAH) inhibitor. Structure-activity relationship (SAR) studies indicated that the sulfonyl group, the piperidine ring and benzothiazole were the key components to their activity, with 16j being the most potent analogue in this series. Time-dependent preincubation study of compound 3 was consistent with it being a reversible inhibitor. Activity-based protein-profiling (ABPP) evaluation of 3 in rat tissues revealed that it had exceptional selectivity and no off-target activity with respect to other serine hydrolases. Molecular shape overlay of 3 with a known FAAH inhibitor indicated that these compounds might act as transition-state analogues, forming putative hydrogen bonds with catalytic residues and mimicking the charge distribution of the tetrahedral transition state. The modeling study also indicated that hydrophobic interactions of the benzothiazole ring with the enzyme contributed to its extraordinary potency. These compounds may provide useful tools for the study of FAAH and the endocannabinoid system.