7-chloro-1-methyl-5-phenyl-2,3-dihydro-1H-1,4-benzodiazepin-2-one

• ChemBase ID: 708
• Molecular Formular: C16H13ClN2O
• Molecular Mass: 284.74022
• Monoisotopic Mass: 284.07164073
• SMILES: Clc1cc2c(N(C(=O)CN=C2c2ccccc2)C)cc1
• Canonical SMILES: Clc1ccc2c(c1)C(=NCC(=O)N2C)c1ccccc1
• InChI: InChI=1S/C16H13ClN2O/c1-19-14-8-7-12(17)9-13(14)16(18-10-15(19)20)11-5-3-2-4-6-11/h2-9H,10H2,1H3
• InChIKey: AAOVKJBEBIDNHE-UHFFFAOYSA-N

NAMES AND DATABASE IDS

Names

• IUPAC name: 7-chloro-1-methyl-5-phenyl-2,3-dihydro-1H-1,4-benzodiazepin-2-one
• IUPAC Traditional name: diazepam
• Brand Name: Diastat, Valium; Alboral; Aliseum; Alupram; Amiprol; An-Ding; Ansiolin; Ansiolisina; Apaurin; Apo-Diazepam; Apozepam; Armonil; Assival; Atensine; Atilen; Bensedin; Bialzepam; Calmocitene; Calmpose; Cercine; Ceregulart; Condition; Diacepan; Dialag; Dialar; Diapam; Diastat; Diazemuls; Diazemulus; Diazepam Intensol; Diazepan; Diazetard; Dienpax; Dipam; Dipezona; Dizac; Domalium; Duksen; Duxen; E-Pam; Eridan; Eurosan; Evacalm; Faustan; Faustan,; Freudal; Frustan; Gewacalm; Gihitan; Kabivitrum; Kiatrium; LA III; La-Iii; Lamra; Lembrol; Levium; Liberetas; Mandrozep; Morosan; Neurolytril; Noan; Novazam; Novo-Dipam; Paceum; Pacitran; Paranten; Paxate; Paxel; Plidan; Pms-Diazepam; Pro-Pam; Q-Pam; Q-Pam Relanium; Quetinil; Quiatril; Quievita; Relaminal; Relanium; Renborin; Ruhsitus; Saromet; Sedapam; Sedipam; Seduksen; Seduxen; Serenack; Serenamin; Serenzin; Servizepam; Setonil; Sibazon; Sibazone; Solis; Sonacon; Stesolid; Stesolin; Tensopam; Tranimul; Tranqdyn; Tranquase; Tranquirit; Tranquo-Puren; Tranquo-Tablinen; Umbrium; Unisedil; Usempax Ap; Valaxona; Valeo; Valiquid; Valitran; Valium; Valrelease; Vatran; Velium; Vival; Vivol; Zetran; Zipan
• Synonyms: Diazepam solution; 7-Chloro-1-methyl-5-phenyl-3H-1,4-benzodiazepin-2(1H)-one; Ro 5-2807; Diazepam; 7-Chloro-1,3-dihydro-1-methyl-5-phenyl-2H-1,4-benzodiazepin-2-one; 1-Methyl-5-phenyl-7-chloro-1,3-dihydro-2H-1,4-benzodiazepin-2-one; Alboral; Aliseum; Alupram; Apaurin; Diacepan; Diaceplex; Dialag; Novazam; Valium; DAP; Methyldiazepinone; Diazepam; 地西泮 溶液; 地西泮

Database IDs

• CAS Number: 439-14-5
• EC Number: 200-659-6; 207-122-5
• MDL Number: MFCD00057323
• PubChem SID: 160964171; 24893306; 24894120; 46505210
• PubChem CID: 3016
• CHEBI ID: 49575
• ATC CODE: N05BA01
• CHEMBL: 12
• Chemspider ID: 2908
• DrugBank ID: DB00829
• IUPHAR ligand ID: 3364
• KEGG ID: D00293
• Unique Ingredient Identifier: Q3JTX2Q7TU
• Wikipedia Title: Diazepam
• Medline Plus: a682047

CALCULATED PROPERTIES

JChem

• H Acceptors: 2
• H Donor: 0
• LogD (pH = 5.5): 3.0749424
• LogD (pH = 7.4): 3.0760722
• Log P: 3.0760865
• Molar Refractivity: 79.8119 cm^3
• Polarizability: 30.31823 Å^3
• Polar Surface Area: 32.67 Å^2
• Rotatable Bonds: 1
• Lipinski's Rule of Five: true

ALOGPS 2.1

• Log P: 2.63
• LOG S: -4.37
• Solubility (Water): 1.22e-02 g/l

PROPERTIES

Physical Property

• Solubility: 45% (w/v) aq 2-hydroxypropyl-β-cyclodextrin: soluble1.6 mg/mL; Chloroform; DMF; DMF: soluble; ethanol: soluble; H2O: slightly soluble; Slightly soluble (50 mg/L)
• Apperance: White to Off-White Solid
• Melting Point: 115-117°C
• Flash Point: 11 °C; 51.8 °F
• Hydrophobicity(logP): 2.9

Safety Information

• Storage Condition: Controlled Substance, -20°C Freezer
• RTECS: DF1575000
• European Hazard Symbols: Flammable (F); Toxic (T); Harmful (Xn)
• UN Number: 1230; 2811
• German water hazard class: 1; 2
• Hazard Class: 3; 6.1
• Packing Group: 2; 3
• Risk Statements: 11-23/24/25-39/23/24/25; 21/22
• Safety Statements: 36/37; 7-16-36/37-45
• GHS Pictograms: GHS02; GHS06; GHS08
• GHS Signal Word: Danger
• GHS Hazard statements: H225-H301-H311-H331-H370; H301 + H311
• GHS Precautionary statements: P210-P260-P280-P301 + P310-P311; P280-P301 + P310-P312
• Personal Protective Equipment: dust mask type N95 (US), Eyeshields, Faceshields, Gloves; Eyeshields, Faceshields, full-face respirator (US), Gloves, multi-purpose combination respirator cartridge (US), type ABEK (EN14387) respirator filter
• RID/ADR: UN 1230 3/PG 2; UN 2811 6.1/PG 3
• Drug Control: Home Office Schedule 4.1; psychotrope; kontrollierte Droge in Deutschland; USDEA Schedule IV; Home Office Schedule 4.1; psychotrope; kontrollierte Droge in Deutschland; regulated under CDSA - not available from Sigma-Aldrich Canada
• Storage Temperature: 2-8°C

Pharmacology Properties

• Admin Routes: Oral, IM, IV, suppository
• Bioavailability: (93-100%)
• Excretion: Renal
• Half Life: 20–100 hours (36-200 hours for main active metabolite desmethyldiazepam)
• Metabolism: Hepatic - CYP2C19
• Legal Status: CD (UK); S4 (Australia); Schedule IV (Canada); Schedule IV (International); Schedule IV (US)
• Pregnancy Category: C (Australia); D (US)
• Gene Information: human ... GABRA1(2554), GABRA2(2555), GABRA3(2556), GABRA5(2558), GABRA6(2559), GABRG2(2566)mouse ... Gabrg2(14406)rat ... Gabra1(29705), Gabra2(29706); human ... GABRA1(2554), GABRA2(2555), GABRA3(2556), GABRA5(2558), GABRA6(2559)rat ... Gabra1(29705), Gabra2(29706)

Product Information

• Concentration: 1.0 mg/mL in methanol; 1.0 mg/mL±5% in methanol
• Grade: analytical standard, for drug analysis

DETAILS

DrugBank - DB00829

• Drug Groups: illicit; approved
• Description: A benzodiazepine with anticonvulsant, anxiolytic, sedative, muscle relaxant, and amnesic properties and a long duration of action. Its actions are mediated by enhancement of gamma-aminobutyric acid activity. It is used in the treatment of severe anxiety disorders, as a hypnotic in the short-term management of insomnia, as a sedative and premedicant, as an anticonvulsant, and in the management of alcohol withdrawal syndrome. (From Martindale, The Extra Pharmacopoeia, 30th ed, p589)
• Indication: Used in the treatment of severe anxiety disorders, as a hypnotic in the short-term management of insomnia, as a sedative and premedicant, as an anticonvulsant, and in the management of alcohol withdrawal syndrome.
• Pharmacology: Diazepam, a benzodiazepine, generates the same active metabolite as chlordiazepoxide and clorazepate. In animals, diazepam appears to act on parts of the limbic system, the thalamus and hypothalamus, and induces calming effects. Diazepam, unlike chlorpromazine and reserpine, has no demonstrable peripheral autonomic blocking action, nor does it produce extrapyramidal side effects; however, animals treated with diazepam do have a transient ataxia at higher doses. Diazepam was found to have transient cardiovascular depressor effects in dogs. Long-term experiments in rats revealed no disturbances of endocrine function. Injections into animals have produced localized irritation of tissue surrounding injection sites and some thickening of veins after intravenous use.
• Toxicity: Symptoms of overdose include somnolence, confusion, coma, and diminished reflexes. Respiration, pulse and blood pressure should be monitored.
• Affected Organisms: Humans and other mammals
• Biotransformation: Hepatic via the Cytochrome P450 enzyme system. The main active metabolite is desmethyldiazepam, in addition to minor active metabolites including temazepam and oxazepam.
• Absorption: Essentially complete, with a bioavailability of 93%.
• Half Life: Biphasic 1-2 days and 2-5 days, active metabolites with long half lives.
• Protein Binding: 98.5%
• Elimination: Diazepam and its metabolites are excreted mainly in the urine, predominantly as their glucuronide conjugates.
• Distribution: * 0.8 to 1.0 L/kg [young healthy males]
• Clearance: * 20-30 mL/min
• References: Mant A, Whicker SD, McManus P, Birkett DJ, Edmonds D, Dumbrell D: Benzodiazepine utilisation in Australia: report from a new pharmacoepidemiological database. Aust J Public Health. 1993 Dec;17(4):345-9. [Pubmed] ; Earley JV, Fryer RI, Ning RY: Quinazolines and 1,4-benzodiazepines. LXXXIX: Haptens useful in benzodiazepine immunoassay development. J Pharm Sci. 1979 Jul;68(7):845-50. [Pubmed] ; Usami N, Yamamoto T, Shintani S, Ishikura S, Higaki Y, Katagiri Y, Hara A: Substrate specificity of human 3(20)alpha-hydroxysteroid dehydrogenase for neurosteroids and its inhibition by benzodiazepines. Biol Pharm Bull. 2002 Apr;25(4):441-5. [Pubmed] ; Oishi R, Nishibori M, Itoh Y, Saeki K: Diazepam-induced decrease in histamine turnover in mouse brain. Eur J Pharmacol. 1986 May 27;124(3):337-42. [Pubmed] ; McLean MJ, Macdonald RL: Benzodiazepines, but not beta carbolines, limit high frequency repetitive firing of action potentials of spinal cord neurons in cell culture. J Pharmacol Exp Ther. 1988 Feb;244(2):789-95. [Pubmed]
• External Links: Wikipedia; RxList; PDRhealth; Drugs.com

Sigma Aldrich - D0899

Biochem/physiol Actions
Benzodiazepine anxiolytic; prototype ligand for the GABAA receptor benzodiazepine modulatory site.

Toronto Research Chemicals - D416855

Diazepam is an anxiolytic; muscle relaxant (skeletal); anticonvulsant.Diazepam is a controlled substance (depressant).

REFERENCES

• Mant A, Whicker SD, McManus P, Birkett DJ, Edmonds D, Dumbrell D: Benzodiazepine utilisation in Australia: report from a new pharmacoepidemiological database. Aust J Public Health. 1993 Dec;17(4):345-9. Pubmed
• Earley JV, Fryer RI, Ning RY: Quinazolines and 1,4-benzodiazepines. LXXXIX: Haptens useful in benzodiazepine immunoassay development. J Pharm Sci. 1979 Jul;68(7):845-50. Pubmed
• Usami N, Yamamoto T, Shintani S, Ishikura S, Higaki Y, Katagiri Y, Hara A: Substrate specificity of human 3(20)alpha-hydroxysteroid dehydrogenase for neurosteroids and its inhibition by benzodiazepines. Biol Pharm Bull. 2002 Apr;25(4):441-5. Pubmed
• Oishi R, Nishibori M, Itoh Y, Saeki K: Diazepam-induced decrease in histamine turnover in mouse brain. Eur J Pharmacol. 1986 May 27;124(3):337-42. Pubmed
• McLean MJ, Macdonald RL: Benzodiazepines, but not beta carbolines, limit high frequency repetitive firing of action potentials of spinal cord neurons in cell culture. J Pharmacol Exp Ther. 1988 Feb;244(2):789-95. Pubmed
• MacDonald, A., et al.: Anal. Profiles Drug Subs., 1, 79 (1972)
• Mandelli, M., et al.: Clin. Pharmacokinet., 3, 72 (1972)
• Bertilsson, L., et al.: Pharmacol. Ther., 45, 85 (1972)
• Murray, J.B., et al.: J. Psychol., 124, 655 (1972)
• Pellock, J.M., et al.: D