Development on the Synthesis of Phosphodieseterase Type 5 (PDE5) Inhibitors

Abstract:

Phosphodieseterase type 5 inhibitors are safe, efficacy and well tolerated in the treatment of erectile dysfunction and therefore widely used. In this paper, the various synthetic methods and development on the synthesis of sildenafil,vardenafil,tadalafil are evaluated.

• Periodical: Advanced Materials Research (Volume 749)
• Pages: 186-191
• DOI: https://doi.org/10.4028/www.scientific.net/AMR.749.186
• Online since: August 2013
• Authors: Yu Zhen Ma, Guang Zhou Zhang
• Keywords: PDE5 Inhibitors, Sildenafil, Synthesis, Tadalafil, Vardenafil

References

[1] Kling, J. From hypertension to angina to Viagra[J]. Modern Drug Discovery, 1998, 1: 31-38.

[2] Campbell, S. F. Science, art and drug discovery: a personal perspective[J]. Clinical Science, 2000, 99, 255-260.

DOI: 10.1042/cs0990255

[3] Bell A.S. Brown,D. Terrett N.K. Pyrazolopy-rimidinones antianginal agents[P]. EP463756(1992).

[4] Bell A.S. Brown,D. Terrett N.K. Pyrazolopyrimidinone antianginal agents [P]. US5250534（1993）.

[5] Terrett, N.K., Bell A.S. Brown,D. Ellis,P. Bioorg. Med. Chem. Lett. 1996, 6: 1819-1824.

[6] Dunn, P. J. Wood, A. S. Process for preparing sildenafil[P]. EP0812845 (1997).

[7] Liu Yuhui, Zhang Zhanbin. Method for preparing sildenafil [P]. CN01131151. 7(2001).

[8] Dunn P.J. Process for the preparation of pyrazolopyrimidinones [P]. WO 2001098284(2001).

[9] Xiong Zhenhu, Fei Xuening, Chang Kun. A New Synthesis of 1-Methyl-3-propylpyrazole-5-carboxlic Acid[J]. Chinese Journal of Synthetic Chemistry，2001，9（6）：443-556.

[10] DAI Huifang, WANG Honghua, XIONG Fangjun, CHEN Fener. Graphical Synthetic Routes of Sildenafil [J]. Chinese Journal of Pharmaceuticals，2010，41（12）：948-950.

[11] PETERJ D. Synthesis of commercial phosphodiesterase(V)inhibitors[J] . Organic Process Research & Development, 2005, 9(1): 88-97.

[12] Marc Nowakowski. Method for the production of 2-(2-ethoxyphenyl)-substituted imidazotriazinones[P]. US20040097505 (2004).

[13] Hatzimouratidis K, Hatzichristou D G. A comparative reviewof the options for treatment of erectile dysfunction: which treatment for whichpatient? [ J]. Drugs, 2005, 65(12) : 1621-1650.

DOI: 10.2165/00003495-200565120-00003

[14] Yao Shaobo, Cai Mingde, Lu Xiaoyi, Jiang Shende. Recent development on the synthesis of tadalafil [J]. Fine and Specialty Chemicals，2011，19（10）：37-44.

[15] Dugan A. Tetracylic derivatives, process of preparation and use[P]. US5859006(1999).

[16] Dugan A, Grondin P, Ruault C, et al. The discovery of tadalafil: a novel and highly selective PDE5 inhibitor. 2, 2, 3, 6, 7, 12, 12-α-hexahydropyrazino[1', 2'-1, 6-pyrido-3, 4-b] inbole-1, 4- dione [J]. J Med. Chem., 2003, 46: 4533-4542.

DOI: 10.1021/jm0300577

[17] Deshpande P B，Boda B B，Surti S S，et al. Process for the preparing tadalafil and its intermediate[P]. US7223863(2006).

[18] Bhushan L B, Bhushan L V, Indulal P S. Process for the preparing tadalafil and its intermediate[P]. WO2005068464(2005).

[19] Revell J D, Srinivasan N, Ganesan A. Two concise synthesis of cialis via the N-acyliminium Pictet Spengler reaction[J]. Synlett, 2004, 1428-1430.

DOI: 10.1055/s-2004-825625

[20] Orme M W, Martinelli M J, Doecke C W, et al. Modified Pictet-Spengler reaction and products prepared therefrom[P]. US7550479（2009）.