Lipopeptide antifungal agents: Amine conjugates of the semi-synthetic pneumocandins L-731,373 and L-733,560

Abstract Amine conjugates of the semi-synthetic 1,3-β-(D)-glucan synthesis inhibitors L-731,373 ( 3 ) and L-733,560 ( 4 ) were prepared and evaluated for in vitro and in vivo antifungal activity. Tricationic analogs were more potent than the dicationic which were more potent than the monocationic. The L-ornithine conjugate of 4 possessed excellent pharmacokinetic parameters but lacked sufficient antifungal spectrum for development.