Sidechain structure-activity relationships of cyclobutane-based small molecule αvβ3 antagonists.

ABSTRACT: The integrin family of cell surface extracellular matrix binding proteins are key to several physiological processes involved in tissue development, as well as cancer proliferation and dissemination. They are therefore attractive targets for drug discovery with cancer and non-cancer applications. We have developed a new integrin antagonist chemotype incorporating a functionalised cyclobutane ring as the central scaffold in an arginine-glycine-aspartic acid mimetic structure. Here, we report the synthesis of cyclobutanecarboxylic acids and cyclobutylamines with tetrahydronaphthyridine and aminopyridine arginine mimetic sidechains and masked carboxylic acid aspartic acid mimetic sidechains of varying length. Effective αvβ3 antagonists and new aspartic acid mimetics were identified in cell-ba

SUBMITTER: Throup A 

PROVIDER: S-EPMC11393731 | biostudies-literature | 2024 Sep

REPOSITORIES: biostudies-literature