2-(4,4-difluoropiperidin-1-yl)-5-(methylsulfonyl)benzoic acid

• 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: 2-(4,4-difluoropiperidin-1-yl)-5-(methylsulfonyl)benzoic acid
• 英文别名: 2-(4,4-difluoro-1-piperidinyl)-5-(methylsulfonyl)benzoic acid；2-(4,4-difluoropiperidin-1-yl)-5-methylsulfonylbenzoic acid
• 化学式: C₁₃H₁₅F₂NO₄S
• 分子量: 319.329
• InChiKey: LNGKXHGHLWDKLX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  21
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  83.1
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  2-(4,4-difluoropiperidin-1-yl)-5-(methylsulfonyl)benzoic acid 在 氯化亚砜 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 3.92h， 生成 4,4-difluoro-1-{2-[2-(2-fluorophenyl)-2H,4H,5H,6H-pyrrolo[3,4-c]pyrazole-5-carbonyl]-4-methanesulfonylphenyl}piperidine
  参考文献：
  名称：

  Design and Synthesis of Novel and Selective Glycine Transporter-1 (GlyT1) Inhibitors with Memory Enhancing Properties

  摘要：

  We report here the identification and optimization of a novel series of potent GlyT1 inhibitors. A ligand design campaign that utilized known GlyT1 inhibitors as starting points led to the identification of a novel series of pyrrolo[3,4-c]pyrazoles amides (21-50) with good in vitro potency. Subsequent optimization of physicochemical and in vitro ADME properties produced several compounds with promising pharmacokinetic profiles. In vivo inhibition of GlyT1 was demonstrated for select compounds within this series by measuring the elevation of glycine in the cerebro-spinal fluid (CSF) of rats after a single oral dose of 10 mg/kg. Ultimately, an optimized lead, compound 46, demonstrated in vivo efficacy in a rat novel object recognition (NOR) assay after oral dosing at 0.1, 1, and 3 mg/kg.

  DOI：

  10.1021/acs.jmedchem.8b00372
• 作为产物：
  描述：

  4,4-二氟哌啶 、 2-氟-5-甲烷磺酰基苯甲酸 在 caesium carbonate 作用下， 以 1,4-二氧六环 为溶剂， 反应 23.0h， 以62%的产率得到2-(4,4-difluoropiperidin-1-yl)-5-(methylsulfonyl)benzoic acid
  参考文献：
  名称：

  Design and Synthesis of Novel and Selective Glycine Transporter-1 (GlyT1) Inhibitors with Memory Enhancing Properties

  摘要：

  We report here the identification and optimization of a novel series of potent GlyT1 inhibitors. A ligand design campaign that utilized known GlyT1 inhibitors as starting points led to the identification of a novel series of pyrrolo[3,4-c]pyrazoles amides (21-50) with good in vitro potency. Subsequent optimization of physicochemical and in vitro ADME properties produced several compounds with promising pharmacokinetic profiles. In vivo inhibition of GlyT1 was demonstrated for select compounds within this series by measuring the elevation of glycine in the cerebro-spinal fluid (CSF) of rats after a single oral dose of 10 mg/kg. Ultimately, an optimized lead, compound 46, demonstrated in vivo efficacy in a rat novel object recognition (NOR) assay after oral dosing at 0.1, 1, and 3 mg/kg.

  DOI：

  10.1021/acs.jmedchem.8b00372

文献信息

• Piperazine Derivatives As Glyt 1 Inhibitors
  申请人：Bradley Marcus Daniel

  公开号：US20080090822A1

  公开（公告）日：2008-04-17

  The invention provides a compound of formula (I) or a salt or solvate thereof: wherein R 1 , n, X, Y and Z are as defined in the specification, and uses of such compounds. The compounds inhibit GlyT1 transporters and are useful in the treatment of certain neurological and neuropsychiatric disorders, including schizophrenia.

  该发明提供式（I）的化合物或其盐或溶剂化物：其中R1，n，X，Y和Z如规范中所定义，并提供了这些化合物的用途。这些化合物抑制GlyT1转运体，在治疗某些神经系统和神经精神障碍，包括精神分裂症方面具有用途。
• WO2006/94843
  申请人：——

  公开号：——

  公开（公告）日：——
• PIPERAZINE DERIVATIVES AS GLYT1 INHIBITORS
  申请人：GLAXO GROUP LIMITED

  公开号：EP1856077A1

  公开（公告）日：2007-11-21
• [EN] PIPERAZINE DERIVATIVES AS GLYT1 INHIBITORS<br/>[FR] DÉRIVÉS DE PIPÉRAZINE EN TANT QU'INHIBITEURS DE GLYT1
  申请人：GLAXO GROUP LTD

  公开号：WO2006094843A1

  公开（公告）日：2006-09-14

  [EN] The invention provides a compound of formula (I) or a salt or solvate thereof: wherein R¹, n, X, Y and Z are as defined in the specification, and uses of such compounds. The compounds inhibit GlyT1 transporters and are useful in the treatment of certain neurological and neuropsychiatric disorders, including schizophrenia.
  [FR] L'invention concerne un composé de la formule (I) ou un sel ou un solvate de celui-ci : où R¹, n, X, Y et Z sont tels que définis dans la description, et les utilisations de tels composés. Les composés inhibent les transporteurs de GlyT1 et sont utiles dans le traitement de certains troubles neurologiques et neuropsychiatriques, y compris la schizophrénie.