Pertusati Fabrizio, Serpi Michaela, McGuigan Christopher
Welsh School of Pharmacy, Cardiff University, Cardiff, UK.
Antivir Chem Chemother. 2012 May 14;22(5):181-203. doi: 10.3851/IMP2012.
Considerable attention has been focused on the development of phosphonate-containing drugs for application in many therapeutic areas. However, phosphonate diacids are deprotonated at physiological pH and thus phosphonate-containing drugs are not ideal for oral administration, an extremely desirable requisite for the treatment of chronic diseases. To overcome this limitation several prodrug structures of biologically active phosphonate analogues have been developed. The rationale behind the design of such agents is to achieve temporary blockade of the free phosphonic functional group until their systemic absorption and delivery, allowing the release of the active drug only once at the target. In this paper, an overview of acyclic and cyclic nucleoside phosphonate prodrugs, designed as antiviral agents, is presented.
含膦酸盐药物在许多治疗领域的应用开发已受到广泛关注。然而，膦酸二在生理pH值下会发生去质子化，因此含膦酸盐药物并非口服给药的理想选择，而口服给药是治疗慢性病极为需要的必要条件。为克服这一局限性，已开发出几种具有生物活性的膦酸盐类似物的前药结构。设计此类药物的基本原理是实现对游离膦酸官能团的暂时阻断，直至其被全身吸收和递送，从而使活性药物仅在靶点处释放一次。本文概述了设计用作抗病毒剂的非环状和环状核苷膦酸酯前药。
