以7-脱氧胆酸(1)为原料,由Jones试剂氧化得到3,12-二氧代-7-脱氧胆酸(2),然后与双(2-氯乙基)胺反应,得到3,12-二氧代-N,N-双(2-氯乙基)-7-脱氧胆酰胺(4),进一步通过对化合物4中的3-位羰基进行官能团转换,得到2个3-位分别被肟基、缩胺硫腙基取代的12-氧代-N,N-双(2-氯乙基)-7-脱氧胆酰胺类型化合物.同时,初步测试了合成物对肿瘤细胞增殖抑制活性,结果表明,化合物对宫颈癌细胞的生长有显著的抑制活性.
参考文献
| [1] | Trafalis D T P,Camoutsisa C,Papageorgiou A.Research on the Anti-tumour Effect of Steroid Lactam Alkylator (NSC-294859) in Comparison with Conventional Chemotherapeutics in Malignant Melanoma[J].Melanoma Res,2005,15:273-281. |
| [2] | Papageorgiou A,Koutsourea A I,Arsenoua E S,et al.Structure-anti-leukemic Activity Relationship Study of B-and D-ring Modified and Non-modified Steroidal Esters of Chlorambucil's Active Metabolite[J].Anti-Cancer Drugs,2005,16:1075-1083. |
| [3] | Karapidaki I,Papageorgiou A,Geromichalos G,et al.Cytogenetic and Antineoplastic Effects of Modified Steroidal Alkylators[J].Genet Test Mol Biomarkers,2010,14(1):93-97. |
| [4] | Karapidaki I,Bakopoulou A,Papageorgiou A,et al.Genotoxic,Cytostatic,Antineoplastic and Apoptotic Effects of Newly Synthesized Antitumour Steroidal Esters[J].Mutat Res,2009,675:51-59. |
| [5] | Koutsourea A I,Fousteris M A,Arsenou E S.Synthesis,In Vivo Antileukemic Evaluation and Comparative Study of Novel 5·-7-Keto Steroidal Esters of Chlorambucil and Its Active Metabolite[J].In Vivo,2008,22:345-352. |
| [6] | Shervington L A,Smith N,Norman E,et al.To Determine the Cytotoxicity of Chlorambucil and One of Its Nitro-derivatives,Conjugated to Prasterone and Pregnenolone,Towards Eight Human Cancer Cell-lines[J].Eur J Med Chem,2009,44:2944-2951. |
| [7] | Gupta A,Saha P,Desc(o)teaux C C,et al.Design,Synthesis and Biological Evaluation of Estradiol Chlorambucil Hybrids as Anticancer Agents[J].Bioorg Med Chem Lett,2010,20:1614-1618. |
| [8] | Zhang H B,Xu J J,Zhao X L,et al.Synthesis and Biological Evalution of Novel Steroid-linked Nitrogen Mustards[J].Chinese Chem Lett,2009,20:680-683. |
| [9] | Camoutsis C,Trafalis D,Pairas G,et al.On the Formation of 4-[N,N-Bis (2-chloroethyl)-amino]phenyl Acetic Acid Esters of Hecogenin and Aza-homo-hecogenin and Their Antileukemic Activity[J].Il Farmaco,2005,60:826-829. |
| [10] | Cui J G,Fan L,Huang L L,et al.Synthesis and Evaluation of Some Steroidal Oximes as Cytotoxic Agents:Structure/activity Studies(Ⅰ)[J].Steroids,2009,74(1):62-72. |
| [11] | Huang Y M,Chen S J,Cui J G,et al.Synthesis and Cytotoxicity of A-homo-lactam Derivatives of Cholic Acid and 7-Deoxycholic Acid[J].Steroids,2011,76:690-694. |
| [12] | Huang Y M,Cui J G,Zhong Z G,et al.Synthesis and Cytotoxicity of 17a-Aza-D-homo-androster-17-one Derivatives[J].Bioorg Med Chem Lett,2011,21:3641-3643. |
| [13] | Huang Y M,Cui J G,Chen S G,et al.Synthesis and Antiproliferative Activity of Some Steroidal Lactams[J].Steroids,2011,76:1346-1350. |
| [14] | Gan C F,Cui J G,Huang Y M,et al.Synthesis and Antiproliferative Activity of Some Steroidal Lactone Compounds[J].Stemids,2012,77:255-259. |
| [15] | Gan C F,Fan L H,Cui J G,et al.Synthesis and in vitro Antiproliferative Evaluation of Some Ring B Abeo-sterols[J].Steroids,2012,77:1061-1068. |
| [16] | Christy Hunter A,Priest S M.An Efficient One-pot Synthesis Generating 4-ene-3,6-Dionefunctionalised Steroids from Steroidal 5-en-3-ols Using Amodified Jones Oxidation Methodology[J].Steroids,2006,71:30-33. |
| [17] | SU Shaoyang,LIN Qifu,GAN Chunfang,et al.Reasearch Progress of Steroidal Nitrogen Mustard Compounds with Anticancer Activity[J].Chemistry,2012,75(5):414-419(in Chinese).苏绍烊,林啟福,甘春芳,等.具有抗肿瘤活性甾体氮芥类化合物的研究进展[J].化学通报,2012,75(5):414-419. |
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