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3-(1,5-dimethyl-1H-pyrazol-4-yl)-1-methyl-6-(pyridin-2-ylmethoxy)-1H-pyrazolo[3,4-b]pyrazine | 1539296-50-8

中文名称
——
中文别名
——
英文名称
3-(1,5-dimethyl-1H-pyrazol-4-yl)-1-methyl-6-(pyridin-2-ylmethoxy)-1H-pyrazolo[3,4-b]pyrazine
英文别名
3-(1,5-Dimethylpyrazol-4-yl)-1-methyl-6-(pyridin-2-ylmethoxy)pyrazolo[3,4-b]pyrazine;3-(1,5-dimethylpyrazol-4-yl)-1-methyl-6-(pyridin-2-ylmethoxy)pyrazolo[3,4-b]pyrazine
3-(1,5-dimethyl-1H-pyrazol-4-yl)-1-methyl-6-(pyridin-2-ylmethoxy)-1H-pyrazolo[3,4-b]pyrazine化学式
CAS
1539296-50-8
化学式
C17H17N7O
mdl
——
分子量
335.368
InChiKey
MXYXLYAPGNYCAH-UHFFFAOYSA-N
BEILSTEIN
——
EINECS
——
  • 物化性质
  • 计算性质
  • ADMET
  • 安全信息
  • SDS
  • 制备方法与用途
  • 上下游信息
  • 反应信息
  • 文献信息
  • 表征谱图
  • 同类化合物
  • 相关功能分类
  • 相关结构分类

计算性质

  • 辛醇/水分配系数(LogP):
    1
  • 重原子数:
    25
  • 可旋转键数:
    4
  • 环数:
    4.0
  • sp3杂化的碳原子比例:
    0.24
  • 拓扑面积:
    83.5
  • 氢给体数:
    0
  • 氢受体数:
    6

反应信息

  • 作为产物:
    描述:
    6-chloro-3-iodo-1-methyl-1H-pyrazolo[3,4-b]pyrazine 在 potassium tert-butylate异丙基氯化镁lithium chloride 作用下, 以 四氢呋喃 为溶剂, 反应 2.33h, 生成 3-(1,5-dimethyl-1H-pyrazol-4-yl)-1-methyl-6-(pyridin-2-ylmethoxy)-1H-pyrazolo[3,4-b]pyrazine
    参考文献:
    名称:
    1-甲基-3-(4-甲基吡啶-3-基)-6-(吡啶-2-基甲氧基)-1 H-吡唑并-[3,4- b ]吡嗪(PF470)的发现和临床前表征高效,选择性和有效的代谢型谷氨酸受体5(mGluR5)负变构调节剂
    摘要:
    本文公开了一系列新颖的吡唑并吡嗪类作为mGluR5负变构调节剂(NAM)。从高通量筛选(HTS)命中(1)开始,进行了系统的结构-活性关系(SAR)研究,重点关注平衡药理学效力与理化和药代动力学(PK)特性。这种努力导致的发现1-甲基-3-(4-甲基吡啶-3-基)-6-(吡啶-2-基甲氧基)-1 ħ -吡唑并[3,4- b ]吡嗪(PF470,14)作为高效,选择性和口服可生物利用的mGluR5 NAM。化合物14表现出在1-甲基-4-苯基-1,2,3,6-四氢吡啶(MPTP)渲染的帕金森非人灵长类动物的模型稳健功效升-DOPA引起的运动障碍(PD-LID)。然而,由于一项为期90天的NHP监管毒理学研究中潜在的机制介导的发现与延迟型免疫介导的IV型超敏反应相一致,因此终止了14种药物的临床开发。
    DOI:
    10.1021/jm401622k
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文献信息

  • Discovery and Preclinical Characterization of 1-Methyl-3-(4-methylpyridin-3-yl)-6-(pyridin-2-ylmethoxy)-1<i>H</i>-pyrazolo-[3,4-<i>b</i>]pyrazine (PF470): A Highly Potent, Selective, and Efficacious Metabotropic Glutamate Receptor 5 (mGluR5) Negative Allosteric Modulator
    作者:Lei Zhang、Gayatri Balan、Gabriela Barreiro、Brian P. Boscoe、Lois K. Chenard、Julie Cianfrogna、Michelle M. Claffey、Laigao Chen、Karen J. Coffman、Susan E. Drozda、Joshua R. Dunetz、Kari R. Fonseca、Paul Galatsis、Sarah Grimwood、John T. Lazzaro、Jessica Y. Mancuso、Emily L. Miller、Matthew R. Reese、Bruce N. Rogers、Isao Sakurada、Marc Skaddan、Deborah L. Smith、Antonia F. Stepan、Patrick Trapa、Jamison B. Tuttle、Patrick R. Verhoest、Daniel P. Walker、Ann S. Wright、Margaret M. Zaleska、Kenneth Zasadny、Christopher L. Shaffer
    DOI:10.1021/jm401622k
    日期:2014.2.13
    A novel series of pyrazolopyrazines is herein disclosed as mGluR5 negative allosteric modulators (NAMs). Starting from a high-throughput screen (HTS) hit (1), a systematic structure–activity relationship (SAR) study was conducted with a specific focus on balancing pharmacological potency with physicochemical and pharmacokinetic (PK) properties. This effort led to the discovery of 1-methyl-3-(4-met
    本文公开了一系列新颖的吡唑并吡嗪类作为mGluR5负变构调节剂(NAM)。从高通量筛选(HTS)命中(1)开始,进行了系统的结构-活性关系(SAR)研究,重点关注平衡药理学效力与理化和药代动力学(PK)特性。这种努力导致的发现1-甲基-3-(4-甲基吡啶-3-基)-6-(吡啶-2-基甲氧基)-1 ħ -吡唑并[3,4- b ]吡嗪(PF470,14)作为高效,选择性和口服可生物利用的mGluR5 NAM。化合物14表现出在1-甲基-4-苯基-1,2,3,6-四氢吡啶(MPTP)渲染的帕金森非人灵长类动物的模型稳健功效升-DOPA引起的运动障碍(PD-LID)。然而,由于一项为期90天的NHP监管毒理学研究中潜在的机制介导的发现与延迟型免疫介导的IV型超敏反应相一致,因此终止了14种药物的临床开发。
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同类化合物

S-(1-乙烯基-1H-吡唑并[3,4-b]吡嗪-5-基)乙硫酸酯 6-甲基-1H-吡唑并[3,4-b]吡嗪-3-醇 6-氯-1H-吡唑并[3,4-B]吡嗪 6-氨基-1,3-二甲基-1H-吡唑并[3,4-b]吡嗪-5-甲腈 5-甲基-1H-吡唑并[3,4-b]吡嗪-3-醇 5-溴-3-甲基-1H-吡唑并[3,4-b]吡嗪 5-溴-1H-吡唑并[3,4-b]吡嗪-3-胺 4,7-二氮杂-1H-吲唑 3-甲基-1H-吡唑并[3,4-b]吡嗪 3-溴-1H-吡唑并[3,4-B]吡嗪 3,6-二氨基-1H-吡唑并[3,4-b]吡嗪-5-甲腈 2-(1H-吡唑并[3,4-b]吡嗪-5-基氨基)乙醇 2,3,6,7-四氢-3,6-二氧代-1H-吡唑并[3,4-b]吡嗪-5-甲腈 1H-吡唑并[3,4-B]吡嗪-3-氨基 1-甲基吡唑并[3,4-b]吡嗪-3-胺 1-甲基-1,2-二氢-3H-吡唑并[3,4-b]吡嗪-3-酮 1-(6-羟基-1,3-二甲基-1H-吡唑并[3,4-b]吡嗪-5-基)-乙酮 1-(1,3,6-三甲基-1H-吡唑并[3,4-b]吡嗪-5-基)-乙酮 1,5,6-三甲基-1H-吡唑并[3,4-b]吡嗪 1,5,6-三甲基-1,2-二氢-3H-吡唑并[3,4-b]吡嗪-3-酮 1,3-dimethyl-6-phenylpyrazolo<3,4-b>pyrazine 4-oxide ethyl 6-methoxy-1-((6-methoxy-5-methylpyrimidin-4-yl)methyl)-1H-pyrazolo[3,4-b]pyrazine-3-carboxylate ethyl 6-chloro-1-((6-methoxy-5-methylpyrimidin-4-yl)methyl)-1H-pyrazolo[3,4-b]pyrazine-3-carboxylate 1-(1-ethyl-propyl)-5-(2-methoxy-4-trifluoromethoxy-phenyl)-6-methyl-1H-pyrazolo[3,4-b]pyrazine 1-(1-Ethyl-propyl)-5-(2-methoxy-4-trifluoromethoxy-phenyl)-3,6-dimethyl-1H-pyrazolo[3,4-b]pyrazine 1,7-diacetonyl-3,5-dinitrodipyrazolo<3,4-b;4',3'-e>pyrazine trifluoro-methanesulfonic acid 3-[6-ethyl-1-(2-methoxy-1-methyl-ethyl)-3-methyl-1H-pyrazolo[3,4-b]pyrazin-5-yl]-6-isopropyl-pyridin-2-yl ester 6-ethyl-5-(2-ethyl-6-isopropyl-pyridin-3-yl)-1-(2-methoxy-1-methyl-ethyl)-3-methyl-1H-pyrazolo[3,4-b]pyrazine 6-(4-methoxyphenyl)-1,3-dimethylpyrazolo<3,4-b>pyrazin-5(4H)-one 3-{[(2S)-2-amino-3-(3-thienyl)propyl]oxy}-6-(2-methyl-3-furanyl)-5-(3-methyl-1H-pyrazolo[3,4-b]pyrazin-5-yl)-2-pyridinamine 3-(3-(difluoromethoxy)pyridin-2-yl)-1-methyl-6-(pyridin-2-ylmethoxy)-1H-pyrazolo[3,4-b]pyrazine 1-methyl-6-(pyridin-2-ylmethoxy)-3-(4-methyl-pyridazin-3-yl)-1H-pyrazolo[3,4-b]pyrazine 1-methyl-3-(3-methylpyridin-2-yl)-6-(pyridin-2-ylmethoxy)-1H-pyrazolo[3,4-b]pyrazine 6-isopropyl-1,3-dimethyl-1H-pyrazolo[3,4-b]pyrazin-5(4H)-one 1,3,6-trimethyl-1H-pyrazolo[3,4-b]pyrazin-5(4H)-one 1-benzyl-1,2-dihydro-pyrazolo[3,4-b]pyrazin-3-one 5,6-diphenyl-1,2-dihydro-pyrazolo[3,4-b]pyrazin-3-one 6-benzyl-1,3-dimethyl-1H-pyrazolo[3,4-b]pyrazin-5(4H)- 1H,7H-dipyrazolo<3,4-b;4',3'-e>pyrazine 4H-Pyrazolo[3,4-b]pyrazin-4-ol 5,6-dimethyl-1,2-dihydro-pyrazolo[3,4-b]pyrazin-3-one 3-(6-chloropyridin-2-yl)-1H-pyrazolo[3,4-b]pyrazine 2-(1H-Pyrazolo[3,4-b]pyrazin-1-yl)ethanol 1,1-dimethylethyl [(1S)-2-{[2-amino-6-(2-methyl-3-furanyl)-5-(3-methyl-1H-pyrazolo[3,4-b]pyrazin-5-yl)-3-pyridinyl]oxy}-1-(3-thienylmethyl)ethyl]carbamate [(S)-1-(2-Methyl-propane-1-sulfonyl)-piperidin-3-yl]-[3-(1H-pyrazolo[3,4-b]pyrazin-5-yl)-pyridin-2-yl]-amine N-[(3S)-1-(2-methylpropylsulfonyl)piperidin-3-yl]-3-[1-(2-trimethylsilylethoxymethyl)pyrazolo[3,4-b]pyrazin-5-yl]pyridin-2-amine 1,3-dimethyl-5-oxo-4,5-dihydro-1H-dipyrazolo[1,5-a;4',3'-e]pyrazine-6-carboxylic acid 3-(1,5-dimethyl-1H-pyrazol-4-yl)-1-methyl-6-(pyridin-2-ylmethoxy)-1H-pyrazolo[3,4-b]pyrazine 6-(4-chlorophenyl)-1,3-dimethylpyrazolo<3,4-b>pyrazine 4-oxide 5-acetoxy-6-(4-chlorophenyl)-1,3-dimethylpyrazolo<3,4-b>pyrazine