Indolidan
Indolidan is a small-molecule cardiotonic agent originally developed by Eli Lilly & Co. for the treatment of heart failure. Structurally classified as a 2-indolinone derivative, it acts primarily as a selective inhibitor of phosphodiesterase 3, thereby enhancing cardiac contractility by increasing intracellular cyclic AMP levels in cardiac myocytes. Indolidan has been investigated in clinical settings for its potential to improve cardiac output in patients with heart failure, but development has not advanced beyond early-phase clinical trials due to concerns about safety and overall efficacy.
Indolidan belongs to a class or family of chemicals that contain a pyridazinone ring. For example, it is structurally related to Levosimendan, pimobendan, siguazodan, zardaverine.
Synthesis
A Friedel–Crafts acylation of 3,3-dimethyloxindole with succinic anhydride afforded 5--4-oxobutyric acid, . Treatment with hydrazine afforded the pyridazinone ring closure, thus completing the synthesis of indolidan proper.An alternative way to create 3,3-dimethyloxindole starting material is from N'-phenylisobutyrohydrazide . Intramolecular ring closure is made to occur upon heating in calcium hydride.
A radiolabelled synthesis with carbon-14 and deuterium has also been described.