Indacrinone

It can be used in patients of gout with hypertension as an antihypertensive because it decreases reabsorption of uric acid,[1] while other diuretics increase it.

But the (S)-enantiomer, the distomer, has the property of assisting uric acid secretion (uricosuric effect), and, therefore, antagonizing the undesirable side-effects of the eutomer (uric-acid retention).

A variation of the Mannich reaction is performed employing tetramethyldiaminomethane [51-80-9] (this is an aminal of dimethylamine and formaldehyde).

The intermediate reaction product (5), which is not isolated, would undergo a β-Hydride elimination with concomitant loss of dimethylamine and formation of the corresponding enone, 2,3-Dichloro-4-(2-phenylacryloyl)anisole (PC10924810) (6).

Alkylation with iodomethane [74-88-4] in the presence of sodium hydride completed the synthesis of indacrinone (11).

Indacrinone enantiomeric pair exhibiting therapeutic advantage
Indacrinone - Chiral twins
ChemDrug Synthesis: [ 5 ] [ 6 ] Patent: [ 7 ] Use patent: [ 8 ] Enantioselective method: [ 9 ]