N-(2-(4-bromophenoxy)ethyl)propane-2-sulfonamide | 851199-51-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: N-(2-(4-bromophenoxy)ethyl)propane-2-sulfonamide
• 英文别名: SP600125；2-(4-bromo-phenoxy)ethylamine；N-[2-(4-bromophenoxy)ethyl]-2-propanesulfonamide；N-[2-(4-bromophenoxy)ethyl]propane-2-sulfonamide
• CAS: 851199-51-4
• 化学式: C₁₁H₁₆BrNO₃S
• 分子量: 322.223
• InChiKey: QNGCLXXYMFVHHH-UHFFFAOYSA-N

物化性质

• 沸点：
  422.7±51.0 °C(Predicted)
• 密度：
  1.426±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  17
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  63.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  N-(2-(4-bromophenoxy)ethyl)propane-2-sulfonamide 、 2-氰基苯硼酸 在 potassium fluoride 、 palladium diacetate 、 2-二环己基磷-2,4,6-三异丙基联苯 作用下， 以 甲醇 、 甲苯 为溶剂， 反应 0.5h， 以16%的产率得到N-(2-((2'-cyano-[1,1'-biphenyl]-4-yl)oxy)ethyl)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
• 作为产物：
  描述：

  异丙基磺酰氯 、 2-(4-溴苯氧基)乙胺 在 1,8-二氮杂双环[5.4.0]十一碳-7-烯 作用下， 以 二氯甲烷 为溶剂， 以58%的产率得到N-(2-(4-bromophenoxy)ethyl)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] PYRROLE AND PYRAZOLE DERIVATIVES AS POTENTIATORS OF GLUTAMATE RECEPTORS<br/>[FR] COMPOSES DE PYRROLE ET PYRAZOLE PRESENTANT UN EFFET POTENTIATEUR SUR LES RECEPTEURS DU GLUTAMATE
  申请人：LILLY CO ELI

  公开号：WO2005040110A1

  公开（公告）日：2005-05-06

  The present invention relates to pyrrole and pyrazole compounds of formula (I) and their pharmaceutically acceptable salts, and further relates to their use in treating schizophrenia, cognitive deficits associated with schizophrenia, Alzheimer's disease, dementia of the Alzheimer's type, mild cognitive impairment, or depression. The compounds act as potentiators on glutamate receptors, in particular AMPA and the GluR family.

  本发明涉及式(I)的吡咯和吡唑化合物及其药用可接受的盐，并且进一步涉及它们在治疗精神分裂症、与精神分裂症相关的认知缺陷、阿尔茨海默病、阿尔茨海默型痴呆、轻度认知障碍或抑郁症方面的应用。这些化合物作为谷氨酸受体的增强剂，特别是AMPA和GluR家族。
• Pyrrole and pyrazole derivatives as potentiators of glutamate receptors
  申请人：Albaugh Ann Pamela

  公开号：US20070066573A1

  公开（公告）日：2007-03-22

  The present invention relates to pyrrole and pyrazole compounds of formula (I) and their pharmaceutically acceptable salts, and further relates to their use in treating schizophrenia, cognitive deficits associated with schizophrenia, Alzheimer's disease, dementia of the Alzheimer's type, mild cognitive impairment, or depression. The compounds act as potentiators on glutamate receptors, in particular AMPA and the GluR family.

  本发明涉及式(I)的吡咯和吡唑化合物及其药学上可接受的盐，并进一步涉及它们在治疗精神分裂症、与精神分裂症相关的认知缺陷、阿尔茨海默病、阿尔茨海默型痴呆、轻度认知障碍或抑郁症方面的使用。这些化合物在谷氨酸受体上发挥增强剂作用，特别是AMPA和GluR家族。
• PYRROLE AND PYRAZOLE DERIVATIVES AS POTENTIATORS OF GLUTAMATE RECEPTORS
  申请人：ELI LILLY AND COMPANY

  公开号：EP1670757B1

  公开（公告）日：2009-05-06
• US7625932B2
  申请人：——

  公开号：US7625932B2

  公开（公告）日：2009-12-01
• 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.