Acetylenic linkers in lead compounds: a study of the stability of the propargyl-linked antifolates.

ABSTRACT: Propargyl-linked antifolates that target dihydrofolate reductase are potent inhibitors of several species of pathogenic bacteria and fungi. This novel class of antifolates possesses a relatively uncommon acetylenic linker designed to span a narrow passage in the enzyme active site and join two larger functional domains. Because the use of alkyne functionality in drug molecules is limited, it was important to evaluate some key physicochemical properties of these molecules and specifically to assess the overall stability of the acetylene. Herein, we report studies on four compounds from our lead series that vary specifically in the environment of the alkyne. We show that the compounds are soluble, chemically stable in water, as well as simulated gastric and intestinal fluids with half-lives

SUBMITTER: Zhou W 

PROVIDER: S-EPMC3463820 | biostudies-literature | 2012 Oct

REPOSITORIES: biostudies-literature