12-chloro-9-(2-chlorophenyl)-3-methyl-2,4,5,8-tetraazatricyclo[8.4.0.02,6]tetradeca-1(14),3,5,8,10,12-hexaene

• ChemBase ID: 773
• Molecular Formular: C17H12Cl2N4
• Molecular Mass: 343.20998
• Monoisotopic Mass: 342.04390176
• SMILES: Clc1cc2c(n3c(nnc3C)CN=C2c2c(Cl)cccc2)cc1
• Canonical SMILES: Clc1ccc2c(c1)C(=NCc1n2c(C)nn1)c1ccccc1Cl
• InChI: InChI=1S/C17H12Cl2N4/c1-10-21-22-16-9-20-17(12-4-2-3-5-14(12)19)13-8-11(18)6-7-15(13)23(10)16/h2-8H,9H2,1H3
• InChIKey: JOFWLTCLBGQGBO-UHFFFAOYSA-N

NAMES AND DATABASE IDS

Names

• IUPAC name: 12-chloro-9-(2-chlorophenyl)-3-methyl-2,4,5,8-tetraazatricyclo[8.4.0.0^2,^6]tetradeca-1(14),3,5,8,10,12-hexaene; 12-chloro-9-(2-chlorophenyl)-3-methyl-2,4,5,8-tetraazatricyclo[8.4.0.0^{2,6}]tetradeca-1(10),3,5,8,11,13-hexaene; 12-chloro-9-(2-chlorophenyl)-3-methyl-2,4,5,8-tetraazatricyclo[8.4.0.0^2,^6]tetradeca-1(10),3,5,8,11,13-hexaene
• IUPAC Traditional name: triazolam
• Brand Name: Alti-Triazolam; Apo-Triazo; Clorazolam; Gen-Triazolam; Halcion; Novidorm; Novo-Triolam; Novodorm; Songar
• Synonyms: Triazolam; 8-Chloro-6-[2-chlorophenyl]-1-methyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepine; DEA No. 2887; Triazolamum [INN-Latin]; Triazolam; 8-Chloro-6-(2-chlorophenyl)-1-methyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepine; 8-Chloro-1-methyl-6-(o-chlorophenyl)-4H-s-triazolo[4,3-a][1,4]benzodiazepine; Clorazolam; D II-18-2; Halcion; Novodorm; Songar; U 33030; 三唑仑

Database IDs

• CAS Number: 28911-01-5
• EC Number: 249-307-3
• MDL Number: MFCD00079623
• PubChem SID: 46509147; 24900602; 160964236
• PubChem CID: 5556
• CHEBI ID: 9674
• ATC CODE: N05CD05
• CHEMBL: 646
• Chemspider ID: 5355
• DrugBank ID: DB00897
• KEGG ID: D00387
• Unique Ingredient Identifier: 1HM943223R
• Wikipedia Title: Triazolam
• Medline Plus: a684004

CALCULATED PROPERTIES

JChem

• Acid pKa: 18.078356
• H Acceptors: 3
• H Donor: 0
• LogD (pH = 5.5): 2.864177
• LogD (pH = 7.4): 2.8917372
• Log P: 2.8921
• Molar Refractivity: 103.6838 cm^3
• Polarizability: 35.28183 Å^3
• Polar Surface Area: 43.07 Å^2
• Rotatable Bonds: 1
• Lipinski's Rule of Five: true

ALOGPS 2.1

• Log P: 2.94
• LOG S: -4.27
• Solubility (Water): 1.83e-02 g/l

PROPERTIES

Physical Property

• Solubility: 4.53 mg/L; Methanol
• Apperance: Yellow Solid
• Melting Point: 209-212°C
• Hydrophobicity(logP): 5.5

Safety Information

• Storage Condition: Controlled Substance, -20°C Freezer
• RTECS: XZ5472500
• German water hazard class: 2
• Personal Protective Equipment: Eyeshields, Gloves, type N95 (US), type P1 (EN143) respirator filter
• Drug Control: USDEA Schedule IV; Home Office Schedule 4.1; psychotrope; kontrollierte Droge in Deutschland; regulated under CDSA - not available from Sigma-Aldrich Canada

Pharmacology Properties

• Admin Routes: Oral
• Bioavailability: 44% (oral), 53% (sublingual)
• Excretion: Renal
• Half Life: 1.5-5.5 hours
• Metabolism: Hepatic
• Legal Status: Schedule IV(US)
• Pregnancy Category: X (US)
• Gene Information: human ... GABRA1(2554)

DETAILS

DrugBank - DB00897

• Drug Groups: illicit; approved; withdrawn
• Description: Withdrawn in the United Kingdom due to risk of psychiatric adverse drug reactions. This drug continues to be available in the U.S. Internationally, triazolam is a Schedule IV drug under the Convention on Psychotropic Substances.
• Indication: For the short-term treatment of insomnia.
• Pharmacology: A short-acting benzodiazepine used as a hypnotic agent in the treatment of insomnia. Some countries temporarily withdrew triazolam from the market because of concerns about adverse reactions, mostly psychological, associated with higher dose ranges. Its use at lower doses with appropriate care and labeling has been reaffirmed by the FDA and most other countries. Triazolam has a shorter half-life than chlordiazepoxide, flurazepam, and prazepam and does not generate active metabolites.
• Toxicity: Symptoms of overdose include drowsiness, slurred speech, motor inco-ordination, coma, and respiratory depression.
• Affected Organisms: Humans and other mammals
• Biotransformation: Hepatic. Small amounts of unmetabolized triazolam appear in the urine.
• Absorption: Bioavailability is 44% (oral) and 53% (sublingual).
• Half Life: 1.5-5.5 hours
• Elimination: Triazolam and its metabolites, principally as conjugated glucuronides, which are presumably inactive, are excreted primarily in the urine. Only small amounts of unmetabolized triazolam appear in the urine. The two primary metabolites accounted for 79.9% of urinary excretion.
• References: Rickels K: The clinical use of hypnotics: indications for use and the need for a variety of hypnotics. Acta Psychiatr Scand Suppl. 1986;332:132-41. [Pubmed] ; Oelschlager H: [Chemical and pharmacologic aspects of benzodiazepines] Schweiz Rundsch Med Prax. 1989 Jul 4;78(27-28):766-72. [Pubmed] ; Noguchi H, Kitazumi K, Mori M, Shiba T: Electroencephalographic properties of zaleplon, a non-benzodiazepine sedative/hypnotic, in rats. J Pharmacol Sci. 2004 Mar;94(3):246-51. [Pubmed] ; Tokunaga S, Takeda Y, Shinomiya K, Hirase M, Kamei C: Effects of some H1-antagonists on the sleep-wake cycle in sleep-disturbed rats. J Pharmacol Sci. 2007 Feb;103(2):201-6. Epub 2007 Feb 8. [Pubmed] ; Veje JO, Andersen K, Gjesing S, Kielgast H: [Prescription of tranquilizers and hypnotics in the municipality of Holbaek] Ugeskr Laeger. 1989 Aug 21;151(34):2134-6. [Pubmed]
• External Links: Wikipedia; RxList; PDRhealth; Drugs.com

Sigma Aldrich - T9772

Biochem/physiol Actions
Anxiolytic; ligand for the GABAA receptor benzodiazepine modulatory site.

Toronto Research Chemicals - T767380

Sedative, hypnotic.Controlled substance (depressant).

REFERENCES

• Rickels K: The clinical use of hypnotics: indications for use and the need for a variety of hypnotics. Acta Psychiatr Scand Suppl. 1986;332:132-41. Pubmed
• Oelschlager H: [Chemical and pharmacologic aspects of benzodiazepines] Schweiz Rundsch Med Prax. 1989 Jul 4;78(27-28):766-72. Pubmed
• Noguchi H, Kitazumi K, Mori M, Shiba T: Electroencephalographic properties of zaleplon, a non-benzodiazepine sedative/hypnotic, in rats. J Pharmacol Sci. 2004 Mar;94(3):246-51. Pubmed
• Tokunaga S, Takeda Y, Shinomiya K, Hirase M, Kamei C: Effects of some H1-antagonists on the sleep-wake cycle in sleep-disturbed rats. J Pharmacol Sci. 2007 Feb;103(2):201-6. Epub 2007 Feb 8. Pubmed
• Veje JO, Andersen K, Gjesing S, Kielgast H: [Prescription of tranquilizers and hypnotics in the municipality of Holbaek] Ugeskr Laeger. 1989 Aug 21;151(34):2134-6. Pubmed
• Lomen, P., et al.: J. Int. Med. Res., 4, 55 (1976)
• Allens, G.S., et al.: J. Int. Med. Res., 6, 343 (1976)
• Pakes, G.E., et al.: Drugs, 22, 81 (1981).