(S)-5-cyano-2-((1,1,1-trifluoropropan-2-yl)oxy)benzoic acid | 1421938-50-2

• 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: (S)-5-cyano-2-((1,1,1-trifluoropropan-2-yl)oxy)benzoic acid
• 英文别名: 5-cyano-2-[(2S)-1,1,1-trifluoropropan-2-yl]oxybenzoic acid
• CAS: 1421938-50-2
• 化学式: C₁₁H₈F₃NO₃
• 分子量: 259.185
• InChiKey: JBDQLLDFSMAHBT-LURJTMIESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  18
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  70.3
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  (S)-5-cyano-2-((1,1,1-trifluoropropan-2-yl)oxy)benzoic acid 、 2-(5-fluoropyridin-3-yl)-2,4,5,6-tetrahydropyrrolo[3,4-c]pyrazole 在 三乙胺 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 5.0h， 以44%的产率得到3-[2-(5-fluoropyridin-3-yl)-2H,4H,5H,6H-pyrrolo[3,4-c]pyrazol-5-carbonyl]-4-{[(2S)-1,1,1-trifluoropropan-2-yl]oxy}benzonitrile
  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：

  (2S)-1,1,1-三氟丙烷-2-醇 、 5-氰基-2-氟苯甲酸 在 caesium carbonate 作用下， 以 1,4-二氧六环 为溶剂， 反应 23.0h， 以84%的产率得到(S)-5-cyano-2-((1,1,1-trifluoropropan-2-yl)oxy)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

• Phenyl-3-aza-bicyclo[3.1.0]hex-3-yl-methanones and the use thereof as medicament
  申请人：GIOVANNINI Riccardo

  公开号：US20130197011A1

  公开（公告）日：2013-08-01

  Substituted phenyl-3-aza-bicyclo[3.1.0]hex-3-yl-methanones which are glycine transporter-1 (GlyT1) inhibitors. These are useful for the treatment of schizophrenia, Alzheimer's Disease and other neurological and psychiatric disorders.

  取代苯基-3-氮杂双环[3.1.0]己-3-基甲酮是甘氨酸转运蛋白-1（GlyT1）抑制剂。这些化合物对治疗精神分裂症、阿尔茨海默病和其他神经系统和精神疾病有用。
• PHENYL-3-AZA-BICYCLO[3.1.0]HEX-3-YL-METHANONES AND THE USE THEREOF AS MEDICAMENT
  申请人：Boehringer Ingelheim International GmbH

  公开号：EP2739615B1

  公开（公告）日：2017-03-15
• US9012489B2
  申请人：——

  公开号：US9012489B2

  公开（公告）日：2015-04-21
• Design and Synthesis of Novel and Selective Glycine Transporter-1 (GlyT1) Inhibitors with Memory Enhancing Properties
  作者：Vincent J. Santora、Theresa A. Almos、Richard Barido、Jillian Basinger、Chris L. Bellows、Brett C. Bookser、J. Guy Breitenbucher、Nicola J. Broadbent、Clifford Cabebe、Chih-Kun Chai、Mi Chen、Stephine Chow、De Michael Chung、Lindsay Crickard、Anne M. Danks、Graeme C. Freestone、Dany Gitnick、Varsha Gupta、Christine Hoffmaster、Andrew R. Hudson、Alan P. Kaplan、Michael R. Kennedy、Dong Lee、James Limberis、Kiev Ly、Chi Ching Mak、Brittany Masatsugu、Andrew C. Morse、Jim Na、David Neul、John Nikpur、Marco Peters、Robert E. Petroski、Joel Renick、Kristen Sebring、Samantha Sevidal、Ali Tabatabaei、Jenny Wen、Yingzhuo Yan、Zachary W. Yoder、Douglas Zook

  DOI：10.1021/acs.jmedchem.8b00372

  日期：2018.7.26

  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.