Synthesis and Biochemical Evaluation of Lid-Open D-Amino Acid Oxidase Inhibitors.

ABSTRACT: Most of the known inhibitors of D-amino acid oxidase (DAAO) are small polar molecules recognized by the active site of the enzyme. More recently a new class of DAAO inhibitors has been disclosed that interacts with loop 218-224 at the top of the binding pocket. These compounds have a significantly larger size and more beneficial physicochemical properties than most reported DAAO inhibitors, however, their structure-activity relationship is poorly explored. Here we report the synthesis and evaluation of this type of DAAO inhibitors that open the lid over the active site of DAAO. In order to collect relevant SAR data we varied two distinct parts of the inhibitors. A systematic variation of the pendant aromatic substituents according to the Topliss scheme resulted in DAAO inhibitors with low

SUBMITTER: Szilagyi B 

PROVIDER: S-EPMC6358909 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature