title: Recent progress in prodrug design strategies based on generally applicable modifications.
abstract: The development of prodrugs has progressed with the aim of improving drug bioavailability by overcoming various barriers that reduce drug benefits in clinical use, such as stability, duration, water solubility, side effect profile, and taste. Many conventional drugs act as the precursors of an active agent in vivo; for example, the anti-HIV agent azidothymidine (AZT) is converted into its corresponding active triphosphate ester in the body, meaning that AZT is a prodrug in the broadest sense. However prodrug design is generally difficult owing to the lack of general versatility. Thus, these prodrugs, broadly defined, are often discovered by chance or trial-and-error. Recently, many prodrugs that could release the corresponding parent drugs with or without enzymatic action under physiological conditions have been reported. These prodrugs can be easily designed and synthesized because of their generally applicable modifications. This digest paper provides an overview of recent development in prodrug strategies for drugs with a carboxylic acid or hydroxyl/amino group on the basis of a generally applicable modification strategy, such as esterification, amidation, or benzylation.
authors.affiliation: Faculty of Frontiers of Innovative Research in Science and Technology, Konan University, Minatojima-minamimachi, Chuo, Kobe 650-0043, Japan; Faculty of Pharmaceutical Sciences, Kobe Pharmaceutical University, Motoyamakita, Higashinada, Kobe 658-8558, Japan. Electronic address: pynden@gmail.com.
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Hamada
mesh_terms: D000577:Amides / Q000737:chemistry / Q000378:metabolism / Q000493:pharmacokinetics; D000818:Animals; D019380:Anti-HIV Agents / Q000737:chemistry* / Q000378:metabolism / Q000493:pharmacokinetics*; D001593:Benzyl Compounds / Q000737:chemistry / Q000378:metabolism / Q000493:pharmacokinetics; D001682:Biological Availability; D002264:Carboxylic Acids / Q000737:chemistry / Q000378:metabolism / Q000493:pharmacokinetics; D015195:Drug Design; D004951:Esterification; D006678:HIV / Q000187:drug effects; D015658:HIV Infections / Q000188:drug therapy; D006801:Humans; D011355:Prodrugs / Q000737:chemistry* / Q000378:metabolism / Q000493:pharmacokinetics*; D012995:Solubility; D015215:Zidovudine / Q000031:analogs & derivatives / Q000378:metabolism / Q000493:pharmacokinetics
chemical_list: D000577:Amides; D019380:Anti-HIV Agents; D001593:Benzyl Compounds; D002264:Carboxylic Acids; D011355:Prodrugs; D015215:Zidovudine
keywords: Bioavailability; Enzyme; Prodrug; Spontaneous cleavage; Water solubility