5-(methylsulfonyl)-2-(neopentyloxy)benzoic acid

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 5-(methylsulfonyl)-2-(neopentyloxy)benzoic acid
• 英文别名: 2-(2,2-dimethyl-propoxy)-5-methanesulfonyl-benzoic acid；2-(2,2-dimethylpropoxy)-5-methylsulfonylbenzoic acid
• 化学式: C₁₃H₁₈O₅S
• 分子量: 286.349
• InChiKey: XEURKSSZVIUMBI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  19
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  89
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  5-(methylsulfonyl)-2-(neopentyloxy)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 5-[2-(2,2-dimethylpropoxy)-5-methanesulfonylbenzoyl]-2-(2-fluorophenyl)-2H,4H,5H,6H-pyrrolo[3,4-c]pyrazole
  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：

  2-氟-5-甲烷磺酰基苯甲酸 、 新戊醇 在 caesium carbonate 作用下， 以 1,4-二氧六环 为溶剂， 反应 23.0h， 以20%的产率得到5-(methylsulfonyl)-2-(neopentyloxy)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

• Heterocyclic-substituted phenyl methanones
  申请人：Jolidon Synese

  公开号：US20060178381A1

  公开（公告）日：2006-08-10

  The present invention relates to compounds of formula I wherein R 1 , R 2 , and are defined in the specification and to pharmaceutically acceptable acid addition salts thereof.

  本发明涉及式I的化合物 其中 R 1 ， R 2 ，并在规范中定义，并且其药学上可接受的酸盐。
• Monocyclic substituted phenyl methanones
  申请人：Jolidon Synese

  公开号：US20060167009A1

  公开（公告）日：2006-07-27

  The present invention relates to compounds of formula I wherein R 1 , R 2 , X 1 , and X 2 are as defined in the specification and to pharmaceutically acceptable acid addition salts thereof. Such compounds are inhibitors of the glycine transporter 1 (GlyT-1) and can be used in the treatment of schizophrenia, cognitive impairment, and Alzheimer's disease.

  本发明涉及公式I的化合物，其中R1，R2，X1和X2的定义如规范中所述，以及其药学上可接受的酸盐。这些化合物是甘氨酸转运体1（GlyT-1）的抑制剂，可用于治疗精神分裂症、认知障碍和阿尔茨海默病。
• HETEROCYCLIC-SUBSTITUTED PHENYL METHANONES
  申请人：Jolidon Synese

  公开号：US20090203665A1

  公开（公告）日：2009-08-13

  The present invention relates to compounds of formula I wherein R 1 , R 2 , and are defined in the specification and to pharmaceutically acceptable acid addition salts thereof.

  本发明涉及式I的化合物，其中R1，R2和在规范中定义，并且其药学上可接受的酸加合盐。
• PIPERAZINE WITH OR-SUBSTITUTED PHENYL GROUP AND THEIR USE AS GLYT1 INHIBITORS
  申请人：F. HOFFMANN-LA ROCHE AG

  公开号：EP1656361B1

  公开（公告）日：2008-01-02
• [4-(HETEROARYL)PIPERAZIN-1-YL]-(2,5-SUBSTITUTED -PHENYL)METHANONE DERIVATIVES AS GLYCINE TRANSPORTER 1 (GLYT-1) INHIBITORS FOR THE TREATMENT OF NEUROLOGICAL AND NEUROPSYCHIATRIC DISORDERS
  申请人：F. Hoffmann-Roche AG

  公开号：EP1838308A1

  公开（公告）日：2007-10-03