Indacrinone is a loop diuretic. It can be used in patients of gout with hypertension as an antihypertensive because it decreases reabsorption of uric acid,
Chirality and biological activity
Indacrinone is a
Chiral drugs, with one chiral center and hence exists as mirror-image twins. (R)-enantiomer, the
eutomer, is diuretic whereas the mirror-image version (S)-enantiomer counteracts side effect of the eutomer. Here both the enantiomers contribute to the overall desired effect in different ways.
As indicated earlier, the (R)- enantiomer is the pharmacologically active diuretic. Like most other diuretics, the (R)-isomer possesses an undesirable side-effect of retaining uric acid. But the (S)-enantiomer, the Eudysmic ratio, has the property of assisting uric acid secretion (uricosuric effect), and, therefore, antagonizing the undesirable side-effects of the eutomer (uric-acid retention).
Synthesis
The Friedel-Crafts acylation of 2,3-dichloroanisole 1984-59-4 (1) with phenylacetyl chloride 103-80-0 (2) gives 2,3-dichloro-4-phenylacetylanisole 59043-83-3 (3). 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). Acid catalyzed (H2SO4) intramolecular cyclization gives the indanone (PC10990444) (7). This is O-demethylated under acidic conditions to give 2-Phenyl-5-hydroxy-6,7-dichloro-1-indanone, PC12774089 (8). The phenol thus obtained is then alkylated on oxygen by iodoacetic acid 64-69-7 (9) affording PC20520826 (10). Alkylation with iodomethane 74-88-4 in the presence of sodium hydride completed the synthesis of indacrinone (11).
See also
