National Center for
3ZPT: Design and Synthesis of P1-P3 Macrocyclic Tertiary Alcohol Comprising HIV-1 Protease Inhibitors
J. Med. Chem. (2013) 56 p.8999-9007
To study P1-P3 macrocyclizations of previously reported tertiary-alcohol-comprising HIV-1 protease inhibitors (PIs), three new 14- and 15-member macrocyclic PIs were designed, synthesized by ring-closing metathesis, and evaluated alongside with 10 novel linear PIs. Cocrystallized complexes of the macrocyclic PIs and the HIV-1 protease are presented, analyzed, and discussed. The macrocyclic structures exhibited higher activities than the linear precursors with Ki and EC50 values down to 3.1 nM and 0.37 muM, respectively.