Synthesis of hydroxypyrone- and hydroxythiopyrone-based matrix metalloproteinase inhibitors: developing a structure-activity relationship.

ABSTRACT: The zinc(II)-dependent matrix metalloproteinases (MMPs) are associated with a variety of diseases. Development of inhibitors to modulate MMP activity has been an active area of investigation for therapeutic development. Hydroxypyrones and hydroxythiopyrones are alternative zinc-binding groups (ZBGs) that, when combined with peptidomimetic backbones, comprise a novel class of MMP inhibitors (MMPi). In this report, a series of hydroxypyrone- and hydroxythiopyrone-based MMPi with aryl backbones at the 2-, 5-, and 6-positions of the hydroxypyrone ring have been synthesized. Synthetic routes for developing inhibitors with substituents at two of these positions (so-called double-handed inhibitors) are also explored. The MMP inhibition profiles and structure-activity relationship of synthesized h

SUBMITTER: Yan YL 

PROVIDER: S-EPMC2833267 | biostudies-literature | 2009 Apr

REPOSITORIES: biostudies-literature