8 Unusual amino acids in Medicinal Chemistry
J. Med Chem. 2016, 59, 24, 10807-10836
The α-disubstitution can be combined with cyclisation of the side chains to form cyclic amino acids. This conformationally restricted mino acids are frequently used as core components of bioactive molecules.
For example, aminocyclobutane-1-carbxylic acid anchors the HCV NS5A polymerase inhibitor 1 (BILB1941), the first allosteric non-nucleoside inhibitor of its class to reach the clinic.
Clinical candidate 2 (AZD5363), an orally bioavailable, potent inhibitor of Akt kinases that inhibits tumor growth in a breast cancer xenograft model, is based around a piperidine-4-amino-4-carboxylic acid central residue. The same amino acid forms the core structure of opioid agonists 3 (Carfentanil) useful as anaesthetics