Lirequinil

Chemical compound

none

Identifiers

IUPAC name

10-chloro-1-[(3S)-3-ethoxypyrrolidine-1-carbonyl]-3-phenyl-6,7-dihydrobenzo[a]quinolizin-4-one

CAS Number

143943-73-1^Y

PubChem CID

3045375

ChemSpider

2308119^N

UNII

2VUW1087AD

ChEMBL

ChEMBL2105118

CompTox Dashboard (EPA)

DTXSID80162579

Chemical and physical dataFormulaC₂₆H₂₅ClN₂O₃Molar mass448.95 g·mol⁻¹3D model (JSmol)

Interactive image

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)

Lirequinil (Ro41-3696) is a nonbenzodiazepine hypnotic drug which binds to benzodiazepine sites on the GABA_A 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]

References

^ 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.
^ 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.
^ 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.
^ 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.
^ US Patent 5561233 Process for the preparation of an intermediate of a benzo[a]quinolizinone derivative

Hypnotics/sedatives (N05C)

GABA_A

Alcohols	2M2B Chloralodol Ethanol (alcohol) Diethylpropanediol Ethchlorvynol Methylpentynol Trichloroethanol
Barbiturates	Allobarbital Amobarbital Aprobarbital Barbital Butabarbital Butobarbital Cyclobarbital Ethallobarbital Heptabarb Hexobarbital Mephobarbital Methohexital Narcobarbital Pentobarbital Phenallymal Phenobarbital Propylbarbital Proxibarbal Reposal Secobarbital Talbutal Thiamylal Thiopental Thiotetrabarbital Vinbarbital Vinylbital
Benzodiazepines	Brotizolam Cinolazepam Climazolam Clonazolam Doxefazepam Estazolam Flubromazolam Flunitrazolam Flunitrazepam Flurazepam Flutoprazepam Lorazepam Loprazolam Lormetazepam Midazolam Nimetazepam Nitemazepam Nitrazepam Nitrazolam Quazepam Temazepam Triazolam
Carbamates	Carisoprodol Emylcamate Ethinamate Hexapropymate Meprobamate Methocarbamol Phenprobamate Procymate Tybamate
Imidazoles	Etomidate Metomidate Propoxate
Monoureides	Acecarbromal Apronal (apronalide) Bromisoval Capuride Carbromal Ectylurea
Neuroactive steroids	Acebrochol Allopregnanolone Alphadolone Alphaxolone Eltanolone Hydroxydione Minaxolone Progesterone
Nonbenzodiazepines	Eszopiclone Indiplon Lirequinil Necopidem Pazinaclone Saripidem Suproclone Suriclone Zaleplon Zolpidem Zopiclone
Phenols	Propofol
Piperidinediones	Glutethimide Methyprylon Pyrithyldione Piperidione
Quinazolinones	Afloqualone Cloroqualone Diproqualone Etaqualone Mebroqualone Mecloqualone Methaqualone Methylmethaqualone Nitromethaqualone SL-164
Others	Acetophenone Acetylglycinamide chloral hydrate Bromide compounds Lithium bromide Potassium bromide Sodium bromide Centalun Chloral betaine Chloral hydrate Chloralose Clomethiazole Dichloralphenazone Gaboxadol Kavalactones Loreclezole Paraldehyde Petrichloral Sulfonylalkanes Sulfonmethane (sulfonal) Tetronal Trional Triclofos Sesquiterpene Isovaleramide Isovaleric acid Valerenic acid

GABA_B

H₁

Antihistamines	Captodiame Cyproheptadine Diphenhydramine Doxylamine Hydroxyzine Methapyrilene Perlapine Pheniramine Promethazine Propiomazine
Antidepressants	Serotonin antagonists and reuptake inhibitors Etoperidone Nefazodone Trazodone Tricyclic antidepressants Amitriptyline Doxepin Trimipramine, etc. Tetracyclic antidepressants Mianserin Mirtazapine, etc.
Antipsychotics	Typical antipsychotics Chlorpromazine Thioridazine, etc. Atypical antipsychotics Olanzapine Quetiapine Risperidone, etc.

α₂-Adrenergic

5-HT_2A

Antidepressants	Trazodone Tricyclic antidepressants Amitriptyline Doxepin Trimipramine, etc. Tetracyclic antidepressants Mianserin Mirtazapine, etc.
Antipsychotics	Typical antipsychotics Chlorpromazine Thioridazine, etc. Atypical antipsychotics Olanzapine Quetiapine Risperidone, etc.
Others	Niaprazine

Melatonin

Orexin

α₂δ VDCC

Others

v t e GABA_A receptor positive modulators
Alcohols	Brometone Butanol Chloralodol Chlorobutanol (cloretone) Ethanol (alcohol) (alcoholic drink) Ethchlorvynol Isobutanol Isopropanol Menthol Methanol Methylpentynol Pentanol Petrichloral Propanol tert-Butanol (2M2P) tert-Pentanol (2M2B) Tribromoethanol Trichloroethanol Triclofos Trifluoroethanol
Barbiturates	(-)-DMBB Allobarbital Alphenal Amobarbital Aprobarbital Barbexaclone Barbital Benzobarbital Benzylbutylbarbiturate Brallobarbital Brophebarbital Butabarbital/Secbutabarbital Butalbital Buthalital Butobarbital Butallylonal Carbubarb Crotylbarbital Cyclobarbital Cyclopentobarbital Difebarbamate Enallylpropymal Ethallobarbital Eterobarb Febarbamate Heptabarb Heptobarbital Hexethal Hexobarbital Metharbital Methitural Methohexital Methylphenobarbital Narcobarbital Nealbarbital Pentobarbital Phenallymal Phenobarbital Phetharbital Primidone Probarbital Propallylonal Propylbarbital Proxibarbital Reposal Secobarbital Sigmodal Spirobarbital Talbutal Tetrabamate Tetrabarbital Thialbarbital Thiamylal Thiobarbital Thiobutabarbital Thiopental Thiotetrabarbital Valofane Vinbarbital Vinylbital
Benzodiazepines	2-Oxoquazepam 3-Hydroxyphenazepam Adinazolam Alprazolam Arfendazam Avizafone Bentazepam Bretazenil Bromazepam Bromazolam Brotizolam Camazepam Carburazepam Chlordiazepoxide Ciclotizolam Cinazepam Cinolazepam Clazolam Climazolam Clobazam Clonazepam Clonazolam Cloniprazepam Clorazepate Clotiazepam Cloxazolam CP-1414S Cyprazepam Delorazepam Demoxepam Diazepam Diclazepam Doxefazepam Elfazepam Estazolam Ethyl carfluzepate Ethyl dirazepate Ethyl loflazepate Etizolam EVT-201 FG-8205 Fletazepam Flubromazepam Flubromazolam Fludiazepam Flunitrazepam Flunitrazolam Flurazepam Flutazolam Flutemazepam Flutoprazepam Fosazepam Gidazepam Halazepam Haloxazolam Iclazepam Imidazenil Irazepine Ketazolam Lofendazam Lopirazepam Loprazolam Lorazepam Lormetazepam Meclonazepam Medazepam Menitrazepam Metaclazepam Mexazolam Midazolam Motrazepam N-Desalkylflurazepam Nifoxipam Nimetazepam Nitrazepam Nitrazepate Nitrazolam Nordazepam Nortetrazepam Oxazepam Oxazolam Phenazepam Pinazepam Pivoxazepam Prazepam Premazepam Proflazepam Pyrazolam QH-II-66 Quazepam Reclazepam Remimazolam Rilmazafone Ripazepam Ro48-6791 Ro48-8684 SH-053-R-CH3-2′F Sulazepam Temazepam Tetrazepam Tolufazepam Triazolam Triflubazam Triflunordazepam (Ro5-2904) Tuclazepam Uldazepam Zapizolam Zolazepam Zomebazam
Carbamates	Carisbamate Carisoprodol Clocental Cyclarbamate Difebarbamate Emylcamate Ethinamate Febarbamate Felbamate Hexapropymate Hydroxyphenamate Lorbamate Mebutamate Meprobamate Nisobamate Pentabamate Phenprobamate Procymate Styramate Tetrabamate Tybamate
Flavonoids	6-Methylapigenin Ampelopsin (dihydromyricetin) Apigenin Baicalein Baicalin Catechin EGC EGCG Hispidulin Linarin Luteolin Rc-OMe Skullcap constituents (e.g., baicalin) Wogonin
Imidazoles	Etomidate Metomidate Propoxate
Kava constituents	10-Methoxyyangonin 11-Methoxyyangonin 11-Hydroxyyangonin Desmethoxyyangonin 11-Methoxy-12-hydroxydehydrokavain 7,8-Dihydroyangonin Kavain 5-Hydroxykavain 5,6-Dihydroyangonin 7,8-Dihydrokavain 5,6,7,8-Tetrahydroyangonin 5,6-Dehydromethysticin Methysticin 7,8-Dihydromethysticin Yangonin
Monoureides	Acecarbromal Apronal (apronalide) Bromisoval Carbromal Capuride Ectylurea
Neuroactive steroids	Acebrochol Allopregnanolone (brexanolone) Alfadolone Alfaxalone 3α-Androstanediol Androstenol Androsterone Certain anabolic-androgenic steroids Cholesterol DHDOC 3α-DHP 5α-DHP 5β-DHP DHT Etiocholanolone Ganaxolone Hydroxydione Minaxolone ORG-20599 ORG-21465 P1-185 Posovolone Pregnanolone (eltanolone) Progesterone Renanolone SAGE-105 SAGE-324 SAGE-516 SAGE-689 SAGE-872 Testosterone THDOC Zuranolone
Nonbenzodiazepines	Cyclopyrrolones: Eszopiclone Pagoclone Pazinaclone Suproclone Suriclone Zopiclone Imidazopyridines: Alpidem DS-1 Necopidem Saripidem Zolpidem Pyrazolopyrimidines: Divaplon Fasiplon Indiplon Lorediplon Ocinaplon Panadiplon Taniplon Zaleplon Others: Adipiplon CGS-8216 CGS-9896 CGS-13767 CGS-20625 CL-218,872 CP-615,003 CTP-354 ELB-139 GBLD-345 Imepitoin JM-1232 L-838,417 Lirequinil (Ro41-3696) NS-2664 NS-2710 NS-11394 Pipequaline ROD-188 RWJ-51204 SB-205,384 SX-3228 TGSC01AA TP-003 TPA-023 TP-13 U-89843A U-90042 Viqualine Y-23684
Phenols	Fospropofol Propofol Thymol
Piperidinediones	Glutethimide Methyprylon Piperidione Pyrithyldione
Pyrazolopyridines	Cartazolate Etazolate ICI-190,622 Tracazolate
Quinazolinones	Afloqualone Cloroqualone Diproqualone Etaqualone Mebroqualone Mecloqualone Methaqualone Methylmethaqualone Nitromethaqualone SL-164
Volatiles/gases	Acetone Acetophenone Acetylglycinamide chloral hydrate Aliflurane Benzene Butane Butylene Centalun Chloral Chloral betaine Chloral hydrate Chloroform Cryofluorane Desflurane Dichloralphenazone Dichloromethane Diethyl ether Enflurane Ethyl chloride Ethylene Fluroxene Gasoline Halopropane Halothane Isoflurane Kerosine Methoxyflurane Methoxypropane Nitric oxide Nitrogen Nitrous oxide Norflurane Paraldehyde Propane Propylene Roflurane Sevoflurane Synthane Teflurane Toluene Trichloroethane (methyl chloroform) Trichloroethylene Vinyl ether
Others/unsorted	3-Hydroxybutanal α-EMTBL AA-29504 Alogabat Avermectins (e.g., ivermectin) Bromide compounds (e.g., lithium bromide, potassium bromide, sodium bromide) Carbamazepine Chloralose Chlormezanone Clomethiazole Darigabat DEABL Deuterated etifoxine Dihydroergolines (e.g., dihydroergocryptine, dihydroergosine, dihydroergotamine, ergoloid (dihydroergotoxine)) DS2 Efavirenz Etazepine Etifoxine Fenamates (e.g., flufenamic acid, mefenamic acid, niflumic acid, tolfenamic acid) Fluoxetine Flupirtine Hopantenic acid KRM-II-81 Lanthanum Lavender oil Lignans (e.g., 4-O-methylhonokiol, honokiol, magnolol, obovatol) Loreclezole Menthyl isovalerate (validolum) Monastrol Niacin Niacinamide Org 25,435 Phenytoin Propanidid Retigabine (ezogabine) Safranal Seproxetine Stiripentol Sulfonylalkanes (e.g., sulfonmethane (sulfonal), tetronal, trional) Terpenoids (e.g., borneol) Topiramate Valerian constituents (e.g., isovaleric acid, isovaleramide, valerenic acid, valerenol) Unsorted benzodiazepine site positive modulators: α-Pinene MRK-409 (MK-0343) TCS-1105 TCS-1205
See also: Receptor/signaling modulators • GABA receptor modulators • GABA metabolism/transport modulators