(8R)-8-(3,5-difluorophenyl)-8-methyl-6,9-diazaspiro[4.5]decan-10-one | 1189569-73-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: (8R)-8-(3,5-difluorophenyl)-8-methyl-6,9-diazaspiro[4.5]decan-10-one
• CAS: 1189569-73-0
• 化学式: C₁₅H₁₈F₂N₂O
• 分子量: 280.318
• InChiKey: DIHHJLLPRVUNLK-AWEZNQCLSA-N

物化性质

• 沸点：
  454.6±45.0 °C(Predicted)
• 密度：
  1.25±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  20
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  41.1
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (8R)-8-(3,5-difluorophenyl)-8-methyl-6,9-diazaspiro[4.5]decan-10-one 在 二(三叔丁基膦)钯 、 N-甲基二环己基胺 、 sodium hydride 作用下， 以 N,N-二甲基乙酰胺 、 N,N-二甲基甲酰胺 为溶剂， 反应 19.83h， 生成 (S)-3-((E)-3-((R)-8-(3,5-difluorophenyl)-8-methyl-10-oxo-6,9-diazaspiro[4.5]decan-9-yl)prop-1-en-1-yl)-5,7-dihydrospiro[cyclopenta[b]pyridine-6,3'-pyrrolo[2,3-b]pyridin]-2'(1'H)-one
  参考文献：
  名称：

  [¹¹C]MK-4232: The First Positron Emission Tomography Tracer for the Calcitonin Gene-Related Peptide Receptor

  摘要：

  Rational modification of the potent calcitonin gene-related peptide (CGRP) receptor antagonist MK-3207 led to a series of analogues with enhanced CNS penetrance and a convenient chemical handle for introduction of a radiolabel. A number of C-11-tracers were synthesized and evaluated in vivo, leading to the identification of [C-11](8) ([C-11]MK-4232), the first positron emission tomography tracer for the CGRP receptor.

  DOI：

  10.1021/ml400199p
• 作为产物：
  描述：

  tert-butyl [1-(3,5-difluorophenyl)-1-methyl-2-oxoethyl]carbamate 在 盐酸 、 溶剂黄146 作用下， 以 甲醇 、 5,5-dimethyl-1,3-cyclohexadiene 、 乙酸乙酯 为溶剂， 反应 4.5h， 生成 (8R)-8-(3,5-difluorophenyl)-8-methyl-6,9-diazaspiro[4.5]decan-10-one 、 (8S)-8-(3,5-difluorophenyl)-8-methyl-6,9-diazaspiro[4.5]decan-10-one
  参考文献：
  名称：

  [¹¹C]MK-4232: The First Positron Emission Tomography Tracer for the Calcitonin Gene-Related Peptide Receptor

  摘要：

  Rational modification of the potent calcitonin gene-related peptide (CGRP) receptor antagonist MK-3207 led to a series of analogues with enhanced CNS penetrance and a convenient chemical handle for introduction of a radiolabel. A number of C-11-tracers were synthesized and evaluated in vivo, leading to the identification of [C-11](8) ([C-11]MK-4232), the first positron emission tomography tracer for the CGRP receptor.

  DOI：

  10.1021/ml400199p

文献信息

• RADIOLABELED CGRP ANTAGONISTS
  申请人：Bell Ian M.

  公开号：US20120121508A1

  公开（公告）日：2012-05-17

  The present invention is directed to radiolabeled CGRP receptor antagonists which are useful for the quantitative imaging of CGRP receptors in mammals.

  本发明涉及用于哺乳动物中CGRP受体定量成像的放射性标记的CGRP受体拮抗剂。
• Monocyclic CGRP receptor antagonists
  申请人：Selnick Harold G.

  公开号：US08765759B2

  公开（公告）日：2014-07-01

  The present invention is directed to compounds of the formula: (wherein variables A1, A2, A3, G1, G2, G3, G4, J, Ea, Eb, Ec, R6, R7, and Y are as described herein) which are antagonists of CGRP receptors and which are useful in the treatment or prevention of diseases in which CGRP is involved, such as migraine. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which CGRP is involved.

  本发明涉及以下式子的化合物:(其中变量A1、A2、A3、G1、G2、G3、G4、J、Ea、Eb、Ec、R6、R7和Y如本文所述)，这些化合物是CGRP受体的拮抗剂，可用于治疗或预防CGRP参与的疾病，如偏头痛。本发明还涉及包含这些化合物的制药组合物以及这些化合物和组合物在预防或治疗CGRP参与的疾病中的使用。
• MONOCYCLIC CGRP RECEPTOR ANTAGONISTS
  申请人：Selnick Harold G.

  公开号：US20110021516A1

  公开（公告）日：2011-01-27

  The present invention is directed to compounds of the formula (I): (wherein variables A 1 , A 2 , A 3 , A 4 , A 5 , A 6 , A 7 , A 8 , G 1 , G 2 , G 3 , G 4 , J, Q, E a , E b , E c , R 6 , R 7 , R PG and Y are as described herein) which are antagonists of CGRP receptors and which are useful in the treatment or prevention of diseases in which CGRP is involved, such as migraine. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which CGRP is involved.

  本发明涉及式(I)的化合物：（其中变量A1、A2、A3、A4、A5、A6、A7、A8、G1、G2、G3、G4、J、Q、Ea、Eb、Ec、R6、R7、RPG和Y如本文所述），它们是CGRP受体拮抗剂，并且在治疗或预防CGRP参与的疾病，如偏头痛中有用。本发明还涉及包含这些化合物的制药组合物以及在预防或治疗CGRP参与的这些疾病中使用这些化合物和组合物。
• [EN] MONOCYCLIC CGRP RECEPTOR ANTAGONISTS<br/>[FR] ANTAGONISTES DES RÉCEPTEURS CGRP MONOCYCLIQUES
  申请人：MERCK & CO INC

  公开号：WO2009120652A3

  公开（公告）日：2009-12-30
• US8765759B2
  申请人：——

  公开号：US8765759B2

  公开（公告）日：2014-07-01