1-(3-fluoro-4-(5-(1-phenylcyclopropyl)thiazolo[5,4-b]pyridin-2-yl)benzyl)azetidine-3-carboxylic acid | 1202073-26-4

• 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: 1-(3-fluoro-4-(5-(1-phenylcyclopropyl)thiazolo[5,4-b]pyridin-2-yl)benzyl)azetidine-3-carboxylic acid
• 英文别名: AMG 369；1-((3-Fluoro-4-(5-(1-phenylcyclopropyl)thiazolo[5,4-b]pyridin-2-yl)phenyl)methyl)azetidine-3-carboxylic acid；1-[[3-fluoro-4-[5-(1-phenylcyclopropyl)-[1,3]thiazolo[5,4-b]pyridin-2-yl]phenyl]methyl]azetidine-3-carboxylic acid
• CAS: 1202073-26-4
• 化学式: C₂₆H₂₂FN₃O₂S
• 分子量: 459.544
• InChiKey: KCMALGDZUKTGJR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  33
• 可旋转键数：
  6
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  94.6
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  1-(3-fluoro-4-(5-(1-phenylcyclopropyl)thiazolo[5,4-b]pyridin-2-yl)benzyl)azetidine-3-carboxylic acid 在 硫酸 作用下， 以 醋酸异丙酯 、 溶剂黄146 为溶剂， 生成
  参考文献：
  名称：

  Development of a Suitable Physical Form for a Sphingosine-1-phosphate Receptor Agonist

  摘要：

  AMG 369 (1), a novel SIP, agonist, was selected for clinical development for the treatment of multiple sclerosis. Form B of the zwitterionic molecule was initially identified as a potential development form. However, because of the instability of the phase as a function of ambient relative humidity, investigations of other polymorphs of the zwitterion and basic and acidic salt screening were conducted to identify an acceptable physical form for long-term development. An HCl dihydrate, an unsolvated sulfate salt, a hexahydrate calcium salt, and a monohydrate of the zwitterion were identified as potentially viable phases. The quality attributes of these phases were then compared along with their propensity to undergo acid-promoted degradation.

  DOI：

  10.1021/op200192n
• 作为产物：
  描述：

  2,6-dichloro-3-isothiocyanatopyridine 在 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 cyanoborohydride 、 sodium carbonate 、 potassium carbonate 、 溶剂黄146 、 N,N-二异丙基乙胺 、 sodium hydroxide 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 甲醇 、 二氯甲烷 、 水 、 二甲基亚砜 、 N,N-二甲基甲酰胺 为溶剂， 生成 1-(3-fluoro-4-(5-(1-phenylcyclopropyl)thiazolo[5,4-b]pyridin-2-yl)benzyl)azetidine-3-carboxylic acid
  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
• JP2011524906A
  申请人：——

  公开号：JP2011524906A

  公开（公告）日：2011-09-08
• US7842685B2
  申请人：——

  公开号：US7842685B2

  公开（公告）日：2010-11-30