期刊
ANTIVIRAL RESEARCH
卷 75, 期 1, 页码 1-13出版社
ELSEVIER
DOI: 10.1016/j.antiviral.2006.10.006
关键词
acyclic nucleoside phosphonates (ANPs); HPMPA; cidofovir (HPMPC); adefovir (PMEA); tenotovir (PMPA)
The collaboration between Antonin Holy [institute of Organic Chemistry and Biochemistry (IOCB, Prague, Czech Republic)] and Erik De Clercq (Rega Institute for Medical Research, K.U. Leuven, Belgium) started exactly 30 years ago. It led to the discovery of a (rather small) series of acyclic nucleoside analogues (prototype: DHPA), followed by the discovery of a large number of nucleotide analogues [acyclic nucleoside phosphonates (ANPs)] (prototype: HPMPA). From HPMPA originated three compounds, which have been approved by regulatory agencies worldwide for clinical use: (i) HPNIPC [cidofovir (Vistide (R))] for the treatment of cytomegalovirus (CMV) retinitis in AIDS patients, and off label for the treatment of polyoma-, papilloma-, adeno-, herpes- and poxvirus infections; (ii) PMEA [adefovir (in its oral prodrug form, adefovir dipivoxil (Hepsera (R))] for the treatment of chronic HBV (hepatitis B virus) infections, and (iii) PMPA (tenofovir (in its oral prodrug form, tenofovir disoproxil fumarate (Viread (R))] for the treatment of HIV infections (AIDS). The latter has also been approved, in combination with erntricitabine (Truvada (R)), and in combination with emtricitabine and efavirenz (Atripla (R)) for the treatment of HIV infections. Many other ANPs such as the DAP derivatives H PMPDAP, PMEDAP and PMPDAP, and the DAPy derivatives HPMPO-DAPy, PMEO-DAPy, and PMPO-DAPy, were found to exhibit an antiviral activity spectrum and potency comparable to that of the parent compounds HPMPA (and HPMPC), PMEA and PMPA, respectively. (C) 2006 Elsevier B.V. All rights reserved.
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