656247-18-6

• 常用中文名：尼达尼布乙基磺酸盐
• 常用英文名：Nintedanib Ethanesulfonate Salt
• CAS号：656247-18-6
• 分子式：C₃₃H₃₉N₅O₇S
• 分子量：649.757
• 相关类别： 有机原料 氨基化合物 磺酸类氨基化合物
• 发布时间：2018-06-08 23:03:52
• 更新时间：2026-07-02 11:21:38
• Nintedanib esylate (BIBF 1120 esylate) 是一种有效的 VEGFR1/2/3,FGFR1/2/3 和 PDGFRα/β 三重抑制剂,IC50 值分别为 34 nM/13 nM/13 nM,69 nM/37 nM/108 nM 和 59 nM/65 nM。

名称

• 中文名: (3Z)-2,3-二氢-3-[[[4-[甲基[2-(4-甲基-1-哌嗪基)乙酰]氨基]苯基]氨基]苯亚甲基]-2-氧代-1H-吲哚-6-甲酸甲酯乙磺酸盐
• 英文名: nintedanib esylate
• 中文别名: NINTEDANIB尼达尼布乙烷磺酸盐(3Z)-2,3-DIHYDRO-3-[[[4-[METHYL[2-(4-METHYL-1-PIPERAZINYL)ACETYL]AMINO]PHENYL]AMINO]PHENYLMETHYLENE]-2-OXO-1H-INDOLE-6-CBOXYLICACIDMETHYLESTERETHANESULFONATE; BIBF1120乙磺酸盐; Nintedanib esylate 活性化合物; (Z)-3-(((4-(N-甲基-2-(4-甲基哌嗪-1-基)乙酰氨基)苯基)氨基)(苯基)亚甲基)-2-氧代吲哚啉-6-羧酸甲酯乙磺酸盐; 乙磺酸尼达尼布,10 MM DMSO 溶液; BIBF1120 乙磺酸酯盐; 乙烷磺酸尼达尼布; INTEDANIB尼达尼布乙烷磺酸盐; 因达尼布乙磺酸盐; 抑制剂BIBF 1120 esylate; 【进口分装】Nintedanib ethanesulphonate/656-6; 尼达尼布乙磺酸盐杂质对照品; Intedanib尼达尼布乙烷磺酸盐 (3Z)-2,3-Dihydro-3-[[[4-[methyl[2-(4-methyl-1-piperazinyl)acetyl]amino]phenyl]amino]phenylmethylene]-2-oxo-1H-indole-6-cboxylic acid methyl ester ethanesulfonate; 尼达尼布单乙基磺酸盐; VEGFR/FGFR/PDGFR抑制剂(尼达尼布乙磺酸盐); 尼达尼布乙磺酸盐 656-6; 乙磺酸尼达尼布(API); 乙磺酸尼达尼布标准品; INTEDANIB|||乙磺酸尼达尼布|||BIBF 1120 (ESYLATE)|||尼达尼布乙磺酸盐|||NINTEDANIB ETHANESULFONATE SALT|||BIBF; 乙磺酸尼达尼布; 尼达尼布乙磺酸盐
• 英文别名: Intedanib ethanesulfonate; methyl (3S,5R)-3,5-di[(tert-butyldimethylsilyl)oxy]-1-hydroxy-cyclohexanecarboxylate; methyl (Z)-3-(((4-(N-methyl-2-(4-methylpiperazin-1-yl)acetamido)phenyl)amino)(phenyl)methylene)-2-oxoindoline-6-cboxylate ethanesulfonate; Ethanesulfonic acid - methyl (3Z)-3-{[(4-{methyl[(4-methyl-1-pipe razinyl)acetyl]amino}phenyl)amino](phenyl)methylene}-2-oxo-6-indo linecarboxylate (1:1); BIBF 1120 (esylate); 6-Benzofuranpropanenitrile,β-oxo; (Z)-Methyl 3-(((4-(N-methyl-2-(4-methylpiperazin-1-yl)acetamido)phenyl)amino)(phenyl)methylene; Nintedani; Nintedanib ethanesulfonate; (3S,5S)-3,5-Bis[[(1,1-dimethylethyl)dimethylsilyl]oxy]-1-hydroxy-cyclohexanecarboxylic Acid Methyl Ester; Trinidad Neeb ethanesulfonate; methyl (3S,5S)-3,5-bis[tert-butyl(dimethyl)silyloxy]-1-hydroxy-cyclohexanecarboxylate; Nintedanib ethanesulphonate; Ethanesulfonic acid - methyl (3Z)-3-{[(4-{methyl[(4-methyl-1-piperazinyl)acetyl]amino}phenyl)amino](phenyl)methylene}-2-oxo-6-indolinecarboxylate (1:1); Vargatef; BIBF-1120 esylate; 3-Z-[1-(4-(N-((4-methyl-piperazin-1-yl)-methylcarbonyl)-N-methyl-amino)-anilino)-1-phenyl-methylene]-6-methoxycarbonyl-2-indolinone monoethanesulphonate; Nintedanib Ethanesulfonate (Intedanib Ethanesulfonate); Methyl (3Z)-3-[({4-[N-methyl-2-(4-methylpiperazin-1-yl)acetamido]phenyl}amino)(phenyl)methylidene]-2-oxo-2,3-dihydro-1H-indole-6-carboxylate ethanesulfonate; methyl (3Z)-3-[({4-[N-methyl-2-(4-methylpiperazin-1-yl)acetamido]phenyl}amino)(phenyl)methylidene]-2-oxo-2,3-dihydro-1H-indole-6-carboxylate ethanesulfonate salt; Nintedanib ethanesulfonate salt; Nintedanib(ethanesulfonic acid); (3Z)-2,3-Dihydro-3-[[[4-[methyl[2-(4-methyl-1-piperazinyl)acetyl]amino]phenyl]amino]phenylmethylene]-2-oxo-1H-indole-6-cboxylic acid methyl ester ethanesulfonate; 3-Z-[1-(4-(N-((4-methyl-piperazin-1-yl)-methylcarbonyl)-N-methyl-amino)-anilino)-1-phenyl-methylene]-6-methoxycarbonyl-2-indolinone monoethanesulfonate salt; 3-Z-[1-(4-(N-((4-methyl-piperazin-1-yl)-methylcarbonyl)-N-methyl-amino)-anilino)-1-phenyl-ethylene]-6-methoxycarbonyl-2-indolinone monoethanesulfonate; UNII:42F62RTZ4G; nintedanib ethanesulfonate salt; BIBF 1120 esylate; Buprenorphine Impurity 24; (Z)Methyl 3-(((4-(N-methyl-2-(4-methyl-piperazin-1-yl)-acetcboxcboxcboxamido)phenyl)amino)(phenyl)methylene)-2-oxoindoline-6-cboxylate esylate; BIBF1120; BIBF 1120 BIBF-1120; NINTEDANIB ESYLATE. NINTEDANIB ETHANESULFONATE SALT; INTEDANIB; BRAND NAME OFEV. VGATEF; Nintedanib esylate, 10 mM in DMSO; Nintedanib esylate. Nintedanib ethanesulfonate salt; (Z)-methyl 3-(((4-(N-methyl-2-(4-methylpiperazin-1-yl)acetamido)phenyl)amino)(phenyl)methylene)-2-oxoindoline-6-cboxylate ethanesulfonate; Brand name OFEV. Vgatef; Nintedanib (Ofev); 1H-Indole-6-cboxylic acid, 2,3-dihydro-3-[[[4-[methyl[2-(4-methyl-1-piperazinyl)acetyl]amino]phenyl]amino]phenylmethylene]-2-oxo-, methyl ester, (3Z)-, ethanesulfonate (1:1); 1H-Indole-6-carboxylic acid, 2,3-dihydro-3-[[[4-[methyl[2-(4-methyl-1-piperazinyl)acetyl]amino]phenyl]amino]phenylmethylene]-2-oxo-, methyl ester, (3Z)-, compd. with ethanesulfonic acid (1:1); 3-Z-[1-(4-(N-((4-methyl-piperazin-1-yl)-methylcarbonyl)-N-methyl-amino)-anilino)-1-phenyl-methylene]-6-methoxycarbonyl-2-indolinone monoethanesulfonate; Nintedanib esylate; BIBF 1120 BIBF-1120; BIBF1120/nintedanib ethanesulfonate salt; Intedanib|||BIBF 1120 (esylate)|||Nintedanib Ethanesulfonate Salt|||BIBF; BIBF1120 ethanesulfonate salt; 1H-Indole-6-cboxylic acid,2,3-dihydro-3-[[[4-[methyl[(4-methyl-1-piperazinyl)acetyl]amino]phenyl]amino]-phenylmethylene]-2-oxo-, methylester, (3Z)-, ethanesulfonate (1:1); Trinidad Neeb esylate

物化性质

• 分子式: C₃₃H₃₉N₅O₇S
• 分子量: 649.757
• 精确质量: 649.257019
• PSA: 160.46000
• LogP: 4.62470
• 外观性状: 粉末
• 储存条件: -20℃

生物活性

• 描述: Nintedanib esylate (BIBF 1120 esylate) 是一种有效的 VEGFR1/2/3,FGFR1/2/3 和 PDGFRα/β 三重抑制剂,IC50 值分别为 34 nM/13 nM/13 nM,69 nM/37 nM/108 nM 和 59 nM/65 nM。
• 相关类别:
  信号通路 >> 蛋白酪氨酸激酶 >> FGFR
  信号通路 >> 蛋白酪氨酸激酶 >> PDGFR
  研究领域 >> 癌症
• 靶点:

  VEGFR1:34 nM (IC50)

  VEGFR2:13 nM (IC50)

  VEGFR3:13 nM (IC50)

  FGFR1:69 nM (IC50)

  FGFR2:37 nM (IC50)

  FGFR3:108 nM (IC50)

  PDGFRα:59 nM (IC50)

  PDGFRβ:65 nM (IC50)

• 体外研究: Nintedanib(BIBF 1120)与激酶结构域的氨基和羧基末端裂片之间的裂缝中的ATP结合位点结合。 Nintedanib(BIBF 1120)在细胞试验中抑制PDGF-BB刺激的BRP的增殖,EC50为79nM。在用5％血清加PDGF-BB刺激后,Nintedanib(BIBF 1120)(100nM)阻断MAPK的活化。 Nintedanib(BIBF 1120)可阻止PDGF-BB刺激增殖,在人血管平滑肌细胞(HUASMC)培养物中EC50为69 nM [1]。
• 体内研究: Nintedanib(BIBF 1120)(25-100mg/kg每日口服)在所有肿瘤模型中具有高活性,包括在裸鼠中生长的人肿瘤异种移植物和同系大鼠肿瘤模型。这在3天后肿瘤灌注的磁共振成像中显而易见,5天后血管密度和血管完整性降低,并且生长受到严重抑制[1]。 Nintedanib(BIBF 1120)可口服,在体内肿瘤模型中显示出令人鼓舞的功效,同时耐受性良好[2]。
• 动物实验: 使用5周龄至6周龄的无胸腺NMRI-nu / nu雌性小鼠（21-31g）进行测定。适应环境后，将小鼠用1至5×106（100μL）FaDu，Caki-1，SKOV-3，H460，HT-29或PAC-120细胞接种到动物的右侧腹部。适应环境后，将F344 Fischer大鼠用5×106（100μL）GS-9L细胞皮下注射到动物的右侧腹部。对于药代动力学分析，在小鼠眶后丛的指定时间点分离血液，并使用高效液相色谱 - 质谱法[1]分析血浆。
• 参考文献:

  [1]. Hilberg F, et al. BIBF 1120: triple angiokinase inhibitor with sustained receptor blockade and good antitumor efficacy. Cancer Res, 2008, 68(12), 4774-4782.

  [2]. Roth GJ, et al. Design, synthesis, and evaluation of indolinones as triple angiokinase inhibitors and the discovery of a highly specific 6-methoxycarbonyl-substituted indolinone (BIBF 1120). J Med Chem, 2009, 52(14), 4466-4480.

  [3]. Suzuki N, et al. Effect of a novel oral chemotherapeutic agent containing a combination of trifluridine, tipiracil and the novel triple angiokinase inhibitor nintedanib, on human colorectal cancer xenografts. Oncol Rep. 2016 Dec;36(6):3123-3130.

合成路线

656247-17-5 594-45-6 ~96% 656247-18-6

文献：BOEHRINGER INGELHEIM INTERNATIONAL GMBH Patent: WO2009/71523 A1, 2009 ; Location in patent: Page/Page column 4; 25-27 ;

上下游产品

上游产品  2
656247-17-5 594-45-6
下游产品  0