2-氯-6-甲基-3-硝基-N,N-二丙基吡啶-4-胺 | 1028309-04-7

• 分子结构分类: 有机化合物 - 有机1,3-偶极化合物 - 烯丙基型1,3-偶极有机化合物
• 中文名称: 2-氯-6-甲基-3-硝基-N,N-二丙基吡啶-4-胺
• 英文名称: 2-chloro-6-methyl-3-nitro-N,N-dipropylpyridin-4-amine
• CAS: 1028309-04-7
• 化学式: C₁₂H₁₈ClN₃O₂
• 分子量: 271.747
• InChiKey: NXCFHULUTUORMA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  18
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.58
• 拓扑面积：
  62
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-氯-6-甲基-3-硝基-N,N-二丙基吡啶-4-胺 在 sodium hydride 作用下， 以 N,N-二甲基乙酰胺 、 mineral oil 为溶剂， 反应 37.5h， 生成 ethyl N-(2-bromo-4-isopropylphenyl)-N-(4-(dipropylamino)-6-methyl-3-nitropyridin-2-yl)glycinate
  参考文献：
  名称：

  Synthesis, binding affinity, radiolabeling, and microPET evaluation of 4-(2-substituted-4-substituted)-8-(dialkylamino)-6-methyl-1-substituted-3,4-dihydropyrido[2,3-b]pyrazin-2(1H)-ones as ligands for brain corticotropin-releasing factor type-1 (CRF1) receptors

  摘要：

  Compounds 1-14 were synthesized in a search for high-affinity CRF1 receptor ligands that could be radiolabeled with C-11 or F-18 for use as positron emission tomography (PET) radiotracers. Derivatives of 2 were developed which contained amide N-fluoroalkyl substituents. Compounds [F-18]24 and [F-18]25 were found to have appropriate lipophilicities of logP(7.4) = 2.2 but microPET imaging with [F-18]25 demonstrated limited brain uptake. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2015.10.010
• 作为产物：
  描述：

  4-羟基-6-甲基-3-硝基-2-吡啶醇 在 环己胺 、 N,N-二异丙基乙胺 、 三氯氧磷 作用下， 以 甲醇 、 乙腈 为溶剂， 反应 80.67h， 生成 2-氯-6-甲基-3-硝基-N,N-二丙基吡啶-4-胺
  参考文献：
  名称：

  Synthesis, Structure−Activity Relationships, and in Vivo Properties of 3,4-Dihydro-1H-pyrido[2,3-b]pyrazin-2-ones as Corticotropin-Releasing Factor-1 Receptor Antagonists

  摘要：

  Corticotropin releasing factor (CRF) is the primary regulator of the hypothalamus-pituitary-adrenal (HPA) axis, coordinating the endocrine, behavioral, and autonomic responses to stress. It has been postulated that small molecules that can antagonize the binding of CRF, to its receptor may serve as a treatment for anxiety-related and/or affective disorders. Members within a series of 3,4-dihydro-1H-pyrido[2,3-b]pyrazin-2-ones, exemplified by compound 2 (IC50 = 0.70 nM), were found to be very potent antagonists of CRF1. Compound 8w showed high CRF1 receptor binding affinity and was examined further in vivo. The compound was efficacious in a defensive withdrawal model of anxiety in rats and had a long half-life and reasonable oral bioavailability in dog pharmacokinetic studies.

  DOI：

  10.1021/jm049737f

文献信息

• Synthesis, Structure−Activity Relationships, and in Vivo Properties of 3,4-Dihydro-1<i>H</i>-pyrido[2,3-<i>b</i>]pyrazin-2-ones as Corticotropin-Releasing Factor-1 Receptor Antagonists
  作者：Carolyn D. Dzierba、Amy G. Takvorian、Maria Rafalski、Padmaja Kasireddy-Polam、Harvey Wong、Thaddeus F. Molski、Ge Zhang、Yu-Wen Li、Snjezana Lelas、Yong Peng、John F. McElroy、Robert C. Zaczek、Rebecca A. Taub、Andrew P. Combs、Paul J. Gilligan、George L. Trainor

  DOI：10.1021/jm049737f

  日期：2004.11.1

  Corticotropin releasing factor (CRF) is the primary regulator of the hypothalamus-pituitary-adrenal (HPA) axis, coordinating the endocrine, behavioral, and autonomic responses to stress. It has been postulated that small molecules that can antagonize the binding of CRF, to its receptor may serve as a treatment for anxiety-related and/or affective disorders. Members within a series of 3,4-dihydro-1H-pyrido[2,3-b]pyrazin-2-ones, exemplified by compound 2 (IC50 = 0.70 nM), were found to be very potent antagonists of CRF1. Compound 8w showed high CRF1 receptor binding affinity and was examined further in vivo. The compound was efficacious in a defensive withdrawal model of anxiety in rats and had a long half-life and reasonable oral bioavailability in dog pharmacokinetic studies.
• Synthesis, binding affinity, radiolabeling, and microPET evaluation of 4-(2-substituted-4-substituted)-8-(dialkylamino)-6-methyl-1-substituted-3,4-dihydropyrido[2,3-b]pyrazin-2(1H)-ones as ligands for brain corticotropin-releasing factor type-1 (CRF1) receptors
  作者：Jeffrey S. Stehouwer、Chase H. Bourke、Michael J. Owens、Ronald J. Voll、Clinton D. Kilts、Mark M. Goodman

  DOI：10.1016/j.bmcl.2015.10.010

  日期：2015.11

  Compounds 1-14 were synthesized in a search for high-affinity CRF1 receptor ligands that could be radiolabeled with C-11 or F-18 for use as positron emission tomography (PET) radiotracers. Derivatives of 2 were developed which contained amide N-fluoroalkyl substituents. Compounds [F-18]24 and [F-18]25 were found to have appropriate lipophilicities of logP(7.4) = 2.2 but microPET imaging with [F-18]25 demonstrated limited brain uptake. (C) 2015 Elsevier Ltd. All rights reserved.