Anti-Retroviral and Pharmacological Properties of 9-(2-Phosphonylmethoxyethyl)Adenine (PMEA)
Acyclic nucleoside phosphonates (ANP) represent a structural class of compounds that contain a phosphonate group linked to an acyclic (alkyl) side chain of purine or pyrimidine bases.1-3 Due to the unusual direct linkage between the phosphor atom of the phosphonate moiety and a carbon atom of the acyclic side chain, the ANP derivatives are resistant to phosphorolytic cleavage by cellular esterases. Therefore, ANP derivatives are both enzymatically and chemically stable and are taken up by the cells in an unaltered intact form. Several subclasses of ANP can be considered (Fig. 1): (i) HPMP derivatives1, 4 [prototype compound: HPMPA, (S)-(3-hydroxy-2-Phosphonylmethyl propyl)adenine], (ii) PME derivatives1, 4, 5 [prototype compound: PMEA, 9-(2-Phosphonylmethoxyethyl)adenine], (iii) PMP derivatives6, 7 [prototype compounds: PMPA, (R)-9-(2-Phosphonylmethoxypropyl)adenine and FPMPA, (S)-9-(3-fiuoro-2-Phosphonylmethoxypropyl)adenine]. Each subclass of ANP is endowed with a specific and characteristic antiviral activity spectrum.
KeywordsAdenine Pyrimidine Purine Nucleoside Tritium
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