Amide derivatives of partricin A with potent antifungal activity

A series of partricin A amides were synthesized using the active ester method by reaction with several amines on the carboxy group and then with some acids on the mycosamine group of partricin A. Most of the derivatives are more potent antifungals than the known reference standards, including amphotericin B, and a few are also less toxic and less hemolytic. Amides substituted with basic groups may give hydrosoluble salts, useful for injectable formulations, and two derivatives were selected for further development, namely, partricin A 2-dimethylaminoethyl amide (10, SPA-S-710) and N-dimethylaminoacetyl-partricin A 2-dimethylaminoethyl amide (22, SPA-S-752).