Pagoclone

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Pagoclone
Clinical data
ATC code
  • none
Identifiers
  • 2-(7-chloro-1,8-naphthyridin-2-yl)-3-(5-methyl-2-oxohexyl)isoindolin-1-one
JSmol)
  • Clc1nc2nc(ccc2cc1)N4C(=O)c3ccccc3C4CC(=O)CCC(C)C
  • InChI=1S/C23H22ClN3O2/c1-14(2)7-10-16(28)13-19-17-5-3-4-6-18(17)23(29)27(19)21-12-9-15-8-11-20(24)25-22(15)26-21/h3-6,8-9,11-12,14,19H,7,10,13H2,1-2H3 checkY
  • Key:HIUPRQPBWVEQJJ-UHFFFAOYSA-N checkY
 ☒NcheckY (what is this?)  (verify)

Pagoclone is an

cyclopyrrolone family, related to better-known drugs such as the sleeping medication zopiclone. It was synthesized by a French team working for Rhone-Poulenc & Rorer S.A.[1] Pagoclone belongs to the class of nonbenzodiazepines, which have similar effects to the older benzodiazepine group, but with quite different chemical structures
. It was never commercialised.

It binds with roughly equivalent high affinity (0.7–9.1 nM) to the benzodiazepine

amnestic actions at low doses (0.3mg to 1.2mg per day).[4]

The pharmacologist David Nutt has suggested pagoclone as a possible base from which to make a better social drug, as it produces the positive effects of alcohol, such as relaxation and sociability, but without also causing the negative effects like aggression, amnesia, nausea, loss of coordination and liver damage. Its effect can be quickly reversed by the action of flumazenil, which is already used as an antidote to benzodiazepine overdose.[5] Nutt has published studies[6] praising the potential of pagoclone which were financed by Indevus which was seeking funding for a possible production of the compound. The long-term safety of pagoclone has not been assessed. The abuse potential of pagoclone has been assessed as being similar to, or slightly less than that of diazepam and it would also be expected to be somewhat safer due to its relatively weaker sedative effects,[7] but development of pagoclone as a commercial drug would still be unlikely due to concerns about abuse.[citation needed]

Pagoclone was trialed as a drug to improve a

stammerer's speech fluency,[8]
but research for this application was discontinued following disappointing results in Phase II clinical trials.

Synthesis

Pagoclone and pazinaclone both contain an isoindolone structural motif

Pagoclone synthesis: U.S. patent 4,960,779

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 give the corresponding alcohol. Reaction with the carbanion from Ethyl 5-methyl-3-oxohexanoate leads to the product from the displacement of the hydroxyl group; 'this too may proceed via the acrylate obtained from aldol reaction of the ring opened imidal'.

See also

References

  1. ^ US 5498716, David-Comte MT, Roussel G, "2-Amino naphthyridine derivative, its preparation and its use", issued 12 March 1996, assigned to Rhone Poulenc Rorer SA. 
  2. S2CID 12090552
    .
  3. S2CID 22793644
    .
  4. PMID 12871032
    .
  5. S2CID 44290147
    .
  6. S2CID 35569523
    .
  7. S2CID 33351598
    .
  8. S2CID 29633149
    .
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