3,5-dichloro-6-(2,6-difluoro-4-methoxyphenyl)-1-((2S)-2-methylbutyl)-2(1H)-pyrazinone

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 3,5-dichloro-6-(2,6-difluoro-4-methoxyphenyl)-1-((2S)-2-methylbutyl)-2(1H)-pyrazinone
• 英文别名: 3,5-dichloro-6-(2,6-difluoro-4-methoxyphenyl)-1-[(2S)-2-methylbutyl]-2(1H)-pyrazinone；3,5-dichloro-6-(2,6-difluoro-4-methoxyphenyl)-1-[2(S)-methylbutyl]-2(1H)-pyrazinone；3,5-dichloro-6-(2,6-difluoro-4-methoxyphenyl)-1-[(2S)-2-methylbutyl]pyrazin-2-one
• 化学式: C₁₆H₁₆Cl₂F₂N₂O₂
• 分子量: 377.218
• InChiKey: MJVFVFAQEUZRNQ-QMMMGPOBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  24
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  41.9
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  3,5-dichloro-6-(2,6-difluoro-4-methoxyphenyl)-1-((2S)-2-methylbutyl)-2(1H)-pyrazinone 在 三溴化硼 、 四丁基碘化铵 、 potassium carbonate 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 2.25h， 生成 phenylmethyl N-[3-[4-[3-chloro-1,6-dihydro-1-[(2S)-2-methylbutyl]-6-oxo-5-(1H-pyrazol-1-yl)-2-pyrazinyl]-3,5-difluorophenoxy]propyl]-N-methylcarbamate
  参考文献：
  名称：

  Tubulin modulating antifungal and antiproliferative pyrazinone derivatives

  摘要：

  A novel class of synthetic tubulin polymerization disruptors, based on a substituted pyrazin-2-one core, has been discovered. These molecules have proven to be potent broad spectrum fungicides, with activity on agriculturally important ascomycete and basidiomycete pathogens. They have also been found to be particularly potent against human rhabdomyosarcoma cells. Using an efficient synthetic route, the agricultural and medicinal activity was explored. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2015.08.038
• 作为产物：
  描述：

  2,6-二氟-4-甲氧基苯甲醛 在 sodium hydrogensulfite 作用下， 以 甲醇 、 水 、 氯苯 为溶剂， 反应 4.83h， 生成 3,5-dichloro-6-(2,6-difluoro-4-methoxyphenyl)-1-((2S)-2-methylbutyl)-2(1H)-pyrazinone
  参考文献：
  名称：

  Tubulin modulating antifungal and antiproliferative pyrazinone derivatives

  摘要：

  A novel class of synthetic tubulin polymerization disruptors, based on a substituted pyrazin-2-one core, has been discovered. These molecules have proven to be potent broad spectrum fungicides, with activity on agriculturally important ascomycete and basidiomycete pathogens. They have also been found to be particularly potent against human rhabdomyosarcoma cells. Using an efficient synthetic route, the agricultural and medicinal activity was explored. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2015.08.038

文献信息

• Pyrazinones As Cellular Proliferation Inhibitors
  申请人：Bereznak James Francis

  公开号：US20090186907A1

  公开（公告）日：2009-07-23

  This invention pertains to a method of inhibiting undesired animal cellular proliferation said method comprising contacting an animal cell with a compound of Formula 1 and all pharmaceutically acceptable, salts, N-oxides, hydrates, solvates, or geometric and stereoisomers thereof: wherein R 1 is NR 4 R 5 , N═CR 19 R 21 , OR 6 , G 1 or G 2 ; or C 1 -C 8 alkyl, C 2 -C 8 alkenyl, each optionally substituted; A is O, S or NR 7 ; R 2 is cyano, NR 8 —N═CR 9 R 10 or NC(═O)R 30 ; or a 5- or 6-membered heteroaromatic ring, each ring or ring system optionally substituted; R 3 is H, halogen, cyano, C 1 -C 6 alkyl; J is C 1 -C 8 alkyl or phenyl, optionally substituted; and R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 10 , R 19 , R 21 , R 30 , G 1 and G 2 are as defined in the disclosure.

  本发明涉及一种抑制不需要的动物细胞增殖的方法，该方法包括将动物细胞与公式1的化合物接触，以及其所有药学上可接受的盐、N-氧化物、水合物、溶剂化合物或其几何和立体异构体：其中，R1是NR4R5、N═CR19R21、OR6、G1或G2；或C1-C8烷基、C2-C8烯基，每个基团可选择性地被取代；A是O、S或NR7；R2是氰基、NR8—N═CR9R10或NC(═O)R30；或5-或6-成员杂环芳基环，每个环或环系统可选择性地被取代；R3是H、卤素、氰基、C1-C6烷基；J是C1-C8烷基或苯基，可选择性地被取代；以及R4、R5、R6、R7、R8、R9、R10、R19、R21、R30、G1和G2如所述。
• WO2007/149448
  申请人：——

  公开号：——

  公开（公告）日：——
• Tubulin modulating antifungal and antiproliferative pyrazinone derivatives
  作者：Andrew E. Taggi、Thomas M. Stevenson、James F. Bereznak、Paula L. Sharpe、Steven Gutteridge、Robert Forman、John J. Bisaha、Daniel Cordova、Martina Crompton、Lora Geist、Patrick Kovacs、Eric Marshall、Ritesh Sheth、Courtney Stavis、Chi-Ping Tseng

  DOI：10.1016/j.bmc.2015.08.038

  日期：2016.2

  A novel class of synthetic tubulin polymerization disruptors, based on a substituted pyrazin-2-one core, has been discovered. These molecules have proven to be potent broad spectrum fungicides, with activity on agriculturally important ascomycete and basidiomycete pathogens. They have also been found to be particularly potent against human rhabdomyosarcoma cells. Using an efficient synthetic route, the agricultural and medicinal activity was explored. (C) 2015 Elsevier Ltd. All rights reserved.