Small molecule therapeutic compounds targeting thioesterase deficiency disorders and methods of using the same

摘要

The invention provides methods of inhibiting the development or progression of a thioesterase deficiency disorder in a mammal by the administration of a compound that functionally mimics the enzymatic activity of all thioesterases in mammals. Such thioesterase deficiency disorders include cancers and adult- or infant-neuronal ceroid lipofuscinoses (NCLs). The invention also provides small molecule mimics of thioesterases useful in the methods of the invention and pharmaceutical compositions containing the therapeutically effective compounds and methods of using the same.

主权项

1. A method of preventing, treating or ameliorating a thioesterase deficiency disorder disease selected from neuronal ceroid lipofuscinosis (NCL), infantile NCL, and juvenile NCL, comprising administering to a mammal in need of such treatment, a therapeutically effective amount of a compound that functionally mimics a thioesterase enzymatic activity selected from the group consisting of: N-t-butyl hydroxylamine (NtBUHA), N-Methylhydroxylamine, N,N-Dimethylhydroxylamine, N,N-Diethylhydroxylamine, N-Cyclohexylhydroxylamine, N,O-Bis(trimethylsilyl)hydroxylamine, N-Benzylhydroxylamine, N-Benzyloxycarbonyl), N,O-Di-Boc-hydroxylamine, N-Benzoyl-N-phenyl hydroxylamine, N,N-Dibenzylhydroxylamine, N-tert-Butyl-O-[1-[4-(chloromethyl)phenyl]ethyl]-N-(2-methyl-1-phenylpropyl)hydroxylamine, and pharmaceutically-acceptable salts thereof.