研究了1-(4-氯苯胺基)4-(4-吡啶甲基)-2,3-二氮杂萘琥珀酸盐的合成工艺,采用苯酞和吡啶甲醛为起始原料,经加成、重排、取代和成盐4步反应得到目标化合物.中间体及目标化合物通过1H NMR、MS和HPLC进行了表征.重结晶纯化后的目标化合物纯度为98.1%.对荷瘤(人大肠癌HT 29细胞)裸鼠的抑癌活性测定表明,该化合物具有明显的抑制肿瘤生长作用.
参考文献
[1] | Folkman J.Anti-Angiogenesis:New Concept for Therapy of Solid Tumors[J].Ann Surg,1972,(175):409-416. |
[2] | Folkman J.Fighting Cancer by Attacking Its Blood Supply[J].Sci Am,1996,275:150-154. |
[3] | Ferraar N.Vascular Endothelial Growth Factor Basic Science and Clinical Progress[J].Endocr Rev,2004,25 (4):581-611. |
[4] | Leenders W P J.Targetting VEGF in Antiangiogenic and Anti-tumour Therapy:Where are We Now[J].Int J Exp Pathol,1998,(79):339-346. |
[5] | Jocelyn Holash,Sam Davis,Nick Papadopoulos,et al.VEGF-Trap:A VEGF Blocker with Potent Antitumor Effects[J].PNAS,2002,99(17):11393-11398. |
[6] | Naoyuki Murata,Yuuki Takashima,et al.Anti-tumor Effects of Anti-VEGF siRNA Encapsulated with PLGA Microspheres in Mice[J].Controlled Release,2008,126 (3):246-254. |
[7] | Bold G,Frel J,Traxier P,et al.Phthalazines with Angiogenesis Inhibiting Activity:US,2003/0191129 Al[P],2003. |
[8] | Lu H Y,Klein R S,Schwartz E L.Anti-angiogenic and Anti-tumor Activity of AEAC,a Novel Small Molecule Inhibitor of Thymidine Phosphorylase,in Combination with the VEGF-Trap[J].Clin Cancer Res,2009,15(16):5136-5144. |
[9] | WANG Jianing,CHEN Guanhong,LIU Kechun,et al.Synthesis and Application of 1-(4-Chloro chloroaniline)-4-(4-pyridylmethyl)-2,3-benzodiazi:CN,200610045239.6[P],2006 (in Chinese).王加宁,陈贯虹,刘可春,等.1-(4-氯苯胺基)-4-(4-甲基吡啶基)-2,3-二氮杂萘的合成与应用:中国,200610045239.6[P],2006. |
[10] | Bold G,Altmann K H,Frel J,et al.New Anilinophthalazines as Potent and Orally Well Absorbed Inhibitors of the VEGF Receptor Tyrosine Kinases Useful as Antagonists of Tumor-Driven A ngiogenesis[J].J Med Chem,2000,(43):2310-2323. |
[11] | LU Fei,SHEN Hongxun,CHEN Ruixin,et al.Development of a Human Colon Carcinoma Liver Metastases Model and Expression of CK20 mRNA in Blood of Nude Mice[J].Acta Acad Med Nantong,2002,22(1):22-23.陆飞,沈洪薰,陈瑞新,等.人结肠癌细胞裸鼠肝转移模型及其血中CK20 mRNA表达的研究[J].南通医学院学报2002,22(1):22-23. |
上一张
下一张
上一张
下一张
计量
- 下载量()
- 访问量()
文章评分
- 您的评分:
-
10%
-
20%
-
30%
-
40%
-
50%