1-(噻吩-2-基磺酰基)哌啶-4-羧酸 | 327971-19-7

• 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: 1-(噻吩-2-基磺酰基)哌啶-4-羧酸
• 英文名称: 1-(thiophen-2-ylsulfonyl)piperidine-4-carboxylic acid
• 英文别名: 1-(thiophene-2-sulfonyl)-piperidine-4-carboxylic acid；1-thiophen-2-ylsulfonylpiperidine-4-carboxylic acid
• CAS: 327971-19-7
• 化学式: C₁₀H₁₃NO₄S₂
• mdl: MFCD01925604
• 分子量: 275.35
• InChiKey: UHLPQMBGBPAJFX-UHFFFAOYSA-N

物化性质

• 沸点：
  485.7±55.0 °C(Predicted)
• 密度：
  1.476±0.06 g/cm3(Predicted)
• 溶解度：
  >41.3 [ug/mL]

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
• 海关编码：
  2934999090

反应信息

• 作为反应物：
  描述：

  1-(噻吩-2-基磺酰基)哌啶-4-羧酸 、 4-(2-苯并噻唑基)苯胺 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77%的产率得到N-(4-(benzo[d]thiazol-2-yl)phenyl)-1-(thiophen-2-ylsulfonyl)piperidine-4-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：

  1-(噻吩-2-磺酰基)-哌啶-4-羧酸乙酯 在 氢氧化钾 、 水 、 盐酸 作用下， 以 乙醇 、 水 为溶剂， 反应 4.5h， 生成 1-(噻吩-2-基磺酰基)哌啶-4-羧酸
  参考文献：
  名称：

  WO2007/144394

  摘要：

  公开号：

文献信息

• Total Synthesis of 7-Ethyl-10-hydroxycamptothecin (SN38) and its Application to the Development of C18-Functionalized Camptothecin Derivatives
  作者：Yuan-Shan Yao、Jia-Li Liu、Jie Xi、Bukeyan Miu、Guai-Sai Liu、Shaozhong Wang、Linghua Meng、Zhu-Jun Yao

  DOI：10.1002/chem.201101389

  日期：2011.9.5

  N‐acyliminium intermediate with a silyl enol ether. An intramolecular oxa Diels–Alder reaction efficiently constructed the D and E rings in one step. Successive asymmetric dihydroxylation and I2‐based hemiacetal oxidation furnished the stereochemistry of SN38 with high enantiopurity. Utilizing the ABC‐ring intermediate and a functionalized silyl enol ether permitted the synthesis of a number of new C18‐functionalized

  喜树碱前药伊立替康的活性代谢产物SN38的新化学合成已通过简单的市售起始原料实现了12个步骤。温和有效的FeCl 3催化的Friedländer缩合成功地用于构建AB环系统。C环的官能化通过的原位产生的N一插烯向山反应完成- acyliminium中间体与甲硅烷基烯醇醚。分子内氧杂Diels-Alder反应可一步有效地构建D和E环。连续不对称二羟基化和I 2基于半缩醛的氧化使SN38的立体化学具有很高的对映体纯度。利用ABC环中间体和官能化的甲硅烷基烯醇醚可以合成许多新的C18官能化的SN38衍生物。发现带有C 10甲氧基的几种新颖的SN38衍生物相对于SN38表现出可比的或更有效的抑制癌细胞增殖的活性。
• PHARMACEUTICAL USE OF SUBSTITUTED PIPERIDINE CARBOXAMIDES
  申请人：Kilburn John Paul

  公开号：US20090306048A1

  公开（公告）日：2009-12-10

  A novel class of compounds of the general formula (I), their use in therapy, pharmaceutical compositions comprising the compounds, as well as their use in the manufacture of medicaments are described. The present compounds modulate the activity of 11β-hydroxysteroid dehydrogenase type 1 (11βHSD1) and are accordingly useful in the treatment of diseases in which such a modulation is beneficial, e.g. the metabolic syndrome.

  本文描述了一类新型化合物的一般式（I），它们在治疗中的应用，包括这些化合物的制药组合物以及它们在药物制造中的应用。这些化合物调节11β-羟基类固醇脱氢酶1（11βHSD1）的活性，因此在治疗这种调节有益的疾病（例如代谢综合症）中有用。
• ACTIVATORS OF LATERAL ROOT FORMATION
  申请人：Audenaert Dominique

  公开号：US20100105561A1

  公开（公告）日：2010-04-29

  The present invention relates to small chemical compounds that act as activators of lateral root formation in plants. More specifically, it relates to small chemical compounds that are structurally not related to auxin but do have a similar effect on root density development in plants. Preferably, these compounds act more specifically on root development than auxin, and may have a different working mechanism.
• [EN] PHARMACEUTICAL USE OF SUBSTITUTED PIPERIDINE CARBOXAMIDES<br/>[FR] UTILISATION PHARMACEUTIQUE DE CARBOXAMIDES DE PIPÉRIDINE SUBSTITUÉS
  申请人：NOVO NORDISK AS

  公开号：WO2007144394A2

  公开（公告）日：2007-12-21

  [EN] A novel class of compounds of the general formula (I) and (Ia), their use in therapy, pharmaceutical compositions comprising the compounds, as well as their use in the manufacture of medicaments are described. The present compounds modulate the activity of 11ß- hydroxysteroid dehydrogenase type 1 (11ßHSD1) and are accordingly useful in the treatment of diseases in which such a modulation is beneficial, e.g. the metabolic syndrome.
  [FR] La présente invention concerne une nouvelle classe de composés de formule générale (I) et (Ia), leur utilisation en thérapie, des compositions pharmaceutiques comprenant les composés, ainsi que leur utilisation dans la fabrication de médicaments. Les présents composés modulent l'activité de la 11ß-hydroxystéroïde déshydrogénase de type 1 (11ßHSD1) et sont en conséquence utiles dans le traitement de maladies dans lesquelles une telle modulation est bénéfique, par exemple, 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.