Suritozole Explained

Suritozole (MDL 26,479) is an investigational cognition enhancer. It acts as a partial inverse agonist at the benzodiazepine receptor site on the GABA_A ion channel complex, but does not have either anxiogenic or convulsant effects, unlike other BZD inverse agonists such as DMCM.^[1] It was investigated for the treatment of depression and Alzheimer's disease,^[2] but clinical development seems to have been discontinued.

Synthesis

The reaction between monomethylhydrazine [60-34-4] (1) and methyl isothiocyanate (Trapex) [556-61-6] (2) gave 2,4-dimethylthiosemicarbazide [6621-75-6] (3). Amide formation with 3-fluorobenzoyl chloride [1711-07-5] (4) yielded 1-(3-fluorobenzoyl)-2,4-dimethylthiosemicarbazide [110623-52-4] (5). Cyclization to Suritozole (6).

See also

• GABA_A receptor negative allosteric modulator
• GABA_A receptor § Ligands

Notes and References

1. Miller JA, Dudley MW, Kehne JH, Sorensen SM, Kane JM . MDL 26,479: a potential cognition enhancer with benzodiazepine inverse agonist-like properties . British Journal of Pharmacology . 107 . 1 . 78–86 . September 1992 . 1330168 . 1907590 . 10.1111/j.1476-5381.1992.tb14466.x .
2. Robbins DK, Hutcheson SJ, Miller TD, Green VI, Bhargava VO, Weir SJ . Pharmacokinetics of MDL 26479, a novel benzodiazepine inverse agonist, in normal volunteers . Biopharmaceutics & Drug Disposition . 18 . 4 . 325–334 . May 1997 . 9158880 . 10.1002/(SICI)1099-081X(199705)18:4<325::AID-BDD21>3.0.CO;2-1 .