Pazinaclone Explained

Pazinaclone (DN-2327) is a sedative and anxiolytic drug in the cyclopyrrolone family of drugs. Some other cyclopyrrolone drugs include zopiclone and eszopiclone.

Pazinaclone has a very similar pharmacological profile to the benzodiazepines including sedative and anxiolytic properties, but with less amnestic effects,[1] and at low doses it is a relatively selective anxiolytic, with sedative effects only appearing at higher doses.[2]

Pazinaclone produces its sedative and anxiolytic effects by acting as a partial agonist at GABAA benzodiazepine receptors, although pazinaclone is more subtype-selective than most benzodiazepines.[3]

Synthesis

Reaction of 2-amino-7-chloro-1,8-naphthyridine with phthalic anhydride leads to the corresponding phthalimide. Selective reduction of one of the imide carbonyl groups in essence converts that to an aldehyde. Condensation with tert-butyl(triphenylphosphoranylidene)acetate gives the Wittig product.

The carboxylic acid is then treated with diethyl cyanophosphonate to convert that to an activated acid cyanide; reaction with 1,4-dioxa-8-azaspiro[4.5]decane results in formation of the corresponding amide, pazinaclone.

See also

Notes and References

  1. Wada T, Fukuda N . Effect of a new anxiolytic, DN-2327, on learning and memory in rats . Pharmacology, Biochemistry, and Behavior . 41 . 3 . 573–9 . March 1992 . 1350101 . 10.1016/0091-3057(92)90375-p . 20581568 .
  2. Suzuki M, Uchiumi M, Murasaki M . A comparative study of the psychological effects of DN-2327, a partial benzodiazepine agonist, and alprazolam . Psychopharmacology . 121 . 4 . 442–50 . October 1995 . 8619007 . 10.1007/BF02246492 . 35222663 .
  3. Atack JR . The benzodiazepine binding site of GABA(A) receptors as a target for the development of novel anxiolytics . Expert Opinion on Investigational Drugs . 14 . 5 . 601–18 . May 2005 . 15926867 . 10.1517/13543784.14.5.601 . 22793644 .