(1S,5R,13R,14S,17R)-10-methoxy-4-methyl-12-oxa-4-azapentacyclo[9.6.1.01,13.05,17.07,18]octadeca-7(18),8,10,15-tetraen-14-ol

• ChemBase ID: 203
• Molecular Formular: C18H21NO3
• Molecular Mass: 299.36424
• Monoisotopic Mass: 299.15214354
• SMILES: O1[C@@H]2[C@]34[C@H]([C@H](N(CC3)C)Cc3c4c1c(OC)cc3)C=C[C@@H]2O
• Canonical SMILES: COc1ccc2c3c1O[C@@H]1[C@@]43CCN([C@H](C2)[C@@H]4C=C[C@@H]1O)C
• InChI: InChI=1S/C18H21NO3/c1-19-8-7-18-11-4-5-13(20)17(18)22-16-14(21-2)6-3-10(15(16)18)9-12(11)19/h3-6,11-13,17,20H,7-9H2,1-2H3/t11-,12+,13-,17-,18-/m0/s1
• InChIKey: OROGSEYTTFOCAN-DNJOTXNNSA-N

NAMES AND DATABASE IDS

Names

• IUPAC name: (1S,5R,13R,14S,17R)-10-methoxy-4-methyl-12-oxa-4-azapentacyclo[9.6.1.0^1,^1^3.0^5,^1^7.0^7,^1^8]octadeca-7(18),8,10,15-tetraen-14-ol; (1S,5R,13R,14S,17R)-10-methoxy-4-methyl-12-oxa-4-azapentacyclo[9.6.1.0^{1,13}.0^{5,17}.0^{7,18}]octadeca-7(18),8,10,15-tetraen-14-ol
• IUPAC Traditional name: (-)-codeine; codeine
• Brand Name: Codicept; Coducept
• Synonyms: Codeine solution; Codeine; Codeine anhydrous; L-Codeine; Methylmorphine; Morphine monomethyl ether; Norcodeine, N-Methyl; Norcodine, N-Methyl; Codeine; 可待因 溶液; 可待因

Database IDs

• CAS Number: 76-57-3
• EC Number: 200-659-6; 200-969-1
• MDL Number: MFCD00190150
• PubChem SID: 160963666; 46507764; 24892429; 24892819
• PubChem CID: 5284371
• CHEBI ID: 16714
• ATC CODE: N02AA59; N02AA79; R05DA04
• CHEMBL: 485
• Chemspider ID: 4447447
• DrugBank ID: DB00318
• IUPHAR ligand ID: 1673
• KEGG ID: C06174
• Unique Ingredient Identifier: Q830PW7520
• Wikipedia Title: Codeine
• Medline Plus: a682065

CALCULATED PROPERTIES

JChem

• Acid pKa: 13.78274
• H Acceptors: 4
• H Donor: 1
• LogD (pH = 5.5): -1.9427414
• LogD (pH = 7.4): -0.44837403
• Log P: 1.3429513
• Molar Refractivity: 84.6047 cm^3
• Polarizability: 32.610058 Å^3
• Polar Surface Area: 41.93 Å^2
• Rotatable Bonds: 1
• Lipinski's Rule of Five: true

ALOGPS 2.1

• Log P: 1.2
• LOG S: -2.72
• Solubility (Water): 5.77e-01 g/l

PROPERTIES

Physical Property

• Solubility: 9 mg/mL at 20 oC [YALKOWSKY,SH & DANNENFELSER,RM (1992)]
• Flash Point: 11 °C; 51.8 °F
• Hydrophobicity(logP): 1.19 [AVDEEF,A ET AL. (1996)]

Safety Information

• RTECS: QD0893000
• European Hazard Symbols: Flammable (F); Toxic (T); Harmful (Xn)
• UN Number: 1230
• German water hazard class: 1; 3
• Hazard Class: 3
• Packing Group: 2
• Risk Statements: 11-23/24/25-39/23/24/25; 22
• Safety Statements: 36/37; 7-16-36/37-45
• GHS Pictograms: GHS02; GHS06; GHS07; GHS08
• GHS Signal Word: Danger; Warning
• GHS Hazard statements: H225-H301-H311-H331-H370; H302
• GHS Precautionary statements: P210-P260-P280-P301 + P310-P311
• Personal Protective Equipment: dust mask type N95 (US), Eyeshields, Faceshields, Gloves; Eyeshields, Faceshields, full-face respirator (US), Gloves, multi-purpose combination respirator cartridge (US)
• RID/ADR: UN 1230 3/PG 2
• Drug Control: Home Office Schedule 2; stupéfiant; USDEA Schedule II; Home Office Schedule 2; stupéfiant; kontrollierte Droge in Deutschland; regulated under CDSA - not available from Sigma-Aldrich Canada
• Storage Temperature: 2-8°C

Pharmacology Properties

• Admin Routes: Oral, intra-rectally, SC, IM
• Bioavailability: ~90% Oral
• Dependency Liability: Low to moderate
• Half Life: 2.5–3 h
• Metabolism: Hepatic, via CYP2D6 (cytochrome P450 2D6)
• Legal Status: POM (UK); S8 (Australia); Schedule I (Canada); Schedule II (US)
• Pregnancy Category: C (US)
• Gene Information: human ... CYP2D6(1565), OPRD1(4985), OPRK1(4986), OPRM1(4988)rat ... Cyp2d1(266684), Cyp2d2(25053), Cyp2d3(24303), Cyp2d4v1(171522)

Product Information

• Concentration: 1.0 mg/mL±5% in methanol
• Grade: analytical standard, for drug analysis
• Suitability: suitable for 1694 per US EPA

DETAILS

DrugBank - DB00318

• Drug Groups: illicit; approved
• Description: An opioid analgesic related to morphine but with less potent analgesic properties and mild sedative effects. It also acts centrally to suppress cough. [PubChem]
• Indication: For treatment and management of pain (Systemic), also used as an Antidiarrheal and as a cough suppressant.
• Pharmacology: Codeine, an opiate agonist in the CNS, is similar to other phenanthrene derivatives such as morphine. Codeine, in combination with guaifenesin or iodinated glycerol, is used as a cough suppressant and, as a single agent or in combination with acetaminophen or other products, is used for pain control and as an antidiarrheal agent.
• Toxicity: Respiratory depression, sedation and miosis and common symptoms of overdose. Other symptoms include nausea, vomiting, skeletal muscle flaccidity, bradycardia, hypotension, and cool, clammy skin. Apnea and death may ensue.
• Affected Organisms: Humans and other mammals
• Biotransformation: Hepatic. Codeine is a prodrug, itself inactive, but demethylated to the active morphine by the liver enzyme CYP2D6.
• Absorption: Well absorbed following oral administration with a bioavailability of approximately 90%.
• Half Life: 2-4 hours
• Protein Binding: 7-25%
• References: Schroeder K, Fahey T: Over-the-counter medications for acute cough in children and adults in ambulatory settings. Cochrane Database Syst Rev. 2004 Oct 18;(4):CD001831. [Pubmed] ; Vree TB, van Dongen RT, Koopman-Kimenai PM: Codeine analgesia is due to codeine-6-glucuronide, not morphine. Int J Clin Pract. 2000 Jul-Aug;54(6):395-8. [Pubmed] ; Srinivasan V, Wielbo D, Tebbett IR: Analgesic effects of codeine-6-glucuronide after intravenous administration. Eur J Pain. 1997;1(3):185-90. [Pubmed]
• External Links: Wikipedia; RxList; Drugs.com

Sigma Aldrich - C5901

Biochem/physiol Actions
弱麻醉性镇痛剂，作用机理可能是由于可转化成吗啡，其催眠作用较弱；强效镇咳剂

Sigma Aldrich - C1653

Other Notes
Tandem Mass Spectrometry data independently generated by Scripps Center for Metabolomics is available to view or download in PDF. C1653.pdf Tested metabolites are featured on Scripps Center for Metabolomics METLIN Metabolite Database. To learn more, visit sigma.com/metlin.

REFERENCES

• Schroeder K, Fahey T: Over-the-counter medications for acute cough in children and adults in ambulatory settings. Cochrane Database Syst Rev. 2004 Oct 18;(4):CD001831. Pubmed
• Vree TB, van Dongen RT, Koopman-Kimenai PM: Codeine analgesia is due to codeine-6-glucuronide, not morphine. Int J Clin Pract. 2000 Jul-Aug;54(6):395-8. Pubmed
• Srinivasan V, Wielbo D, Tebbett IR: Analgesic effects of codeine-6-glucuronide after intravenous administration. Eur J Pain. 1997;1(3):185-90. Pubmed