N-{(3S,4S)-4-[(2'-cyano-4'-fluorobiphenyl-4-yl)oxy]tetrahydrofuran-3-yl}propane-2-sulfonamide | 1258963-76-6

• 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: N-{(3S,4S)-4-[(2'-cyano-4'-fluorobiphenyl-4-yl)oxy]tetrahydrofuran-3-yl}propane-2-sulfonamide
• 英文别名: N-[(3S,4S)-4-[4-(2-cyano-4-fluorophenyl)phenoxy]oxolan-3-yl]propane-2-sulfonamide
• CAS: 1258963-76-6
• 化学式: C₂₀H₂₁FN₂O₄S
• 分子量: 404.462
• InChiKey: AYXREMJTAZQOHI-VQTJNVASSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  28
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  96.8
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  trans-4-(4-bromophenoxy)tetrahydrofuran-3-yl methanesulfonate 在 potassium fluoride 、 ammonium hydroxide 、 palladium diacetate 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 、 2-二环己基磷-2,4,6-三异丙基联苯 作用下， 以 甲醇 、 正庚烷 、 二氯甲烷 、 二乙胺 、 异丙醇 、 甲苯 为溶剂， 反应 20.5h， 生成 N-{(3S,4S)-4-[(2'-cyano-4'-fluorobiphenyl-4-yl)oxy]tetrahydrofuran-3-yl}propane-2-sulfonamide
  参考文献：
  名称：

  The Discovery and Characterization of the α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid (AMPA) Receptor Potentiator N-{(3S,4S)-4-[4-(5-Cyano-2-thienyl)phenoxy]tetrahydrofuran-3-yl}propane-2-sulfonamide (PF-04958242)

  摘要：

  A unique tetrahydrofuran ether class of highly potent alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor potentiators has been identified using rational and structure-based drug design. An acyclic lead compound, containing an ether-linked isopropylsulfonamide and biphenyl group, was pharmacologically augmented by converting it to a conformationally constrained tetrahydrofuran to improve key interactions with the human GluA2 ligand-binding domain. Subsequent replacement of the distal phenyl motif with 2-cyanothiophene to enhance its potency, selectivity, and metabolic stability afforded N-{(3S,4S)-4-[4-(5-cyano-2-thienyl)-phenoxy]tetrahydrofuran-3-yl}propane-2-sulfonamide (PF-04958242, 3), whose preclinical characterization suggests an adequate therapeutic index, aided by low projected human oral pharmacokinetic variability, for clinical studies exploring its ability to attenuate cognitive deficits in patients with schizophrenia.

  DOI：

  10.1021/acs.jmedchem.5b00300

文献信息

• [EN] HETEROCYCLIC SULFONAMIDES, USES AND PHARMACEUTICAL COMPOSITIONS THEREOF<br/>[FR] SULFONAMIDES HÉTÉROCYCLIQUES, UTILISATIONS ET COMPOSITIONS PHARMACEUTIQUES ASSOCIÉES
  申请人：PFIZER

  公开号：WO2010150192A1

  公开（公告）日：2010-12-29

  The invention is directed to a class of compounds, including the pharmaceutically acceptable salts of the compounds, having the structure of formula (I) as defined in the specification. The invention is also directed to compositions containing and uses of the compounds of formula I.

  该发明涉及一类化合物，包括该化合物的药用可接受盐，其具有规范中定义的式(I)的结构。该发明还涉及含有和使用式I化合物的组合物。
• Heterocyclic Sulfonamides, Uses and Pharmaceutical Compositions Thereof
  申请人：Fliri Anton F. J.

  公开号：US20110105533A1

  公开（公告）日：2011-05-05

  The invention is directed to a class of compounds, including the pharmaceutically acceptable salts of the compounds, having the structure of formula I: as defined in the specification. The invention is also directed to compositions containing and uses of the compounds of formula I.

  本发明涉及一类化合物，包括化合物的药用可接受盐，其结构如式I所定义。本发明还涉及含有式I化合物的组合物和其用途。
• HETEROCYCLIC SULFONAMIDES, USES AND PHARMACEUTICAL COMPOSITIONS THEREOF
  申请人：Fliri Anton F. J.

  公开号：US20120322823A1

  公开（公告）日：2012-12-20

  The invention is directed to a class of compounds, including the pharmaceutically acceptable salts of the compounds, having the structure of formula I: as defined in the specification. The invention is also directed to compositions containing and uses of the compounds of formula I.

  本发明涉及一类化合物，包括化合物的药学上可接受的盐，其结构如公式I所定义。本发明还涉及含有公式I化合物的组合物和其用途。
• US8278457B2
  申请人：——

  公开号：US8278457B2

  公开（公告）日：2012-10-02
• The Discovery and Characterization of the α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid (AMPA) Receptor Potentiator <i>N</i>-{(3<i>S</i>,4<i>S</i>)-4-[4-(5-Cyano-2-thienyl)phenoxy]tetrahydrofuran-3-yl}propane-2-sulfonamide (PF-04958242)
  作者：Christopher L. Shaffer、Nandini C. Patel、Jacob Schwarz、Renato J. Scialis、Yunjing Wei、Xinjun J. Hou、Longfei Xie、Kapil Karki、Dianne K. Bryce、Sarah M. Osgood、William E. Hoffmann、John T. Lazzaro、Cheng Chang、Dina F. McGinnis、Susan M. Lotarski、JianHua Liu、R. Scott Obach、Mark L. Weber、Laigao Chen、Kenneth R. Zasadny、Patricia A. Seymour、Christopher J. Schmidt、Mihály Hajós、Raymond S. Hurst、Jayvardhan Pandit、Christopher J. O’Donnell

  DOI：10.1021/acs.jmedchem.5b00300

  日期：2015.5.28

  A unique tetrahydrofuran ether class of highly potent alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor potentiators has been identified using rational and structure-based drug design. An acyclic lead compound, containing an ether-linked isopropylsulfonamide and biphenyl group, was pharmacologically augmented by converting it to a conformationally constrained tetrahydrofuran to improve key interactions with the human GluA2 ligand-binding domain. Subsequent replacement of the distal phenyl motif with 2-cyanothiophene to enhance its potency, selectivity, and metabolic stability afforded N-(3S,4S)-4-[4-(5-cyano-2-thienyl)-phenoxy]tetrahydrofuran-3-yl}propane-2-sulfonamide (PF-04958242, 3), whose preclinical characterization suggests an adequate therapeutic index, aided by low projected human oral pharmacokinetic variability, for clinical studies exploring its ability to attenuate cognitive deficits in patients with schizophrenia.