Alpha aminoacid ester-drug conjugates hydrolysable by carboxylesterase

摘要

Disclosed is a covalent conjugate of an alpha amino acid ester and an inhibitor of the activity of a target intracellular enzyme, wherein: the ester group of the conjugate is hydrolysable by one or more intracellular carboxylesterase enzymes to the corresponding acid; and the alpha amino acid ester is conjugated to the inhibitor at a position remote from the binding interface between the inhibitor and the target enzyme, whereby the amino acid conjugate which is the hydrolysis product of the alpha amino acid ester conjugate retains the intracellular binding activity of the present inhibitor with the target enzyme. Also disclosed is a method of increasing or prolonging the intracellular potency and/or residence time of an inhibitor of the activity of a target intracellular enzyme.