以2-氨基-5-硝基苯酚为原料经过酚羟基烷基化、氨基甲磺酰化、硝基还原为氨基后,进行溴乙酰化以及N-烷基化5步反应制得了三羰基锝标记配体基:N-[2-环己基甲氧基-4(1-(2,2'-二吡啶甲基)胺基)乙酰胺基]苯基甲磺酰胺(NSC-PA),并对反应条件进行了优化.中间体及目标化合物经红外、质谱和核磁共振氢谱进行了结构表征,HPLC法测定最终产物的纯度大于98%.该目标化合物可以作为三羰基锝标记前体,为进一步开发乳腺癌显像药物奠定了基础.
参考文献
[1] | Su B,Diaz-Cruz E S,Landini S,et al.Novel Sulfonanilide Analogues Suppress Aromatase Expression and Activity in Breast Cancer Cells Independent of COX-2 Inhibition[J].J Med Chem,2006,49(4):1413-1419. |
[2] | Su B,Landini S,Davis,D D,et al.Synthesis and Biological Evaluation of Selective Aromatase Expression Regulators in Breast Cancer Cells[J].J Med Chem,2007,50:1635-1644. |
[3] | Su B,Tian R,Darby M V,et al.Novel Sulfonanilide Analogs Decresse Aromatase Activity in Breast Cancer Cells:Synthesis,Biological Evaluation and Ligand-Based Pharmacophore Identification[J].J Med Chem,2008,51:1126-1135. |
[4] | Brueggemeier R W,Su B,Darby M V,et al.Selective Regulation of Aromatase Expression for Drug Discovery[J].J Steroid Biochem Mol Biol,2009,11:9. |
[5] | Wang M,Lacy G,Gao Mingzhang,et al.Synthesis of Carbon-11 Labeled Sulfonanilide Analogues as New Potential PET Agents for Imaging of Aromatase in Breast Cancer[J].Bioorg Med Chem,2007,17:332-336. |
[6] | Alberto R,Schibli R,Egli A,et al.A Novel Organometallic Aqua Complex of Technetium for the Labeling of Biomolecules:Synthesis of[99mTc(H2O)3(CO) 3]+ from[99m TcO4]-in Aqueous Solution and Its Reaction with a Bifunctional Ligand[J].J Med Chem,1998,12:7987-7988. |
[7] | ZHANG Xiaobo,ZHU Lin,ZHAO Xueying,et al.Research of Novel Bifunctional Chelating Agents for the Tc-tricarbonyls Precursor 99mTc(CO) 3 (H2O)3]+[J].J Nucl Radiochem,2004,26(1):11-17(in Chinese).张小波,朱霖,赵学颖,等.[99mTc(CO)3(H2O)3]+标记的新双功能联接剂的研究[J].核化学与放射化学,2004,26(1):11-17. |
[8] | ZHANG Xianzhong,WANG Xuebin,WEN Haitao.The Preparation and Biodistribution of a New Potential Myocardial Imaging Agent:Technetium-99m Labeled[Tc(CO)3(TBI)3]Complex[J].Chem J Chinese Univ,2003,24(1):21-24(in Chinese).张现忠,王学斌,温海涛.一种新的潜在心肌显像剂[99mTc(CO)3(TBI)3]+的制备及其生物分布研究[J].高等学校化学学报,2003,24(1):21-24. |
[9] | JIANG Yan,LIU Boli.A New Potential Myocardial Imaging Agent:Technetium-99m Labeled[Tc(CO)3 (MIBI)3]+Complex[J].Chinese Sci Bull,2001,46(9):727-730(in Chinese).蒋燕,刘伯里.一种新的99mTc标记的[Tc(CO)3 (MIBI)3]+络合物作为心肌显像剂[J].科学通报,2001,46(9):727-730. |
[10] | Liu Y,Spingler B,Schmutz P,et al.Metal-mediated Retro Diels-Alder of Dicyclopentadiene Derivatives:a Convenient Synthesis of[(Cp-R)M(CO)3](M =99mTc,Re) Complexes[J].JAm Chem Soc,2008,130(5):1554-1555. |
[11] | Muller C,Schubiger P A,Schibli R.Synthesis and in Vitro/in Vivo Evaluation of Novel 99mTc (CO)3-Folates[J].Bioconjugate Chem,2006,17(3):797-800. |
[12] | Alberto R,Ortner K,Wheatley N,et al.Synthesis and Properties of Boranocarbonate:A Convenient in Situ CO Source for the Aqueous Preparation of[99mTc(OH2)3(CO)3]+[J].J Am Chem Soc,2001,123(3):3135-3136. |
[13] | Julemont F,Leval X,Michaux C,et al.Spectral and Crystallographic Study of Pyridinic Analogues of Nimesulide:Determination of the Active Form of Methanesulfonamides as COX-2 Selective Inhibitorsl[J].J Med Chem,2002,45:5182-5185. |
[14] | WANG Fei,KUANG Fei.Progress of Tumor Molecular Imaging Study[J].J Pract Oncol,2006,3 (21):206-208 (in Chinese).王飞,邝菲.肿瘤分子影像学研究进展[J].实用肿瘤杂,2006,3(21):206-208. |
[15] | LOU Yongjun,DONG Jinhua,XU Liying,et al.Synthesis and Anti-inflammatory Activity of N-(4-arylamidophenyl) methanesulfonamide Aerivatives[J].Acta Pharrm Sin,2004,39(7):518-520(in Chinese).楼永军,董金华,徐莉英,等.N-(4-芳酰胺基苯基)甲磺酰胺类化合物的合成及抗炎活性[J].药学学报,2004,39(7):518-520. |
[16] | WEI Peipei.Synthesis Research of Iguratimod[D].Nanjing:Nanjing University of Science and Technology,2009 (in Chinese).魏佩佩.艾拉莫德的合成研究[D].南京:南京理工大学,2009. |
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%