Details of the Drug

General Information of Drug (ID: DMW9NY0)

• Drug Name: Methaqualone
• Synonyms: Methaqualone hydrochloride; Melsedin; Somnofac; Optimil; Parest; Mequal; Melsed HCl; MTQ hydrochloride; Sopor hydrochloride; Somnafac; Quaalude hydrochloride; Methaqualone HCl; Hyminal monohydrochloride; TR 495 monohydrochloride; Mozambin hydrochloride; Methylquinazolone hydrochloride; UNII-RJQ4G25ZRH; 340-56-7; EINECS 206-431-2; NSC 75892; RJQ4G25ZRH; 2-Methyl-3-(o-tolyl)-4-quinazolone hydrochloride; CHI 38; 4(3H)-Quinazolinone, 2-methyl-3-(2-methylphenyl)-, monohydrochloride; 2-Methyl-3-tolylchinazolon-4 hydrochloride [German]

Indication

Disease Entry	ICD 11	Status	REF
Insomnia	7A00-7A0Z	Withdrawn from market	[1]

• Drug Type: Small molecular drug
• #Ro5 Violations (Lipinski): 0:
  Molecular Weight (mw); 250.29
  Topological Polar Surface Area (xlogp); 2.5
  Rotatable Bond Count (rotbonds); 1
  Hydrogen Bond Donor Count (hbonddonor); 0
  Hydrogen Bond Acceptor Count (hbondacc); 2
• ADMET Property:
  BDDCS Class: Biopharmaceutics Drug Disposition Classification System (BDDCS) Class 2: low solubility and high permeability [2]
  Elimination: 0.2% of drug is excreted from urine in the unchanged form [2]
  MRTD: The Maximum Recommended Therapeutic Dose (MRTD) of drug that ensured maximising efficacy and moderate side effect is 19.97581 micromolar/kg/day [3]
  Water Solubility: The ability of drug to dissolve in water is measured as 0.3 mg/mL [2]
• Chemical Identifiers:
  Formula: C16H14N2O
  IUPAC Name: 2-methyl-3-(2-methylphenyl)quinazolin-4-one
  Canonical SMILES: CC1=CC=CC=C1N2C(=NC3=CC=CC=C3C2=O)C
  InChI: InChI=1S/C16H14N2O/c1-11-7-3-6-10-15(11)18-12(2)17-14-9-5-4-8-13(14)16(18)19/h3-10H,1-2H3
  InChIKey: JEYCTXHKTXCGPB-UHFFFAOYSA-N
• Cross-matching ID:
  PubChem CID: 6292
  ChEBI ID: CHEBI:6821
  CAS Number: 72-44-6
  DrugBank ID: DB04833
  TTD ID: D0T7XI
  INTEDE ID: DR1042

Molecular Interaction Atlas of This Drug

Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Cytochrome P450 3A4 (CYP3A4) Main DME	DE4LYSA	CP3A4_HUMAN	Substrate	[4]

References

• [1] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [2] BDDCS applied to over 900 drugs
• [3] Estimating the safe starting dose in phase I clinical trials and no observed effect level based on QSAR modeling of the human maximum recommended daily dose
• [4] Assessment of the stereoselective metabolism of methaqualone in man by capillary electrophoresis. Electrophoresis. 2003 Aug;24(15):2598-607.
• [5] Expression levels and activation of a PXR variant are directly related to drug resistance in osteosarcoma cell lines. Cancer. 2007 Mar 1;109(5):957-65.
• [6] Contribution of human hepatic cytochrome P450 isoforms to regioselective hydroxylation of steroid hormones. Xenobiotica. 1998 Jun;28(6):539-47.
• [7] Comprehensive evaluation of tamoxifen sequential biotransformation by the human cytochrome P450 system in vitro: prominent roles for CYP3A and CYP2D6. J Pharmacol Exp Ther. 2004 Sep;310(3):1062-75.
• [8] Isoform-specific regulation of cytochromes P450 expression by estradiol and progesterone. Drug Metab Dispos. 2013 Feb;41(2):263-9.
• [9] Metabolic interactions between acetaminophen (paracetamol) and two flavonoids, luteolin and quercetin, through in-vitro inhibition studies. J Pharm Pharmacol. 2017 Dec;69(12):1762-1772.
• [10] Potent mechanism-based inhibition of CYP3A4 by imatinib explains its liability to interact with CYP3A4 substrates. Br J Pharmacol. 2012 Apr;165(8):2787-98.
• [11] Effects of morin on the pharmacokinetics of etoposide in rats. Biopharm Drug Dispos. 2007 Apr;28(3):151-6.
• [12] The metabolism of zidovudine by human liver microsomes in vitro: formation of 3'-amino-3'-deoxythymidine. Biochem Pharmacol. 1994 Jul 19;48(2):267-76.
• [13] Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675.