The prodrugs of L-guanosine analogs: design, synthesis and anti-HIV activity

doi:10.5246/jcps.2011.04.041

• Full Papers • Previous Articles Next Articles

The prodrugs of L-guanosine analogs: design, synthesis and anti-HIV activity

Jun-Feng Lu, Lu-Jia Xie, Mou Cao, Zhu Guan^*, Ying Guo, Zhen-Jun Yang^*, Li-He Zhang

1. State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University Health Science Center, Beijing 100191, China
2. Institute of Meteria Medica, Chinese Academy of Medical Science, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China

Received:2011-01-12 Revised:2011-04-20 Online:2011-07-01 Published:2011-07-01
Contact: Zhu Guan*, Zhen-Jun Yang*

Abstract

Abstract: To improve the stability and pharmacokinetic properties, prodrugs of L-ddG (L-2',3'-dideoxy-guanosine) and L-D4G (L-2',3'-dihydro-2',3'-dideoxyguanosine) modified with a series of substituted amino groups at C-6 position of the purine base were designed and synthesized and their anti-HIV activities were evaluated. Compounds 7d and 8g exhibited moderate activity and showed EC50 of 42 μmol/L and 55 μmol/L, respectively.

Key words: L-ddG, L-D4G, Prodrug, Anti-HIV

CLC Number:

R916

Supporting:

Jun-Feng Lu, Lu-Jia Xie, Mou Cao, Zhu Guan^*, Ying Guo, Zhen-Jun Yang^*, Li-He Zhang. The prodrugs of L-guanosine analogs: design, synthesis and anti-HIV activity [J]. , DOI: 10.5246/jcps.2011.04.041.

[1]	Yiben Lu, Miao Zhang, Yongjun Zheng, Xinyu Hou, Muye He, Kaiyan Lou, Feng Gao. Redox-responsive self-assembly polymeric micelles based on mPEG-β-cyclodextrin and a camptothecin prodrug as drug release carriers [J]. Journal of Chinese Pharmaceutical Sciences, 2021, 30(12): 941-955.
[2]	Meng Wang, Lei Xing, Shifang Lu, Zhu Guan^*, Zhenjun Yang, Lihe Zhang. Synthesis and the anti-HIV activity of novel dinucleotides containing L-isonucleosides [J]. , 2013, 22(4): 314-318.
[3]	Junchao Shao, Haixia Lin^*, Yongmei Cui, Shaoman Yin, Erwin G Van Meir, Jiachen Huang. Design, synthesis and evaluation of the cytotoxicity of a N-mustard and paclitaxel conjugate prodrug [J]. , 2013, 22(2): 137-143.
[4]	Li-Qiang Han, Yu-An Zhang, Shu-Yang Yao, Bo Xu, Ze-Mei Ge, Jing-Rong Cui, Run-Tao Li^* . Study of the prodrugs of peptide aldehydes as proteasome inhibitors [J]. , 2012, 21(1): 21-27.
[5]	Qing Yang, Ji-Rang Zhu, Qi Sun^, Jing-Rong Cui, Run-Tao Li, Ze-Mei Ge^ . A novel class of cyclophosphamide prodrug: structure-activity relationships of cyclophosphamide piperaziniums [J]. , 2010, 19(1): 24-33.
[6]	ZHOU Jiang-quan, TANG Zhi-qiang^*. Cytochrome P450 Directed Prodrug Activation Therapy in Research of Cancer Enzymology [J]. , 2005, 14(1): 1-9.
[7]	LIU Yi, YANG Zhen-jun^*, BOUDINOT F.Douglas, CHU Chung Kuang, ZHANG Li-he . Pharmacokinetics and Bioavailability of 2-Amino-6-Cyclopropylamino-9-(2,3-Dideoxy-β-D-glyceropent-2-enofuranosyl) Purine (Cyclo-D4G) in Rats [J]. , 2004, 13(1): 37-41.
[8]	LIU Yi, YANG Zhen-jun^*, Boudinot F Douglas, CHU Chang kuang, ZHANG Li-he . Determination of 2-Amino-6-Cyclopropylamino-9-(2,3-Dideoxy-β-D-glyceropent-2-enofuranosyl)purine in Rat Plasma, Urine and Liver Homogenates by High Performance Liquid Chromatography [J]. , 2003, 12(2): 93-97.

The prodrugs of L-guanosine analogs: design, synthesis and anti-HIV activity

PDF (PC)

Knowledge

Cited

Abstract

Cite this article

share this article

References

Related Articles 8

Recommended Articles

Metrics

Comments