Lirequinil

Lirequinil (Ro41-3696) is a nonbenzodiazepine hypnotic drug which binds to benzodiazepine sites on the GABAA receptor. In human clinical trials, lirequinil was found to have similar efficacy to zolpidem, with less side effects such as clumsiness and memory impairment. However it was also much slower acting than zolpidem, with peak plasma concentrations not reached until 2.5 hours after oral administration, and its O-desethyl metabolite Ro41-3290 is also active with a half-life of 8 hours.[1][2][3][4] This meant that while effective as a hypnotic, lirequinil failed to prove superior to zolpidem due to producing more next-day sedation, and it has not been adopted for clinical use. It was developed by a team at Hoffmann-La Roche in the 1990s.[5]

Active metabolite Ro41-3290
Lirequinil
Clinical data
ATC code
  • none
Identifiers
IUPAC name
  • 10-chloro-1-[(3S)-3-ethoxypyrrolidine-1-carbonyl]-3-phenyl-6,7-dihydrobenzo[a]quinolizin-4-one
CAS Number
PubChem CID
ChemSpider
UNII
CompTox Dashboard (EPA)
Chemical and physical data
FormulaC26H25ClN2O3
Molar mass448.95 g·mol−1
3D model (JSmol)
SMILES
  • CCO[C@H]1CCN(C1)C(=O)C2=C3C4=C(CCN3C(=O)C(=C2)C5=CC=CC=C5)C=CC(=C4)Cl
InChI
  • InChI=1S/C26H25ClN2O3/c1-2-32-20-11-12-28(16-20)25(30)23-15-22(17-6-4-3-5-7-17)26(31)29-13-10-18-8-9-19(27)14-21(18)24(23)29/h3-9,14-15,20H,2,10-13,16H2,1H3/t20-/m0/s1 N
  • Key:CBSWRAUYCIIUEI-FQEVSTJZSA-N N
 NY (what is this?)  (verify)

References
  1. Dingemanse J, Bury M, Roncari G, Zell M, Gieschke R, Gaillard AW, Odink J, van Brummelen P (August 1995). "Pharmacokinetics and pharmacodynamics of Ro 41-3696, a novel nonbenzodiazepine hypnotic". Journal of Clinical Pharmacology. 35 (8): 821–9. doi:10.1002/j.1552-4604.1995.tb04126.x. PMID 8522640. S2CID 20456430.
  2. Dingemanse J, Bury M, Bock J, Joubert P (November 1995). "Comparative pharmacodynamics of Ro 41-3696, a new hypnotic, and zolpidem after night-time administration to healthy subjects". Psychopharmacology. 122 (2): 169–74. doi:10.1007/BF02246091. PMID 8848532. S2CID 11960902.
  3. Dingemanse J, Bury M, Hussain Y, van Giersbergen P (December 2000). "Comparative tolerability, pharmacodynamics, and pharmacokinetics of a metabolite of a quinolizinone hypnotic and zolpidem in healthy subjects". Drug Metabolism and Disposition. 28 (12): 1411–6. PMID 11095577.
  4. Dingemanse J, Pedrazzetti E, van Giersbergen PL (2001). "Multiple-dose tolerability, pharmacodynamics, and pharmacokinetics of the quinolizinone hypnotic Ro 41-3696 in elderly subjects". Clinical Neuropharmacology. 24 (2): 82–90. doi:10.1097/00002826-200103000-00003. PMID 11307042. S2CID 21588500.
  5. US Patent 5561233 Process for the preparation of an intermediate of a benzo[a]quinolizinone derivative
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