Design and synthesis of novel macrocyclic 2-amino-6-arylpyrimidine Hsp90 inhibitors

Novel macrocyclic Hsp90 inhibitors were identified through structure-based drug design. Among them, CH5164840 showed high binding affinity for Hsp90, potent anti-proliferative activity, high oral bioavailability in mice and potent antitumor efficacy in a human cancer xenograft model.