2-(4-bromo-3-fluorophenyl)-1,3-dioxane | 1202075-51-1

• 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: 2-(4-bromo-3-fluorophenyl)-1,3-dioxane
• CAS: 1202075-51-1
• 化学式: C₁₀H₁₀BrFO₂
• 分子量: 261.091
• InChiKey: JGKJWBWPTVSYKS-UHFFFAOYSA-N

物化性质

• 沸点：
  298.3±40.0 °C(Predicted)
• 密度：
  1.508±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  14
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  18.5
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-(4-bromo-3-fluorophenyl)-1,3-dioxane 在 盐酸 、 正丁基锂 、 二氯双[二叔丁基-(4-二甲基氨基苯基)膦]钯(II) 、 potassium tert-butylate 、 三甲基碘化亚砜 、 sodium carbonate 、 potassium carbonate 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 水 、 二甲基亚砜 、 N,N-二甲基甲酰胺 为溶剂， 生成 3-fluoro-4-(5-(1-phenylcyclopropyl)thiazolo[5,4-b]pyridin-2-yl)benzaldehyde
  参考文献：
  名称：

  Discovery of AMG 369, a Thiazolo[5,4-b]pyridine Agonist of S1P₁ and S1P₅

  摘要：

  The optimization of a series of thiazolopyridine S1P(1) agonists with limited activity, at the S1P(3) receptor is reported. These efforts resulted in the discovery of 1-(3-fluoro-4-(5-(1-phenylcycloprol)thiazolo[5,4-b]pyridin-2yl)benzyl)-azetidine-3-carboxylic acid (5d, AMG 369), a potent dual S1P(1)/S1P(5) agonist with limited activity at S1P(3) and no activity at S1P(2)/S1P(4). Dosed orally at 0.1 mg/kg, 5d is shown to reduce blood lymphocyte counts 24 h postdose and delay the onset and reduce the severity of experimental autoimmune encephalomyelitis in rat.

  DOI：

  10.1021/ml100306h
• 作为产物：
  描述：

  4-溴-3-氟苯甲醛 、 1,3-丙二醇 、 对甲苯磺酸一水合物 在 solvent 、 碳酸氢钠 、 magnesium sulfate 作用下， 以 甲苯 为溶剂， 以to give 2-(4-bromo-3-fluorophenyl)-1,3-dioxane as a white solid的产率得到2-(4-bromo-3-fluorophenyl)-1,3-dioxane
  参考文献：
  名称：

  S1P1 receptor agonists and use thereof

  摘要：

  本发明涉及式（I）的化合物：具有S1P受体调节剂活性，更具体地说，是S1P1受体激动剂的化合物。本发明还涉及使用这些化合物治疗与不适当的S1P1受体活性相关的疾病，如自身免疫疾病。

  公开号：

  US07842685B2

文献信息

• [EN] S1P1 RECEPTOR AGONISTS AND USE THEREOF<br/>[FR] AGONISTES DU RÉCEPTEUR S1P1 ET UTILISATIONS
  申请人：AMGEN INC

  公开号：WO2009154775A1

  公开（公告）日：2009-12-23

  The present invention relates to compounds of Formula (I), that have activity as S1P receptor modulating agents, more specifically to specifically compounds that are S1P1 receptor agonists. The invention also related to the use of such compounds to treat diseases associated with inappropriate S1P1 receptor activity such as autoimmune diseases.

  本发明涉及公式（I）的化合物，该化合物具有作为S1P受体调节剂的活性，更具体地说，是具有S1P1受体激动剂活性的化合物。本发明还涉及使用这种化合物来治疗与不适当的S1P1受体活性相关的疾病，如自身免疫性疾病。
• S1P1 RECEPTOR AGONISTS AND USE THEREOF
  申请人：Cee Victor J.

  公开号：US20120129828A1

  公开（公告）日：2012-05-24

  The present invention relates to compounds of Formula (I) that are have activity as S1P1 receptor modulating agents, more specifically to specifically compounds that are S1P1 receptor agonists. The invention also related to the use of such compounds to treat diseases associated with inappropriate S1P1 receptor activity such as autoimmune diseases.

  本发明涉及一些化合物的式（I），这些化合物具有作为S1P1受体调节剂的活性，更具体地说，是S1P1受体激动剂的化合物。本发明还涉及使用这些化合物来治疗与不适当的S1P1受体活性相关的疾病，如自身免疫疾病。
• Novel 5- and 6-subtituted benzothiazoles with improved physicochemical properties: Potent S1P1 agonists with in vivo lymphocyte-depleting activity
  作者：Mike Frohn、Victor J. Cee、Brian A. Lanman、Alexander J. Pickrell、Jennifer Golden、Dalia Rivenzon-Segal、Scot Middleton、Mike Fiorino、Han Xu、Michael Schrag、Yang Xu、Michele McElvain、Kristine Muller、Jerry Siu、Roland Bürli

  DOI：10.1016/j.bmcl.2011.10.069

  日期：2012.1

  An SAR campaign designed to increase polarity in the 'tail' region of benzothiazole 1 resulted in two series of structurally novel 5- and 6-substituted S1P(1) agonists. Structural optimization for potency ultimately delivered carboxamide (+)-11f, which in addition to possessing improved physicochemical properties relative to starting benzothiazole 1, also displayed good S1P(3) selectivity and acceptable in vivo lymphocyte-depleting activity. (C) 2011 Published by Elsevier Ltd.
• Discovery of a Potent, S1P₃-Sparing Benzothiazole Agonist of Sphingosine-1-Phosphate Receptor 1 (S1P₁)
  作者：Brian A. Lanman、Victor J. Cee、Srinivasa R. Cheruku、Mike Frohn、Jennifer Golden、Jian Lin、Mercedes Lobera、Yael Marantz、Kristine M. Muller、Susana C. Neira、Alexander J. Pickrell、Dalia Rivenzon-Segal、Nili Schutz、Anurag Sharadendu、Xiang Yu、Zhaoda Zhang、Janet Buys、Mike Fiorino、Anu Gore、Michelle Horner、Andrea Itano、Michele McElvain、Scot Middleton、Michael Schrag、Hugo M. Vargas、Han Xu、Yang Xu、Xuxia Zhang、Jerry Siu、Roland W. Bürli

  DOI：10.1021/ml100228m

  日期：2011.2.10

  Optimization of a benzofuranyl SIP, agonist lead compound (3) led to the discovery of 1-(3-fluoro-4-(5-(2-fluorobenzyl)benzo[d]thiazol-2-yl)benzyl)-azetidine-3-carboxylic acid (14), a potent SIP, agonist with minimal activity at S1P(3). Dosed orally at 0.3 mg/kg, 14 significantly reduced blood lymphocyte counts 24 h postdose and attenuated a delayed type hypersensitivity (DTH) response to antigen challenge.
• US7842685B2
  申请人：——

  公开号：US7842685B2

  公开（公告）日：2010-11-30