Seryl-lysyl-based peptide and peptidomimetic inhibitors of N- myristoyl transferase as anti-infective agents

摘要

Seryl-lysyl-based peptide and peptidomimetic compounds are described as inhibitors of the enzyme N-myristoyl transferase to provide selective control of the fungal organism Candida albicans. Peptidomimetic compounds of particular interest are those of the formula: ##STR1## wherein R.sup.1 is selected form aminoalkyl, p- aminoalkylphenylalkyl, imidazolylalkylphenylalkyl, 2- alkylimidazolylalkylphenylalkyl, benzimidazolylalkylphenylalkyl and 2- alkylbenzimidazolylalkylphenylalkyl; wherein R.sup.2 is selected from hydrido, alkyl, cycloalkyl, akenyl, alkynyl, haloalkyl, benzyl, alkylphenylalkyl, alkoxyphenylalkyl, halophenylalkyl, phenethyl, cycloalkylalkyl, halocycloalkylalkyl, alkylcycloalkylalkyl, alkoxycycloalkylalkyl and naphthylalkyl; wherein Y is selected from carboxylic acid, hydroxamic acid, phosphonic acid and tetrazolyl; or a pharmaceutically-acceptable salt, amide or ester thereof. Compounds of the formula are species-specific inhibitors of C. albicans with little effect on human NMT enzyme and thus would be useful in treating C. albicans fungal infections in humans.