Patent Evaluation: Water soluble echinocandin C derivatives

Summary

Novelty: Cyclohexapeptide antibiotics, derivatives of echinocandin C, containing a homotyrosine radical in which the hydroxy group is substituted by acyl, phosphono- or sulpho- groups, are described. The charged group at neutral pH affords improved aqueous solubility.

Biology: The compounds are effective antifungal and antiprotozoal agents displaying potency against Aspergillus species, Fusarium species and Entamoeba histolytica. The preferred compounds A-1a and A-2a are useful for the prevention or treatment of Pneumocystis carinii infections in immunocompromised patients; they control Candida species at ≤30 μg/ml.

Chemistry: Full experimental details are included for seven derivatives and a further thirteen are tabulated. Compound A-1a is 1-[4,5-dihydroxy-N2-(10,12-dimethyl-1-oxotetradecyl)-ornithine]-2-serine-4-[3-hydroxy-4′-O-phosphorylhomotyrosine]-5-[3-hydroxyglutamine]-echinocandin C disodium salt and compound A-2a is 1-[4,5-dihydroxy-N2-(10,12-dimethyl-1-oxotetradecyl)-ornithine]-2-serine-4-[3-hydroxy-4′-O-phosphorylhomotyrosine-5-[3-hydroxyglutamine]-6-[3-hydroxyproline]-echinocandin C disodium salt.

Structure: