(8R)-8-(3,5-difluorophenyl)-6,8-dimethyl-6,9-diazaspiro[4.5]decan-10-one | 1211383-48-0

• 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)-6,8-dimethyl-6,9-diazaspiro[4.5]decan-10-one
• CAS: 1211383-48-0
• 化学式: C₁₆H₂₀F₂N₂O
• 分子量: 294.344
• InChiKey: QEEARULBGHVIKP-HNNXBMFYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  21
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  32.3
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (8R)-8-(3,5-difluorophenyl)-6,8-dimethyl-6,9-diazaspiro[4.5]decan-10-one 在 copper(l) iodide 、 四(三苯基膦)钯 、 palladium 10% on activated carbon 、 氢气 、 sodium hydride 、 三乙胺 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 121.5h， 生成 (R)-5-(3-((R)-8-(3,5-difluorophenyl)-6,8-dimethyl-10-oxo-6,9-diazaspiro[4.5]decan-9-yl)propyl)-1,3-dihydrospiro[indene-2,3'-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 、 sodium cyanoborohydride 、 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 47.5h， 生成 (8R)-8-(3,5-difluorophenyl)-6,8-dimethyl-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

• 3- AND 6-QUINOLINES WITH N-ATTACHED HETEROCYCLIC CGRP RECEPTOR ANTAGONISTS
  申请人：Wood Michael R.

  公开号：US20110306604A1

  公开（公告）日：2011-12-15

  Compounds of Formula (I): (where variables R 1A , R 1B , R 2 , R 3 , R 4 , A, and Z are as defined herein) which are useful as antagonists of CGRP receptors, and useful in the treatment or prevention of diseases in which CGRP receptors are involved, such as headache, and in particular migraine and cluster headache. 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 receptors are involved.

  公式(I)的化合物：（其中变量R1A，R1B，R2，R3，R4，A和Z的定义如本文所述），可用作CGRP受体的拮抗剂，对于治疗或预防CGRP受体参与的疾病，如头痛，尤其是偏头痛和集群头痛非常有用。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受体参与的上述疾病方面使用这些化合物和组合物。
• US8507477B2
  申请人：——

  公开号：US8507477B2

  公开（公告）日：2013-08-13
• [¹¹C]MK-4232: The First Positron Emission Tomography Tracer for the Calcitonin Gene-Related Peptide Receptor
  作者：Ian M. Bell、Steven N. Gallicchio、Craig A. Stump、Joseph G. Bruno、Hong Fan、Liza T. Gantert、Eric D. Hostetler、Amanda L. Kemmerer、Melody McWherter、Eric L. Moore、Scott D. Mosser、Mona L. Purcell、Kerry Riffel、Christopher A. Salvatore、Sandra Sanabria-Bohórquez、Donnette D. Staas、Rebecca B. White、Mangay Williams、C. Blair Zartman、Jacquelynn J. Cook、Richard J. Hargreaves、Stefanie A. Kane、Samuel L. Graham、Harold G. Selnick

  DOI：10.1021/ml400199p

  日期：2013.9.12

  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.