6-amino-5-fluoro-3,4-dihydronaphthalen-1(2H)-one | 939043-54-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 四氢化萘
• 英文名称: 6-amino-5-fluoro-3,4-dihydronaphthalen-1(2H)-one
• 英文别名: 6-amino-5-fluoro-tetralone；6-amino-5-fluoro-3,4-dihydro-1(2H)-naphthalenone；6-amino-5-fluoro-3,4-dihydro-2H-naphthalen-1-one
• CAS: 939043-54-6
• 化学式: C₁₀H₁₀FNO
• 分子量: 179.194
• InChiKey: HEAIGSZQOAYQCW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  13
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  43.1
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  6-amino-5-fluoro-3,4-dihydronaphthalen-1(2H)-one 在 吡啶 、 盐酸 、 20 % Pd(OH)2/C 、 硼烷 、 盐酸羟胺 、 ammonium acetate 、 氢气 、 caesium carbonate 、 N,N-二异丙基乙胺 、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 、 碘甲烷 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 、 二氯甲烷 、 水 、 乙腈 为溶剂， 生成 2-(5-chlorothiophen-2-yl)-N-[(3S)-1-(6-fluoro-2,3,4,5-tetrahydro-1H-2-benzazepin-7-yl)-2-oxopyrrolidin-3-yl]ethenesulfonamide
  参考文献：
  名称：

  The discovery of potent and long-acting oral factor Xa inhibitors with tetrahydroisoquinoline and benzazepine P4 motifs

  摘要：

  The discovery and evaluation of potent and long-acting oral sulfonamidopyrrolidin-2-one factor Xa inhibitors with tetrahydroisoquinoline and benzazepine P4 motifs are described. Unexpected selectivity issues versus tissue plasminogen activator in the former series were addressed in the later, delivering a robust candidate for progression towards clinical studies. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.01.129
• 作为产物：
  描述：

  2,3-二氟溴苯 在 bis-triphenylphosphine-palladium(II) chloride 、 copper(l) iodide 、 甲烷磺酸 、 四磷十氧化物 、 20 % Pd(OH)2/C 、 氨 、 氢气 、 二甲胺 、 pyridinium chlorochromate 作用下， 以 甲醇 、 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 20.0~160.0 ℃ 、344.75 kPa 条件下， 生成 6-amino-5-fluoro-3,4-dihydronaphthalen-1(2H)-one
  参考文献：
  名称：

  The discovery of potent and long-acting oral factor Xa inhibitors with tetrahydroisoquinoline and benzazepine P4 motifs

  摘要：

  The discovery and evaluation of potent and long-acting oral sulfonamidopyrrolidin-2-one factor Xa inhibitors with tetrahydroisoquinoline and benzazepine P4 motifs are described. Unexpected selectivity issues versus tissue plasminogen activator in the former series were addressed in the later, delivering a robust candidate for progression towards clinical studies. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.01.129

文献信息

• 1-Benzazepine-3-Sulfonylamino-2-Pyrroridones as Factor Xa Inhibitors
  申请人：Camus Laure

  公开号：US20080306045A1

  公开（公告）日：2008-12-11

  The invention relates to chemical entities of formula (I): and/or pharmaceutically acceptable derivative(s) thereof. The invention also relates to processes for the preparation of compounds of formula (I), pharmaceutical compositions containing compounds of formula (I) and to the use of compounds of formula (I) in medicine, particularly in the amelioration of a clinical condition for which a Factor Xa inhibitor is indicated.

  该发明涉及式(I)的化学实体和/或其药用可接受衍生物。该发明还涉及制备式(I)化合物的方法，含有式(I)化合物的药物组合物以及在医学中使用式(I)化合物，特别是在改善适用于Xa因子抑制剂的临床病况中的使用。
• Design, synthesis, and pharmacological evaluation of N-bicyclo-5-chloro-1H-indole-2-carboxamide derivatives as potent glycogen phosphorylase inhibitors
  作者：Kenichi Onda、Ryota Shiraki、Takashi Ogiyama、Kazuhiro Yokoyama、Kazuhiro Momose、Naoko Katayama、Masaya Orita、Tomohiko Yamaguchi、Masako Furutani、Noritaka Hamada、Makoto Takeuchi、Minoru Okada、Mitsuaki Ohta、Shin-ichi Tsukamoto

  DOI：10.1016/j.bmc.2008.10.021

  日期：2008.12

  As a result of the various N-bicyclo-5-chloro-1H-indole-2-carboxamide derivatives with a hydroxy moiety synthesized in an effort to discover novel glycogen phosphorylase (GP) inhibitors, 5-chloro-N-(5-hydroxy-5,6,7,8-tetrahydronaphthalen-2-yl)-1H-indole-2-carboxamide (5b) was found to have potent inhibitory activity. The introduction of fluorine atoms both at a position adjacent to the hydroxy group and in the central benzene moiety lead to the optically active derivative 5-chloro-N-[(5R)-1,3,6,6-tetrafluoro-5-hydroxy-5,6,7,8-tetrahydronaphthalen-2-yl]-1H-indole-2-carboxamide(25e alpha, which was the most potent compound in this series (IC(50) = 0.020 mu M). This compound inhibited glucagon-induced glucose output in cultured primary hepatocytes with an IC(50) value of 0.69 mu M, and showed oral hypoglycemic activity in diabetic db/db mice at 10 mg/kg. Compound 25e alpha also had an excellent pharmacokinetic profile, with high oral bioavailability and a long plasma half-life, in male SD rats. The binding mode of 25e alpha to this molecule and the role of fluorine atoms in that binding were speculated in an enzyme docking study. (c) 2008 Elsevier Ltd. All rights reserved.
• CHEMICAL COMPOUNDS
  申请人：GLAXO GROUP LIMITED

  公开号：EP1951712A2

  公开（公告）日：2008-08-06
• [EN] CHEMICAL COMPOUNDS<br/>[FR] COMPOSÉS CHIMIQUES
  申请人：GLAXO GROUP LTD

  公开号：WO2007059952A2

  公开（公告）日：2007-05-31

  [EN] The invention relates to chemical entities of formula (I): and/or pharmaceutically acceptable derivative(s) thereof. The invention also relates to processes for the preparation of compounds of formula (I), pharmaceutical compositions containing compounds of formula (I) and to the use of compounds of formula (I) in medicine, particularly in the amelioration of a clinical condition for which a Factor Xa inhibitor is indicated.
  [FR] La présente invention concerne des entités chimiques de formule (I) : et/ou un ou plusieurs dérivés de qualité pharmaceutique desdites entités. La présente invention concerne également des procédés de synthèse des composés de formule (I), des préparations pharmaceutiques contenant les composés de formule (I) et l'emploi des composés de formule (I) en médecine, en particulier pour le soulagement d'un état pathologique clinique pour lequel est indiquée l'utilisation d'un inhibiteur du Facteur Xa.
• The discovery of potent and long-acting oral factor Xa inhibitors with tetrahydroisoquinoline and benzazepine P4 motifs
  作者：Nigel S. Watson、Carl Adams、David Belton、David Brown、Cynthia L. Burns-Kurtis、Laiq Chaudry、Chuen Chan、Máire A. Convery、David E. Davies、Anne M. Exall、John D. Harling、Stephanie Irvine、Wendy R. Irving、Savvas Kleanthous、Iain M. McLay、Anthony J. Pateman、Angela N. Patikis、Theresa J. Roethke、Stefan Senger、Gary J. Stelman、John R. Toomey、Robert I. West、Caroline Whittaker、Ping Zhou、Robert J. Young

  DOI：10.1016/j.bmcl.2011.01.129

  日期：2011.3

  The discovery and evaluation of potent and long-acting oral sulfonamidopyrrolidin-2-one factor Xa inhibitors with tetrahydroisoquinoline and benzazepine P4 motifs are described. Unexpected selectivity issues versus tissue plasminogen activator in the former series were addressed in the later, delivering a robust candidate for progression towards clinical studies. (C) 2011 Elsevier Ltd. All rights reserved.