tert-butyl 4-(2-(7-(2-methoxyethoxy)imidazo[1,2-a]pyridin-3-yl)quinolin-8-yloxy)piperidine-1-carboxylate | 1070896-55-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: tert-butyl 4-(2-(7-(2-methoxyethoxy)imidazo[1,2-a]pyridin-3-yl)quinolin-8-yloxy)piperidine-1-carboxylate
• 英文别名: tert-butyl 4-[2-[7-(2-methoxyethoxy)imidazo[1,2-a]pyridin-3-yl]quinolin-8-yl]oxypiperidine-1-carboxylate
• CAS: 1070896-55-7
• 化学式: C₂₉H₃₄N₄O₅
• 分子量: 518.613
• InChiKey: RKQWDKPRDFHCBK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5
• 重原子数：
  38
• 可旋转键数：
  9
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  87.4
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  tert-butyl 4-(2-(7-(2-methoxyethoxy)imidazo[1,2-a]pyridin-3-yl)quinolin-8-yloxy)piperidine-1-carboxylate 在 三氟乙酸 、 碳酸氢钠 作用下， 以 二氯甲烷 、 水 为溶剂， 生成 2-(7-(2-methoxyethoxy)imidazo[1,2-a]pyridin-3-yl)-8-(piperidin-4-yloxy)quinoline
  参考文献：
  名称：

  WO2008/124323

  摘要：

  公开号：
• 作为产物：
  描述：

  8-苄氧基-2-氧代-1H-喹啉 在 四(三苯基膦)钯 、 草酰氯 、 10% palladium hydroxide on charcoal 、 甲酸铵 、 palladium diacetate 、 potassium carbonate 、 caesium carbonate 、 N,N-二甲基甲酰胺 作用下， 以 1,4-二氧六环 、 乙醇 、 N,N-二甲基乙酰胺 、 水 、 1,2-二氯乙烷 为溶剂， 反应 62.0h， 生成 tert-butyl 4-(2-(7-(2-methoxyethoxy)imidazo[1,2-a]pyridin-3-yl)quinolin-8-yloxy)piperidine-1-carboxylate
  参考文献：
  名称：

  Discovery of a Novel Class of Imidazo[1,2-a]Pyridines with Potent PDGFR Activity and Oral Bioavailability

  摘要：

  The in silico construction of a PDGFR beta kinase homology model and ensuing medicinal chemistry guided by molecular modeling, led to the identification of potent, small molecule inhibitors of PDGFR Subsequent exploration of structure-activity relationships (SAR) led to the incorporation of a constrained secondary amine to enhance selectivity. Further refinements led to the integration of a fluorine substituted piperidine, which resulted M significant reduction of P-glycoprotein (Pgp) mediated efflux and improved bioavailability. Compound 28 displayed oral exposure in rodents and had a pronounced effect in a pharmacokinetic-pharmacodynamic (PKPD) assay.

  DOI：

  10.1021/ml4003953

文献信息

• IMIDAZO[1,2-A]PYRIDINE COMPOUNDS AS RECEPTOR TYROSINE KINASE INHIBITORS
  申请人：Allen Shelley

  公开号：US20100029633A1

  公开（公告）日：2010-02-04

  Compounds of Formula I: in which A, B, R 1 , R 1a , R 2 , R 3 , R 4 , R 5 R 6 , R 7 and R 8 have the meanings given in the specification, are receptor tyrosine inhibitors useful in the treatment of diseases mediated by class 3 and class 5 receptor tyrosine kinases. Particular compounds of this invention have also been found to be inhibitors of Pim- 1 .

  式I的化合物：其中A、B、R1、R1a、R2、R3、R4、R5R6、R7和R8具有规范中给出的含义，是在治疗由类3和类5受体酪氨酸激酶介导的疾病中有用的受体酪氨酸激酶抑制剂。本发明的特定化合物也被发现是Pim-1的抑制剂。
• Imidazo[1,2-a]pyridine compounds as receptor tyrosine kinase inhibitors
  申请人：Array BioPharma Inc.

  公开号：US08138181B2

  公开（公告）日：2012-03-20

  Compounds of Formula I: in which A, B, R1, R1a, R2, R3, R4, R5 R6, R7 and R8 have the meanings given in the specification, are receptor tyrosine inhibitors useful in the treatment of diseases mediated by class 3 and class 5 receptor tyrosine kinases. Particular compounds of this invention have also been found to be inhibitors of Pim-1.

  公式I的化合物：其中A、B、R1、R1a、R2、R3、R4、R5、R6、R7和R8的含义如规范中所述，是可用于治疗受类3和类5受体酪氨酸激酶介导的疾病的受体酪氨酸激酶抑制剂。本发明的特定化合物也被发现是Pim-1的抑制剂。
• US8138181B2
  申请人：——

  公开号：US8138181B2

  公开（公告）日：2012-03-20
• [EN] IMIDAZO[1,2-A]PYRIDINE COMPOUNDS AS RECEPTOR TYROSINE KINASE INHIBITORS<br/>[FR] COMPOSÉS IMIDAZO[1,2-A]PYRIDINE UTILISÉS COMME INHIBITEURS DES RÉCEPTEURS À ACTIVITÉ TYROSINE KINASE
  申请人：ARRAY BIOPHARMA INC

  公开号：WO2008124323A1

  公开（公告）日：2008-10-16

  [EN] Compounds of Formula I: in which A, B, R¹, R^1a, R², R³, R⁴, R⁵ R⁶, R⁷ and R⁸ have the meanings given in the specification, are receptor tyrosine inhibitors useful in the treatment of diseases mediated by class 3 and class 5 receptor tyrosine kinases. Particular compounds of this invention have also been found to be inhibitors of Pim-1.
  [FR] Cette invention a trait à des composés de formule I dans laquelle A, B, R1, R1a, R2, R3, R4, R5 R6, R7 et R8 ont la signification énoncée dans la description, lesdits composés étant des inhibiteurs des récepteurs à activité tyrosine kinase utilisés dans le traitement des maladies associées aux récepteurs à activité tyrosine kinase de classe 3 et de classe 5. Des composés particuliers de l'invention se sont également avérés inhibiteurs de Pim-1.
• Discovery of a Novel Class of Imidazo[1,2-<i>a</i>]Pyridines with Potent PDGFR Activity and Oral Bioavailability
  作者：Erik J. Hicken、Fred P. Marmsater、Mark C. Munson、Stephen T. Schlachter、John E. Robinson、Shelley Allen、Laurence E. Burgess、Robert Kirk DeLisle、James P. Rizzi、George T. Topalov、Qian Zhao、Julie M. Hicks、Nicholas C. Kallan、Eugene Tarlton、Andrew Allen、Michele Callejo、April Cox、Sumeet Rana、Nathalie Klopfenstein、Richard Woessner、Joseph P. Lyssikatos

  DOI：10.1021/ml4003953

  日期：2014.1.9

  The in silico construction of a PDGFR beta kinase homology model and ensuing medicinal chemistry guided by molecular modeling, led to the identification of potent, small molecule inhibitors of PDGFR Subsequent exploration of structure-activity relationships (SAR) led to the incorporation of a constrained secondary amine to enhance selectivity. Further refinements led to the integration of a fluorine substituted piperidine, which resulted M significant reduction of P-glycoprotein (Pgp) mediated efflux and improved bioavailability. Compound 28 displayed oral exposure in rodents and had a pronounced effect in a pharmacokinetic-pharmacodynamic (PKPD) assay.