(2Z)-3-dimethylamino-2-(1H-indole-3-carbonyl)acrylonitrile | 928203-37-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: (2Z)-3-dimethylamino-2-(1H-indole-3-carbonyl)acrylonitrile
• 英文别名: (Z)-3-(dimethylamino)-2-(1H-indole-3-carbonyl)prop-2-enenitrile
• CAS: 928203-37-6
• 化学式: C₁₄H₁₃N₃O
• 分子量: 239.277
• InChiKey: MVQNRLYQOQCWJJ-KTKRTIGZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  18
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  59.9
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (2Z)-3-dimethylamino-2-(1H-indole-3-carbonyl)acrylonitrile 在 sodium hydroxide 、 硫酸 、 potassium carbonate 作用下， 以 乙醇 为溶剂， 反应 24.0h， 生成 [4-(1H-吲哚-3-基)嘧啶-2-基]胺
  参考文献：
  名称：

  Synthesis and antitumor activity of indolylpyrimidines: Marine natural product meridianin D analogues

  摘要：

  Marine indole alkaloid meridianin D analogues have been synthesized starting from the appropriate 3-cyanoacetyl indole. A facile two-step conversion of 3-cyanoacetyl indole to the corresponding cyano meridianin D analogue by treatment with dimethylformamide-dimethylacetal and further cyclization of the resulting enaminonitrile with antinoguanidine is described. Then, alkaline hydrolysis of cyano meridianin D afforded the carboxylic acid analogue. The treatment of acid with 75% H2SO4 afforded the desired 6-debromomeridianin D. Simply treatment of cyano meridianin D analogue with hydrazine hydrate afforded the amidrazone analogue. The biological evaluation indicated that cyano analogue showed good cytotoxic activity with IC50 values of 0.85 and 2.65 g (against MCF7 and HeLa, respectively), but acid and amidrazone analogues showed high cytotoxicity with IC50 values of 0.75 and 0.25 mu g, respectively (against MCF7). (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2006.11.023
• 作为产物：
  描述：

  3-(1H-吲哚-3-基)-3-氧丙腈 、 N,N-二甲基甲酰胺二甲基缩醛 以 甲苯 为溶剂， 反应 0.25h， 以84.5%的产率得到(2Z)-3-dimethylamino-2-(1H-indole-3-carbonyl)acrylonitrile
  参考文献：
  名称：

  Synthesis and antitumor activity of indolylpyrimidines: Marine natural product meridianin D analogues

  摘要：

  Marine indole alkaloid meridianin D analogues have been synthesized starting from the appropriate 3-cyanoacetyl indole. A facile two-step conversion of 3-cyanoacetyl indole to the corresponding cyano meridianin D analogue by treatment with dimethylformamide-dimethylacetal and further cyclization of the resulting enaminonitrile with antinoguanidine is described. Then, alkaline hydrolysis of cyano meridianin D afforded the carboxylic acid analogue. The treatment of acid with 75% H2SO4 afforded the desired 6-debromomeridianin D. Simply treatment of cyano meridianin D analogue with hydrazine hydrate afforded the amidrazone analogue. The biological evaluation indicated that cyano analogue showed good cytotoxic activity with IC50 values of 0.85 and 2.65 g (against MCF7 and HeLa, respectively), but acid and amidrazone analogues showed high cytotoxicity with IC50 values of 0.75 and 0.25 mu g, respectively (against MCF7). (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2006.11.023

文献信息

• [EN] AMINOPYRIMIDINE DERIVATIVES AS JNK INHIBITORS<br/>[FR] DERIVES D'AMINOPYRIMIDINE EN TANT QU'INHIBITEURS DE LA JNK
  申请人：CELLTECH R&D LTD

  公开号：WO2006038001A1

  公开（公告）日：2006-04-13

  A compound of formula (I) or a pharmaceutically acceptable salt, solvate or N-­oxide thereof: wherein A represents a pyrrole, pyrazole, imidazole or triazole ring; B represents a benzene, pyridine or pyrimidine ring; M represents the residue of an azetidine, pyrrolidine or piperidine ring; E represents a covalent bond or an optionally substituted straight or branched alkylene chain containing from 1 to 4 carbon atoms; Z represents hydrogen, -CORa, -C02Rb, -CONKc Rd, -CONRcORb, -COCO2Rb, - COCONRcRd, -COCH2NRcRd, -COCH2NRcCONKcRd, COCH2NRcCO2Rb, -NRcCORa, - NRcCO2Rb, -NRcCONRcRd, -S02Re, -SO2NRcRd or -SO2NRcC02Rb; or Z represents an optionally substituted phenyl, heteroaryl or C3-7 heterocycloalkyl group; R1 and R2 independently represent hydrogen, halogen, cyano, nitro, C1-6 alkyl, trifluoromethyl, hydroxy, C1-6 alkoxy, difluoromethoxy, trifluoromethoxy, C1-6 alkylsulphonyl, amino, C1-6 alkylamino, di(C1-6)alkylamino, aminocarbonyl or C2-6 alkoxycarbonyl; R3 represents hydrogen, C1-6 alkyl, -CH2CONRcRd or -SO2Re; R4 represents hydrogen, C1-6 alkoxy, oxo, -CO2Rb or -CONKcRd. The compounds of the present invention are potent inhibitors of JNK.

  式（I）的化合物或其药学上可接受的盐、溶剂或N-氧化物：其中A代表吡咯、吡唑、咪唑或三唑环；B代表苯、吡啶或嘧啶环；M代表氮杂环丙烷、吡咯丙烷或哌啶环的残基；E代表共价键或含有1至4个碳原子的可选取代的直链或支链烷基链；Z代表氢、-CORa、-C02Rb、-CONKcRd、-CONRcORb、-COCO2Rb、-COCONRcRd、-COCH2NRcRd、-COCH2NRcCONKcRd、COCH2NRcCO2Rb、-NRcCORa、-NRcCO2Rb、-NRcCONRcRd、-S02Re、-SO2NRcRd或-SO2NRcC02Rb；或Z代表可选取代的苯基、杂环芳基或C3-7杂环烷基基团；R1和R2独立地代表氢、卤素、氰基、硝基、C1-6烷基、三氟甲基、羟基、C1-6烷氧基、二氟甲氧基、三氟甲氧基、C1-6烷基磺酰基、氨基、C1-6烷基氨基、二(C1-6)烷基氨基、氨基甲酰基或C2-6烷氧羰基；R3代表氢、C1-6烷基、-CH2CONRcRd或-SO2Re；R4代表氢、C1-6烷氧基、氧代、-CO2Rb或-CONKcRd。本发明的化合物是JNK的有效抑制剂。
• Synthesis and antitumor activity of indolylpyrimidines: Marine natural product meridianin D analogues
  作者：Mohamed A.A. Radwan、Mahmoud El-Sherbiny

  DOI：10.1016/j.bmc.2006.11.023

  日期：2007.2.1

  Marine indole alkaloid meridianin D analogues have been synthesized starting from the appropriate 3-cyanoacetyl indole. A facile two-step conversion of 3-cyanoacetyl indole to the corresponding cyano meridianin D analogue by treatment with dimethylformamide-dimethylacetal and further cyclization of the resulting enaminonitrile with antinoguanidine is described. Then, alkaline hydrolysis of cyano meridianin D afforded the carboxylic acid analogue. The treatment of acid with 75% H2SO4 afforded the desired 6-debromomeridianin D. Simply treatment of cyano meridianin D analogue with hydrazine hydrate afforded the amidrazone analogue. The biological evaluation indicated that cyano analogue showed good cytotoxic activity with IC50 values of 0.85 and 2.65 g (against MCF7 and HeLa, respectively), but acid and amidrazone analogues showed high cytotoxicity with IC50 values of 0.75 and 0.25 mu g, respectively (against MCF7). (c) 2006 Elsevier Ltd. All rights reserved.