Design, synthesis and biological evaluation of 3-amino-3-phenylpropionamide derivatives as novel μ opioid receptor ligands

3-Amino-3-phenylpropionamide derivatives were produced as small molecule mimics of the cyclic octapeptide octreotide from readily available imine 1. The compounds exhibit high affinity for the μ opioid receptor. Scheme 1. Preparation of 3-amino-3-phenylpropionamide derivatives.[18] (a) TiCl4, CH2Cl2, rt., 10 h; 88%; (b) n-BuLi, R1NH2, THF, 0 °C; 15 min then add 3; 85–98% yield; (c) BBr3, CH2Cl2, −78 °C to rt; 80–95% yield; (d) RxCHO, NaBH(OAc)3, AcOH, CH2Cl2, rt; 10 h; 65–95% yield.