Lipopeptide antifungal agents: Amine conjugates of the semi-synthetic pneumocandins L-731,373 and L-733,560
Zambias, R., A.; James, C.; Abruzzo, G., K.; Bartizal, K., F.; Hajdu, R.; Thompson, R.; Nollstadt, K., H.; Marrinan, J.; Balkovec, J., M.
Bioorganic and Medicinal Chemistry Letters 7(15): 2021-2026
ISSN/ISBN: 0960-894X DOI: 10.1016/s0960-894x(97)00359-4
Amine conjugates of the semi-synthetic 1,3-beta-(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.