4-[[4,5-Dimethyl-6-(2-methylphenoxy)-3-oxo-pyrazin-2-yl]amino]benzonitrile

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 4-[[4,5-Dimethyl-6-(2-methylphenoxy)-3-oxo-pyrazin-2-yl]amino]benzonitrile
• 英文别名: 4-[[4,5-dimethyl-6-(2-methylphenoxy)-3-oxopyrazin-2-yl]amino]benzonitrile
• 化学式: C₂₀H₁₈N₄O₂
• 分子量: 346.389
• InChiKey: JGZCQEQHWWHKSB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  26
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  77.7
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  3,5-dibromo-1,6-dimethylpyrazin-2(1H)-one 在 D(+)-10-樟脑磺酸 、 caesium carbonate 、 乙酸乙酯 、 copper(l) chloride 作用下， 以 异丙醇 、 甲苯 为溶剂， 反应 48.0h， 生成 4-[[4,5-Dimethyl-6-(2-methylphenoxy)-3-oxo-pyrazin-2-yl]amino]benzonitrile
  参考文献：
  名称：

  Design, Synthesis, and SAR of a Novel Pyrazinone Series with Non-Nucleoside HIV-1 Reverse Transcriptase Inhibitory Activity

  摘要：

  A series of novel pyrazinones designed as non-nucleoside reverse transcriptase inhibitors (NNRTIs) was synthesized and their anti-HIV structure-activity relationship (SAR) was studied.

  DOI：

  10.1021/jm040829e

文献信息

• Hiv inhibiting pyrazinone derivatives
  申请人：——

  公开号：US20040102456A1

  公开（公告）日：2004-05-27

  This invention concerns a compound of formula 1 a N-oxide, a pharmaceutically acceptable addition salt, a quaternary amine and a stereochemically isomeric form thereof, wherein R 1 is hydrogen, hydroxy, cyano, amino, mono-or di(C 1-4 alkyl)amino, formyl, carboxyl, C 1-6 alkyl, hydroxyC 1-6 alkyl, polyhaloC 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-7 cycloalkyl, C 1-6 alkyloxy, C 1-6 alkylcarbonyl, aminocarbonyl, S(═O) m —NH 2 , mono-or di(C 1-4 alkyl)aminocarbonyl, C 1-6 alkyloxycarbonyl, C 1-6 alkylcarbonyloxy, aryl, arylC 1-6 alkyl or aryloxy; R 2 is hydrogen; halo; mercapto; formyl; cyano; carboxy; azido; hydroxy; oxiranyl; amino; mono- or di(C 1-4 alkyl)amino; formylamino; R 5 R 6 N—C(═O)—; R 7 —N═C(R 8 )—; C 1-6 alkyl-S(═O)m; aryl-S(═O) m ; optionally substituted C 2-6 alkenyl; optionally substituted C 2-6 alkynyl; C 1-6 alkyloxy; hydroxyC 1-6 alkyloxy; aminoC 1-6 alkyloxy; mono- or di(C 1-4 alkyl)amino-C 1-6 alkyloxy; C 1-6 alkylcarbonyl; arylcarbonyl; Het 1 carbonyl; C 1-6 alkyloxycarbonyl; C 1-6 alkylcarbonyloxy; aryl; aryloxy; arylC 1-6 alkyloxy; arylthio; arylC 1-6 alkylthio; mono- or di(aryl)amino; Het 1 ; Het 1 oxy; Het 1 thio; Het 1 C 1-6 alkyloxy; Het 1 C 1-6 alkylthio; mono- or di(Het 1 )amino; C 3-7 cycloalkyl; C 3-7 cycloalkyloxy; C 3-7 cycloalkylthio; C 1-6 alkylthio; hydroxyC 1-6 alkylthio; aminoC 1-6 alkylthio; mono- or di(C 1-4 alkyl)aminoC 1-6 alkylthio; optionally substituted C 1-6 alkyl; R 3 or R 4 each independently represent optionally be substituted phenyl, pyridyl, pyrimidinyl, pyrazinyl or pyridazinyl; —X— is a bivalent radical selected from —NR 14 —, —NH—NH—, —N═N—, —O—, —C 1-6 alkanediyl-, —C(═O)—, —CHOH—, —S—, —S(═O) m -; aryl is optionally substituted phenyl; Het 1 , Het 2 or Het 3 represent an optionally substituted monocyclic or bicyclic heterocycle; their use as a medicine, their processes for preparation and pharmaceutical compositions comprising them.

  本发明涉及一种式1a的化合物N-氧化物，其为药学上可接受的加合物盐，季铵盐及其立体化异构形式，其中R1为氢、羟基、氰基、氨基、单或二(C1-4烷基)氨基、甲酰基、羧基、C1-6烷基、羟基C1-6烷基、多卤C1-6烷基、C2-6烯基、C2-6炔基、C3-7环烷基、C1-6烷氧基、C1-6烷基羰基、氨基羰基、S(═O)m—NH2、单或二(C1-4烷基)氨基羰基、C1-6烷氧羰基、C1-6烷基羰氧基、芳基、芳基C1-6烷基或芳氧基；R2为氢、卤素、巯基、甲酰基、氰基、羧基、偶氮基、羟基、环氧基、氨基、单或二(C1-4烷基)氨基、甲酰氨基、R5R6N—C(═O)—、R7—N═C(R8)—、C1-6烷基-S(═O)m、芳基-S(═O)m、可选择取代的C2-6烯基、可选择取代的C2-6炔基、C1-6烷氧基、羟基C1-6烷氧基、氨基C1-6烷氧基、单或二(C1-4烷基)氨基-C1-6烷氧基、C1-6烷基羰基、芳基羰基、Het1羰基、C1-6烷氧羰基、C1-6烷基羰氧基、芳基、芳氧基、芳基C1-6烷氧基、芳硫基、芳基C1-6烷硫基、单或二(芳基)氨基、Het1、Het1氧基、Het1硫基、Het1C1-6烷氧基、Het1C1-6烷硫基、单或二(Het1)氨基、C3-7环烷基、C3-7环烷氧基、C3-7环烷硫基、C1-6烷硫基、羟基C1-6烷硫基、氨基C1-6烷硫基、单或二(C1-4烷基)氨基C1-6烷硫基、可选择取代的C1-6烷基；R3或R4各自独立地表示可选择取代的苯基、吡啶基、嘧啶基、吡嗪基或吡啶嗪基；—X—为从—NR14—、—NH—NH—、—N═N—、—O—、—C1-6烷基二元基、—C(═O)—、—CHOH—、—S—、—S(═O)m-中选择的二价基团；芳基为可选择取代的苯基；Het1、Het2或Het3表示可选择取代的单环或双环杂环；本发明还涉及其作为药物的使用、其制备方法以及包含它们的制药组合物。
• HIV INHIBITING PYRAZINONE DERIVATIVES
  申请人：JANSSEN PHARMACEUTICA N.V.

  公开号：EP1370265A1

  公开（公告）日：2003-12-17
• US7105522B2
  申请人：——

  公开号：US7105522B2

  公开（公告）日：2006-09-12
• [EN] HIV INHIBITING PYRAZINONE DERIVATIVES<br/>[FR] DERIVES DE PYRAZINONE DESTINES A INHIBER LE VIH
  申请人：JANSSEN PHARMACEUTICA NV

  公开号：WO2002078708A1

  公开（公告）日：2002-10-10

  This invention concerns compounds of formula (I) a N-oxide, a pharmaceutically acceptable addition salt, a quaternary amine and a stereochemically isomeric form thereof, wherein R1-4 and X are as defined in the claims; their use as a medicine for inhibiting HIV replication, their processes for preparation and pharmaceutical compositions comprising them.
• Design, Synthesis, and SAR of a Novel Pyrazinone Series with Non-Nucleoside HIV-1 Reverse Transcriptase Inhibitory Activity
  作者：Jan Heeres、Marc R. de Jonge、Lucien M. H. Koymans、Frits F. D. Daeyaert、Maarten Vinkers、Koen J. A. Van Aken、Eddy Arnold、Kalyan Das、Amuri Kilonda、Georges J. Hoornaert、Frans Compernolle、Marek Cegla、Rasha A. Azzam、Koen Andries、Marie-Pierre de Béthune、Hilde Azijn、Rudi Pauwels、Paul J. Lewi、Paul A. J. Janssen

  DOI：10.1021/jm040829e

  日期：2005.3.1

  A series of novel pyrazinones designed as non-nucleoside reverse transcriptase inhibitors (NNRTIs) was synthesized and their anti-HIV structure-activity relationship (SAR) was studied.