Add time:08/01/2019         Source:sciencedirect.com

In the rat, the highly potent anti-herpes drug (E)-5-(2-bromovinyl)-2′-deoxyuridine (BVdUrd) is rapidly converted to its base (E)-5-(2-bromovinyl)uracil (BVUra) through the action of pyrimidine nucleoside phosphorylases. However, BVdUrd can be regenerated or even generated de novo from BVUra by a pentosyl transfer reaction upon the administration of 2′-deoxythymidine (dThd), 2′-deoxyuridine (dUrd) or 5-ethyl-2′-deoxyuridine (EtdUrd). The antiherpetic drugs EtdUrd and 5-(2-chloroethyl)-2′-deoxyuridine (ClEtdUrd) can also be regenerated or generated de novo from their respective bases 5-ethyluracil (EtUra) and 5-(2-chloroethyl)uracil (ClEtUra), by a pentosyl transfer mediated by the administration of dThd or dUrd as deoxyribosyl donor. The generation or regeneration of BVdUrd, EtdUrd and ClEtdUrd from their bases (BVUra, EtUra and ClEtUra, respectively) is readily achieved because the latter have long half-lifes. Thus, the active anti-herpes drugs can be (re)generated repeatedly after a single administration of these nucleosides or their bases, followed by repeated administrations of dUrd.

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