ZK-93423

ZK-93423 is an anxiolytic drug from the β-Carboline family, closely related to abecarnil.[1] 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.[2] It has anticonvulsant, muscle relaxant and appetite stimulating properties comparable to benzodiazepine drugs.[3][4][5][6] 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.[7][8][9][10][11][12]

ZK-93423

Clinical data
ATC code	none
Legal status
Legal status	In general: legal
Identifiers
IUPAC name ethyl 4-(methoxymethyl)-6-(phenylmethoxy) -9H-pyrido[5,4-b]indole-3-carboxylate
CAS Number	83910-44-5^Y
PubChem CID	121926
IUPHAR/BPS	4346
ChemSpider	108771^N
CompTox Dashboard (EPA)	DTXSID101004052
Chemical and physical data
Formula	C23H22N2O4
Molar mass	390.439 g·mol^−1
3D model (JSmol)	Interactive image
SMILES c3ccccc3COc(cc4)cc2c4[nH]c(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^N Key:ALBKMJDFBZVHAK-UHFFFAOYSA-N^N
^NY (what is this?)  (verify)

See also

• ZK-93426

References

1. 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.
2. 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.
3. 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.
4. 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.
5. 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.
6. 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.
7. 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.
8. 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.
9. 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.
10. 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.
11. 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.
12. 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.