3-fluoro-4-(5-(1-phenylcyclopropyl)thiazolo[5,4-b]pyridin-2-yl)benzaldehyde | 1202075-59-9

• 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: 3-fluoro-4-(5-(1-phenylcyclopropyl)thiazolo[5,4-b]pyridin-2-yl)benzaldehyde
• 英文别名: 3-fluoro-4-[5-(1-phenylcyclopropyl)-[1,3]thiazolo[5,4-b]pyridin-2-yl]benzaldehyde
• CAS: 1202075-59-9
• 化学式: C₂₂H₁₅FN₂OS
• 分子量: 374.438
• InChiKey: GIHSRFKFTOSKQX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.1
• 重原子数：
  27
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  71.1
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  3-fluoro-4-(5-(1-phenylcyclopropyl)thiazolo[5,4-b]pyridin-2-yl)benzaldehyde 在 sodium tetrahydroborate 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 2.0h， 以75%的产率得到(3-Fluoro-4-(5-(1-phenylcyclopropyl)thiazolo[5,4-b]pyridin-2-yl)phenyl)methanol
  参考文献：
  名称：

  Isoform-selective thiazolo[5,4-b]pyridine S1P1 agonists possessing acyclic amino carboxylate head-groups

  摘要：

  Replacement of the azetidine carboxylate of an S1P(1) agonist development candidate, AMG 369, with a range of acyclic head-groups led to the identification of a novel, S1P(3)-sparing S1P(1) agonist, ( )-2-amino -4-(3-fluoro-4-(5-(1-phenylcyclopropyl)thiazolo[5,4-b]pyridin-2-yl)phenyl)-2-methylbutanoic acid (8c), which possessed good in vivo efficacy and pharmacokinetic properties. A 0.3 mg/kg oral dose of 8c produced a statistically significant reduction in blood lymphocyte counts 24 h post-dosing in female Lewis rats. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.12.073
• 作为产物：
  描述：

  2-(4-(1,3-Dioxan-2-yl)-2-fluorophenyl)-5-(1-phenylcyclopropyl)thiazolo[5,4-b]pyridine 在 盐酸 作用下， 以 四氢呋喃 、 水 为溶剂， 以93%的产率得到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

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：US20100029611A1

  公开（公告）日：2010-02-04

  The present invention relates to compounds of Formula (I): that are 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.

  本发明涉及式（I）的化合物：具有S1P受体调节剂活性，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，如自身免疫性疾病。
• S1P1 RECEPTOR AGONISTS AND USE THEREOF
  申请人：Amgen, Inc

  公开号：EP2306994A1

  公开（公告）日：2011-04-13
• US7842685B2
  申请人：——

  公开号：US7842685B2

  公开（公告）日：2010-11-30
• Isoform-selective thiazolo[5,4-b]pyridine S1P1 agonists possessing acyclic amino carboxylate head-groups
  作者：Anthony B. Reed、Brian A. Lanman、Susana Neira、Paul E. Harrington、Kelvin K.C. Sham、Mike Frohn、Alexander J. Pickrell、Andrew S. Tasker、Anu Gore、Mike Fiorino、Andrea Itano、Michele McElvain、Scot Middleton、Henry Morrison、Han Xu、Yang Xu、Min Wong、Victor J. Cee

  DOI：10.1016/j.bmcl.2011.12.073

  日期：2012.2

  Replacement of the azetidine carboxylate of an S1P(1) agonist development candidate, AMG 369, with a range of acyclic head-groups led to the identification of a novel, S1P(3)-sparing S1P(1) agonist, ( )-2-amino -4-(3-fluoro-4-(5-(1-phenylcyclopropyl)thiazolo[5,4-b]pyridin-2-yl)phenyl)-2-methylbutanoic acid (8c), which possessed good in vivo efficacy and pharmacokinetic properties. A 0.3 mg/kg oral dose of 8c produced a statistically significant reduction in blood lymphocyte counts 24 h post-dosing in female Lewis rats. (C) 2011 Elsevier Ltd. All rights reserved.