Details of the Drug

General Information of Drug (ID: DMC0JN8)

• Drug Name: GYKI-53655
• Synonyms: GYKI-53655; Gyki 53655; GYKI53655; 1-(4-AMINOPHENYL)-3-METHYLCARBAMOYL-4-METHYL-7,8-METHYLENEDIOXY-3,4-DIHYDRO-5H-2,3-BENZODIAZEPINE; 143692-18-6; CHEMBL267450; LY 300168; SMGACXZFVXKEAX-UHFFFAOYSA-N; AC1L2QV0; GYKI-53655 free base; MLS006010331; SCHEMBL351325; GTPL4209; DTXSID30276296; MolPort-006-418-196; BCP27661; BDBM50048386; ABP000447; NCGC00263113-03; NCGC00263113-01; SMR004701394; LY300168; LY-300168; FT-0765288; LY 300168(GYKI 53655); LY-300168, (+/-)-; 7H-1,3-Dioxolo(4,5-H)(2,3)benzodiazepine-7-carboxamide, 5-(4-aminopheny
• Drug Type: Small molecular drug
• #Ro5 Violations (Lipinski): 0:
  Molecular Weight (mw); 352.4
  Topological Polar Surface Area (xlogp); 2.6
  Rotatable Bond Count (rotbonds); 1
  Hydrogen Bond Donor Count (hbonddonor); 2
  Hydrogen Bond Acceptor Count (hbondacc); 5
• Chemical Identifiers:
  Formula: C19H20N4O3
  IUPAC Name: 5-(4-aminophenyl)-N,8-dimethyl-8,9-dihydro-[1,3]dioxolo[4,5-h][2,3]benzodiazepine-7-carboxamide
  Canonical SMILES: CC1CC2=CC3=C(C=C2C(=NN1C(=O)NC)C4=CC=C(C=C4)N)OCO3
  InChI: InChI=1S/C19H20N4O3/c1-11-7-13-8-16-17(26-10-25-16)9-15(13)18(22-23(11)19(24)21-2)12-3-5-14(20)6-4-12/h3-6,8-9,11H,7,10,20H2,1-2H3,(H,21,24)
  InChIKey: SMGACXZFVXKEAX-UHFFFAOYSA-N
• Cross-matching ID:
  PubChem CID: 126758
  CAS Number: 143692-18-6
  TTD ID: D0M7MW

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Glutamate receptor AMPA (GRIA)	TTAN6JD	NOUNIPROTAC	Inhibitor	[1]
Glutamate receptor AMPA 1 (GRIA1)	TTVPQTF	GRIA1_HUMAN	Inhibitor	[1]

Molecular Expression Atlas of This Drug

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
Glutamate receptor AMPA 1 (GRIA1)	DTT	GRIA1	5.12E-02	-0.4	-0.21
Glutamate receptor AMPA 1 (GRIA1)	DTT	GRIA1	2.97E-01	-4.20E-03	-0.01
Glutamate receptor AMPA (GRIA)	DTT	NO-GeName	5.94E-02	-0.46	-0.15
Glutamate receptor AMPA (GRIA)	DTT	NO-GeName	8.64E-01	-0.52	-0.47

References

• [1] Substituted 1,2-dihydrophthalazines: potent, selective, and noncompetitive inhibitors of the AMPA receptor. J Med Chem. 1996 Jan 19;39(2):343-6.
• [2] Antibodies and venom peptides: new modalities for ion channels. Nat Rev Drug Discov. 2019 May;18(5):339-357.
• [3] Structural investigation of the 7-chloro-3-hydroxy-1H-quinazoline-2,4-dione scaffold to obtain AMPA and kainate receptor selective antagonists. Syn... J Med Chem. 2006 Oct 5;49(20):6015-26.
• [4] Synthesis and AMPA receptor antagonistic activity of a novel 7-imidazolyl-6-trifluoromethyl quinoxalinecarboxylic acid with a substituted phenyl gr... Bioorg Med Chem Lett. 2004 Oct 18;14(20):5107-11.
• [5] The pipeline and future of drug development in schizophrenia. Mol Psychiatry. 2007 Oct;12(10):904-22.
• [6] New 7,8-ethylenedioxy-2,3-benzodiazepines as noncompetitive AMPA receptor antagonists. Bioorg Med Chem Lett. 2006 Jan 1;16(1):167-70.
• [7] Preclinical pharmacology of perampanel, a selective non-competitive AMPA receptor antagonist. Acta Neurol Scand Suppl. 2013;(197):19-24.
• [8] 1H-cyclopentapyrimidine-2,4(1H,3H)-dione-related ionotropic glutamate receptors ligands. structure-activity relationships and identification of pot... J Med Chem. 2008 Oct 23;51(20):6614-8.
• [9] Synthesis of chiral 1-(2'-amino-2'-carboxyethyl)-1,4-dihydro-6,7-quinoxaline-2,3-diones: alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate recep... J Med Chem. 1996 Oct 25;39(22):4430-8.
• [10] Indeno[1,2-b]pyrazin-2,3-diones: a new class of antagonists at the glycine site of the NMDA receptor with potent in vivo activity. J Med Chem. 2000 Jun 15;43(12):2371-81.
• [11] Reduced inhibition of cortical glutamate and GABA release by halothane in mice lacking the K+ channel, TREK-1. Br J Pharmacol. 2007 Nov;152(6):939-45.
• [12] Nat Rev Drug Discov. 2013 Feb;12(2):87-90.
• [13] Eszopiclone: its use in the treatment of insomnia. Neuropsychiatr Dis Treat. 2007 Aug;3(4):441-453.
• [14] Effects of sevoflurane on carrageenan- and fentanyl-induced pain hypersensitivity in Sprague-Dawley rats. Can J Anaesth. 2009 Feb;56(2):126-35.
• [15] Enflurane directly depresses glutamate AMPA and NMDA currents in mouse spinal cord motor neurons independent of actions on GABAA or glycine receptors. Anesthesiology. 2000 Oct;93(4):1075-84.
• [16] Transmembrane residues define the action of isoflurane at the GABAA receptor alpha-3 subunit. Brain Res. 2005 Jan 25;1032(1-2):30-5.
• [17] Glutamatergic and GABAergic modulations of ultrasonic vocalizations during maternal separation distress in mouse pups. Psychopharmacology (Berl). 2009 May;204(1):61-71.
• [18] GABA(A) receptor ligands and their therapeutic potentials. Curr Top Med Chem. 2002 Aug;2(8):817-32.
• [19] Pharmacologic management of Alzheimer disease, Part II: Antioxidants, antihypertensives, and ergoloid derivatives. Ann Pharmacother. 1999 Feb;33(2):188-97.
• [20] Anaesthetic drugs: linking molecular actions to clinical effects. Curr Pharm Des. 2006;12(28):3665-79.