Page - (000217) - in Biomedical Chemistry: Current Trends and Developments

• Extensive array of synthetic amino acids • α-Amine and α-carboxylic groups • Side chain functional groups e.g. amine, carboxylic acid, alcohol, and thiol • Commonly used linkage chemistry between amino acid and parent including ester, amide, carbonate and carbamate bonds • Large number of amino acid suppliers available • Amino acids are building blocks for proteins and are generally regarded as safe • Can potentially target carrier-mediated transporters for improved delivery across cell membranes • Many amino acid prodrugs have been commercially developed and help patients • Commercial and regulatory precedence in developing amino acid prodrugs • Improved pharmaceutical properties of already marketed compounds (e.g. valacyclovir, valganciclovir) and new chemical entities (e.g. brivanib alaninate, LY354740) • Proven to improve solubility, permeability, sustained release, targeting transporter, overcoming resistance. Introducing an amino acid, either a natural or its derivative, to a parent drug usually increases the water solubility by several orders of magnitude through an ionized carboxylate anion or ammonium cation. Consequently, there are several amino acid ester prodrugs that are investigated as water soluble derivatives for oral administration (Chan, 1998; Mulholland, 2001; Gingrich, 2003; Marathe, 2009). Amino acid esters (Bundgaard, 1984) amino acid amides (Pochopin, 1995; Bradshaw, 2002; Mittal, 2007; Rasheed, 2011) or other amino acid examples like amidoximes (Kotthaus, 2011) or ureas (Hemenway, 2010) have been investigated for parenteral use, albeit to a lesser extent. In proline, the side-chain links to the α-amino group, meaning it is the only