ZK-93423 - Misplaced Pages

Chemical compound Pharmaceutical compound

ZK-93423
Clinical data

ATC code	none
Legal status
Legal status	In general: legal
Identifiers
IUPAC name ethyl 4-(methoxymethyl)-6-(phenylmethoxy) -9H-pyridoindole-3-carboxylate
CAS Number	83910-44-5
PubChem CID	121926
IUPHAR/BPS	4346
ChemSpider	108771
UNII	B6PWX5B47Q
ChEBI	CHEBI:92593
ChEMBL	ChEMBL1518572
CompTox Dashboard (EPA)	DTXSID101004052
Chemical and physical data
Formula	C₂₃H₂₂N₂O₄
Molar mass	390.439 g·mol
3D model (JSmol)	Interactive image
SMILES c3ccccc3COc(cc4)cc2c4c(cnc1C(=O)OCC)c2c1COC
InChI InChI=1S/C23H22N2O4/c1-3-28-23(26)22-18(14-27-2)21-17-11-16(29-13-15-7-5-4-6-8-15)9-10-19(17)25-20(21)12-24-22/h4-12,25H,3,13-14H2,1-2H3 Key:ALBKMJDFBZVHAK-UHFFFAOYSA-N
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ZK-93423 is an anxiolytic drug from the β-Carboline family, closely related to abecarnil. It is a nonbenzodiazepine GABA_A agonist which is not subtype selective and stimulates α₁, α₂, α₃, and α₅-subunit containing GABA_A receptors equally. It has anticonvulsant, muscle relaxant and appetite stimulating properties comparable to benzodiazepine drugs. ZK-93423 has also been used as a base to develop new and improved beta-carboline derivatives and help map the binding site of the GABA_A receptor.

References

Zhang H, Larock RC (December 2002). "Synthesis of beta- and gamma-carbolines by the palladium-catalyzed iminoannulation of alkynes". The Journal of Organic Chemistry. 67 (26): 9318–30. doi:10.1021/jo026317u. PMID 12492334.
Stephens DN, Shearman GT, Kehr W (1984). "Discriminative stimulus properties of beta-carbolines characterized as agonists and inverse agonists at central benzodiazepine receptors". Psychopharmacology. 83 (3): 233–9. doi:10.1007/BF00464787. PMID 6089245. S2CID 1479932.
Klockgether T, Pardowitz I, Schwarz M, Sontag KH, Turski L (October 1985). "Evaluation of the muscle relaxant properties of a novel beta-carboline, ZK 93423 in rats and cats". British Journal of Pharmacology. 86 (2): 357–66. doi:10.1111/j.1476-5381.1985.tb08904.x. PMC 1916712. PMID 3931731.
Cooper SJ (January 1986). "Hyperphagic and anorectic effects of beta-carbolines in a palatable food consumption test: comparisons with triazolam and quazepam". European Journal of Pharmacology. 120 (3): 257–65. doi:10.1016/0014-2999(86)90466-8. PMID 3753939.
File SE, Baldwin HA (September 1987). "Effects of beta-carbolines in animal models of anxiety". Brain Research Bulletin. 19 (3): 293–9. doi:10.1016/0361-9230(87)90097-9. PMID 3315125. S2CID 54428766.
Löscher W, Hönack D, Hashem A (November 1987). "Anticonvulsant efficacy of clonazepam and the beta-carboline ZK 93423 during chronic treatment in amygdala-kindled rats". European Journal of Pharmacology. 143 (3): 403–14. doi:10.1016/0014-2999(87)90464-X. PMID 3691663.
Dodd RH, Ouannès C, Potier MC, Prado de Carvalho L, Rossier J, Potier P (July 1987). "Synthesis of beta-carboline-benzodiazepine hybrid molecules: use of the known structural requirements for benzodiazepine and beta-carboline binding in designing a novel, high-affinity ligand for the benzodiazepine receptor". Journal of Medicinal Chemistry. 30 (7): 1248–54. doi:10.1021/jm00390a023. PMID 3037081.
Hollinshead SP, Trudell ML, Skolnick P, Cook JM (March 1990). "Structural requirements for agonist actions at the benzodiazepine receptor: studies with analogues of 6-(benzyloxy)-4-(methoxymethyl)-beta-carboline-3-carboxylic acid ethyl ester". Journal of Medicinal Chemistry. 33 (3): 1062–9. doi:10.1021/jm00165a028. PMID 1968513.
Diaz-Arauzo H, Evoniuk GE, Skolnick P, Cook JM (May 1991). "The agonist pharmacophore of the benzodiazepine receptor. Synthesis of a selective anticonvulsant/anxiolytic". Journal of Medicinal Chemistry. 34 (5): 1754–6. doi:10.1021/jm00109a035. PMID 1674542.
Sharma RC, Ojha TN, Tiwari S, Singh P (1992). "Quantitative structure-activity relationship study of some benzodiazepine-receptor ligands having inverse agonist/antagonist and agonist actions". Drug Design and Discovery. 9 (2): 135–43. PMID 1338366.
Cox ED, Diaz-Arauzo H, Huang Q, Reddy MS, Ma C, Harris B, McKernan R, Skolnick P, Cook JM (July 1998). "Synthesis and evaluation of analogues of the partial agonist 6-(propyloxy)-4-(methoxymethyl)-beta-carboline-3-carboxylic acid ethyl ester (6-PBC) and the full agonist 6-(benzyloxy)-4-(methoxymethyl)-beta-carboline-3-carboxylic acid ethyl ester (Zk 93423) at wild type and recombinant GABAA receptors". Journal of Medicinal Chemistry. 41 (14): 2537–52. doi:10.1021/jm970460b. PMID 9651158.
Ferretti V, Gilli P, Borea PA (August 2004). "Structural features controlling the binding of beta-carbolines to the benzodiazepine receptor". Acta Crystallographica B. 60 (Pt 4): 481–9. doi:10.1107/S0108768104013564. PMID 15258407.

v t e Anxiolytics (N05B)
5-HT_1ARTooltip 5-HT1A receptor agonists	Buspirone Gepirone Tandospirone
GABA_ARTooltip GABAA receptor PAMsTooltip positive allosteric modulators	Benzodiazepines: Adinazolam Alprazolam Bromazepam Camazepam Chlordiazepoxide Clobazam Clonazepam Clorazepate Clotiazepam Cloxazolam Diazepam Ethyl loflazepate Etizolam Fludiazepam Halazepam Ketazolam Lorazepam Medazepam Nordazepam Oxazepam Pinazepam Prazepam; Others: Alpidem Barbiturates (e.g., phenobarbital) Carbamates (e.g., meprobamate) Carisoprodol Chlormezanone Ethanol (alcohol) Etifoxine
Hypnotics	Zopiclone
Gabapentinoids (α₂δ VDCC blockers)	Gabapentin Gabapentin enacarbil Phenibut Pregabalin
Antidepressants	SSRIsTooltip Selective serotonin reuptake inhibitors (e.g., escitalopram) SNRIsTooltip Serotonin-norepinephrine reuptake inhibitors (e.g., duloxetine) SARIsTooltip Serotonin antagonist and reuptake inhibitors (e.g., trazodone) TCAsTooltip Tricyclic antidepressants (e.g., clomipramine) TeCAsTooltip Tetracyclic antidepressants (e.g., mirtazapine) MAOIsTooltip Monoamine oxidase inhibitors (e.g., phenelzine); Others: Agomelatine Bupropion Tianeptine Vilazodone Vortioxetine
Antipsychotics	Quetiapine Flupentixol
Sympatholytics (Antiadrenergics)	Alpha-1 blockers (e.g., prazosin) Alpha-2 agonists (e.g., clonidine, dexmedetomidine, guanfacine) Beta blockers (e.g., propranolol)
Others	Benzoctamine Cycloserine Fabomotizole Hydroxyzine Lorpiprazole Mebicar Mepiprazole Nicotine Opipramol Oxaflozane Phenaglycodol Phenibut Picamilon Selank Tiagabine Tofisopam Validolum
WHO-EM Withdrawn from market Clinical trials: Phase III Never to phase III

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 Dimdazenil Doxefazepam Elfazepam Estazolam Ethyl carfluzepate Ethyl dirazepate Ethyl loflazepate Etizolam 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

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References