5-(2-chlorophenyl)-7-nitro-2,3-dihydro-1H-1,4-benzodiazepin-2-one

• ChemBase ID: 939
• Molecular Formular: C15H10ClN3O3
• Molecular Mass: 315.7112
• Monoisotopic Mass: 315.04106888
• SMILES: Clc1c(C2=NCC(=O)Nc3c2cc([N+](=O)[O-])cc3)cccc1
• Canonical SMILES: O=C1CN=C(c2c(N1)ccc(c2)[N+](=O)[O-])c1ccccc1Cl
• InChI: InChI=1S/C15H10ClN3O3/c16-12-4-2-1-3-10(12)15-11-7-9(19(21)22)5-6-13(11)18-14(20)8-17-15/h1-7H,8H2,(H,18,20)
• InChIKey: DGBIGWXXNGSACT-UHFFFAOYSA-N

NAMES AND DATABASE IDS

Names

• IUPAC name: 5-(2-chlorophenyl)-7-nitro-2,3-dihydro-1H-1,4-benzodiazepin-2-one
• IUPAC Traditional name: clonazepam; clonex
• Brand Name: Antelepsin; Antilepsin; Cloazepam; Clonopin; Iktorivil; Klonopin; Klonopin Rapidly Disintegrating; Landsen; Rivotril
• Synonyms: Clonazepamum; Chlonazepam; Clonazepam; 5-(2-Chlorophenyl)-7-nitro-3H-1,4-benzodiazepin-2(1H)-one; Clonazepam; 50(2-Chlorophenyl)-1,3-dihydro-7-nitro-2H-1,4-benzodiazepin-2-one; Ro-5-4023; Clonopin; Iktorivil; Klonopin; Landsen; Rivotril

Database IDs

• CAS Number: 1622-61-3
• EC Number: 216-596-2
• MDL Number: MFCD00057746
• PubChem SID: 24892396; 160964402; 46507677
• PubChem CID: 2802
• CHEBI ID: 3756
• ATC CODE: N03AE01
• CHEMBL: 452
• Chemspider ID: 2700
• DrugBank ID: DB01068
• KEGG ID: D00280
• Unique Ingredient Identifier: 5PE9FDE8GB
• Wikipedia Title: Clonazepam
• Medline Plus: a682279

CALCULATED PROPERTIES

JChem

• Acid pKa: 11.894772
• H Acceptors: 4
• H Donor: 1
• LogD (pH = 5.5): 3.151906
• LogD (pH = 7.4): 3.1519902
• Log P: 3.1520047
• Molar Refractivity: 84.0207 cm^3
• Polarizability: 30.417595 Å^3
• Polar Surface Area: 87.28 Å^2
• Rotatable Bonds: 2
• Lipinski's Rule of Five: true

ALOGPS 2.1

• Log P: 2.76
• LOG S: -4.47
• Solubility (Water): 1.06e-02 g/l

PROPERTIES

Physical Property

• Solubility: <0.1 mg/mL; DMSO
• Apperance: light yellow powder; Tan Solid
• Melting Point: >2250C (dec.)
• Hydrophobicity(logP): 2.7

Safety Information

• Storage Condition: Controlled Substance, -20°C Freezer
• RTECS: DF2100000
• 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, I.M., I.V, sublingual
• Bioavailability: 90%
• Excretion: Renal
• Half Life: 18-50 hours
• Metabolism: Hepatic CYP3A4
• Protein Bound: ~85%
• Legal Status: S4 (Australia); Schedule IV (Canada); Schedule IV (US); schedule Q (UK)
• Pregnancy Category: C (Australia); D (US)
• Gene Information: rat ... Tspo(24230)

DETAILS

DrugBank - DB01068

• Drug Groups: illicit; approved
• Description: An anticonvulsant used for several types of seizures, including myotonic or atonic seizures, photosensitive epilepsy, and absence seizures, although tolerance may develop. It is seldom effective in generalized tonic-clonic or partial seizures. The mechanism of action appears to involve the enhancement of gamma-aminobutyric acid receptor responses. [PubChem]
• Indication: Used as an anticonvulsant in the treatment of the Lennox-Gastaut syndrome (petit mal variant), akinetic and myoclonic seizures.
• Pharmacology: Clonazepam, a benzodiazepine, is used primarily as an anticonvulsant in the treatment of absence seizures, petit mal variant seizures (Lennox-Gastaut syndrome), akinetic and myoclonic seizures, and nocturnal myoclonus.
• Toxicity: Somnolence, confusion, coma, and diminished reflexes
• Affected Organisms: Humans and other mammals
• Biotransformation: Hepatic (cytochrome P450, including CYP3A). Biotransformation occurs mainly by reduction of the 7-nitro group to the 4-amino derivative. This derivative can be acetylated, hydroxylated, and glucuronidated.
• Absorption: Clonazepam is rapidly and completely absorbed after oral administration. The absolute bioavailability of clonazepam is about 90%.
• Half Life: 30-40 hours
• Protein Binding: 85%
• Elimination: Clonazepam is highly metabolized, with less than 2% unchanged clonazepam being excreted in the urine. Metabolites of Klonopin are excreted by the kidneys
• References: Dreifuss FE, Penry JK, Rose SW, Kupferberg HJ, Dyken P, Sato S: Serum clonazepam concentrations in children with absence seizures. Neurology. 1975 Mar;25(3):255-8. [Pubmed] ; Robertson MD, Drummer OH: Postmortem drug metabolism by bacteria. J Forensic Sci. 1995 May;40(3):382-6. [Pubmed] ; Rosen GM, Turner MJ 3rd: Synthesis of spin traps specific for hydroxyl radical. J Med Chem. 1988 Feb;31(2):428-32. [Pubmed] ; Rosen GM, Demos HA, Rauckman EJ: Not all aromatic nitro compounds form free radicals. Toxicol Lett. 1984 Aug;22(2):145-52. [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]
• External Links: Wikipedia; RxList; Drugs.com

Sigma Aldrich - C1277

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

Toronto Research Chemicals - C587080

Antiepileptic agent with anxiolytic and antimanic properties. Anticonvulsant.This is a controlled substance (depressant).

REFERENCES

• Dreifuss FE, Penry JK, Rose SW, Kupferberg HJ, Dyken P, Sato S: Serum clonazepam concentrations in children with absence seizures. Neurology. 1975 Mar;25(3):255-8. Pubmed
• Rosen GM, Turner MJ 3rd: Synthesis of spin traps specific for hydroxyl radical. J Med Chem. 1988 Feb;31(2):428-32. Pubmed
• Rosen GM, Demos HA, Rauckman EJ: Not all aromatic nitro compounds form free radicals. Toxicol Lett. 1984 Aug;22(2):145-52. 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
• Robertson MD, Drummer OH: Postmortem drug metabolism by bacteria. J Forensic Sci. 1995 May;40(3):382-6. Pubmed
• Blum, et al.: Arzneim.-Forsch., 23, 377 (1973)
• Winslow, W.C., et al.: Anal. Profiles Drug Subs., 6, 61 (1977)