N-[(10S)-3,4,5,14-tetramethoxy-13-oxotricyclo[9.5.0.02,7]hexadeca-1(16),2(7),3,5,11,14-hexaen-10-yl]acetamide

• ChemBase ID: 1205
• Molecular Formular: C22H25NO6
• Molecular Mass: 399.437
• Monoisotopic Mass: 399.16818753
• SMILES: O(c1c2c(CC[C@H](NC(=O)C)c3c2ccc(OC)c(=O)c3)cc(OC)c1OC)C
• Canonical SMILES: COc1c(OC)cc2c(c1OC)c1ccc(c(=O)cc1[C@H](CC2)NC(=O)C)OC
• InChI: InChI=1S/C22H25NO6/c1-12(24)23-16-8-6-13-10-19(27-3)21(28-4)22(29-5)20(13)14-7-9-18(26-2)17(25)11-15(14)16/h7,9-11,16H,6,8H2,1-5H3,(H,23,24)/t16-/m0/s1
• InChIKey: IAKHMKGGTNLKSZ-INIZCTEOSA-N

NAMES AND DATABASE IDS

Names

• IUPAC name: N-[(10S)-3,4,5,14-tetramethoxy-13-oxotricyclo[9.5.0.0^2,^7]hexadeca-1(16),2(7),3,5,11,14-hexaen-10-yl]acetamide; N-[(10S)-3,4,5,14-tetramethoxy-13-oxotricyclo[9.5.0.0^2,^7]hexadeca-1(16),2,4,6,11,14-hexaen-10-yl]acetamide; N-[(10S)-3,4,5,14-tetramethoxy-13-oxotricyclo[9.5.0.0^{2,7}]hexadeca-1(16),2,4,6,11,14-hexaen-10-yl]acetamide; N-[(10S)-3,4,5,14-tetramethoxy-13-oxotricyclo[9.5.0.0^{2,7}]hexadeca-1(16),2(7),3,5,11,14-hexaen-10-yl]acetamide
• IUPAC Traditional name: colchicine; N-[(10S)-3,4,5,14-tetramethoxy-13-oxotricyclo[9.5.0.0^2,^7]hexadeca-1(16),2,4,6,11,14-hexaen-10-yl]acetamide
• Brand Name: Colbenemid; Col-probenecid; Condylon; Proben-C
• Synonyms: Colchicine; (S)-N-(1,2,3,10-tetramethoxy-9-oxo-5,6,7,9-tetrahydrobenzo[a]heptalen-7-yl)acetamide; N-[(7S)-1,2,3,10-tetramethoxy-9-oxo-6,7-dihydro-5H-benzo[d]heptalen-7-yl]ethanamide; Colchicin; Colchicina; Colchicinum; Colchicine; N-[(7S)-5,6,7,9-Tetrahydro-1,2,3,10-tetramethoxy-9-oxobenzo[a]heptalen-7-yl]acetamide; (-)-Colchicine; Colchineos; Colchisol; Colcin; Colsaloid; Condylon; NSC 757; (S)-Colchicine >95%; (R)-N-(5,6,7,9-Tetrahydro-1,2,3,10-tetramethoxy-9-oxobenzo[a]heptalen-7-yl)acetamide; (+)-Colchicine; (R)-Colchicine; Colchiceine methyl ether; Artrichine; 秋水仙素; 秋水仙碱

Database IDs

• CAS Number: 64-86-8; 75520-89-7
• EC Number: 200-598-5
• MDL Number: MFCD00078484
• Beilstein Number: 2228813
• Merck Index: 142471
• PubChem SID: 160964667; 24278348; 24892656
• PubChem CID: 6167
• CHEBI ID: 27882
• ATC CODE: M04AC01
• CHEMBL: 107
• Chemspider ID: 5933
• DrugBank ID: DB01394
• IUPHAR ligand ID: 2367
• KEGG ID: D00570
• Unique Ingredient Identifier: SML2Y3J35T
• Wikipedia Title: Colchicine
• Medline Plus: a682711

CALCULATED PROPERTIES

JChem

• Acid pKa: 15.057998
• H Acceptors: 6
• H Donor: 1
• LogD (pH = 5.5): 1.4619884
• LogD (pH = 7.4): 1.4619886
• Log P: 1.4619886
• Molar Refractivity: 111.3756 cm^3
• Polarizability: 41.70993 Å^3
• Polar Surface Area: 83.09 Å^2
• Rotatable Bonds: 5
• Lipinski's Rule of Five: true

ALOGPS 2.1

• Log P: 1.59
• LOG S: -4.16
• Solubility (Water): 2.76e-02 g/l

PROPERTIES

Physical Property

• Solubility: 45 mg/mL at 25 oC [SEIDELL,A (1941)]; Chloroform; DMSO; ethanol: soluble50 mg/mL; Ethyl Acetate; Methanol
• Apperance: Pale Yellow Solid; white to yellow powder; Yellow Solid
• Melting Point: 106-132°C; 150-152°C; 150-160 °C (dec.)(lit.); 155-157°C; ca 150°C dec.
• Optical Rotation: [α]24/D -443°, c = 1.7 in H2O
• Hydrophobicity(logP): 1.30 [HANSCH,C ET AL. (1995)]

Safety Information

• Storage Condition: -20°C Freezer; Room Temperature (15-30°C), Protect from light
• Storage Warning: Light Sensitive
• RTECS: GH0700000
• European Hazard Symbols: Highly toxic (T+)
• UN Number: 1544; UN1544
• German water hazard class: 3
• Hazard Class: 6.1
• Packing Group: 1; I
• Australian Hazchem: 2X
• Risk Statements: 46-28; R:26/28
• Safety Statements: 53-16-26-28-36/37-45; 53-45; S:13-45
• EU Classification: T2
• EU Hazard Identification Number: 6.1B
• Emergency Response Guidebook(ERG) Number: 151
• TSCA Listed: 是
• GHS Pictograms: GHS05; GHS06; GHS08
• GHS Signal Word: Danger
• GHS Hazard statements: H300 + H330-H318-H340; H300-H340
• GHS Precautionary statements: P201-P260-P264-P280-P284-P301 + P310; P281-P301+P310-P321-P308+P313-P405-P501A
• Personal Protective Equipment: Eyeshields, Faceshields, full-face particle respirator type N100 (US), Gloves, respirator cartridge type N100 (US), type P1 (EN143) respirator filter, type P3 (EN 143) respirator cartridges
• RID/ADR: UN 1544 6.1/PG 1

Pharmacology Properties

• Admin Routes: Oral tablets
• Excretion: Primarily feces, urine 10-20%
• Half Life: 9.3 - 10.6 hours
• Legal Status: RX/POM
• Pregnancy Category: X
• Gene Information: human ... ABCB1(5243), CYP3A4(1576)mouse ... Abcb1a(18671), Abcb1b(18669)
• Mechanism of Action: Exact mechanism unknown; Interferes with kinin formation; Leukocyte migration inhibitor; Phagocytosis inhibitor; Reduces phagocytosis with inflammatory; Response abatement

Product Information

• Purity: ≥95% (HPLC); ≥96.0% (HPLC); 95%; 95% (dry wt.)
• Suitability: plant cell culture tested
• Impurities: ≤10% ethyl acetate + H2O; ≤3% water; 10% ethyl acetate and chloroform
• Biological Source: Chief alkaloid from Colchicum autumnale, many other Colchicum spp., several Merendera spp., Gloriosa superba and others (Liliaceae)
• Application(s): Antirheumatic; Cytostatic; Immunosuppressive; Potential HIV inhibitor
• Product Line: BioReagent
• Empirical Formula (Hill Notation): C22H25NO6

DETAILS

MP Biomedicals - 02101406

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MP Biomedicals - 05208170

MP Biomedicals Rare Chemical collection

DrugBank - DB01394

• Drug Groups: approved
• Description: A major alkaloid from Colchicum autumnale L. and found also in other Colchicum species. Its primary therapeutic use is in the treatment of gout, but it has been used also in the therapy of familial Mediterranean fever (periodic disease). [PubChem]
• Indication: For treatment and relief of pain in attacks of acute gouty arthritis.
• Pharmacology: Colchicine is a highly poisonous alkaloid, originally extracted from plants of the genus Colchicum (Autumn crocus, also known as the "Meadow saffron"). Originally used to treat rheumatic complaints and especially gout, it was also prescribed for its cathartic and emetic effects. Its present medicinal use is mainly in the treatment of gout; as well, it is being investigated for its potential use as an anti-cancer drug. It can also be used as initial treatment for pericarditis and preventing recurrences of the condition.
• Toxicity: The onset of toxic effects is usually delayed for several hours or more after the ingestion of an acute overdose. Nausea, vomiting, abdominal pain, and diarrhea occur first. The diarrhea may be bloody due to hemorrhagic gastroenteritis. Burning sensations of the throat, stomach, and skin may be prominent symptoms. Extensive vascular damage may result in shock. Kidney damage, evidenced by hematuria and oliguria, may occur. Muscular weakness may be marked, and ascending paralysis of the central nervous system may develop; the patient usually remains conscious. Delirium and convulsions may occur. Death due to respiratory arrest may result. Although death from the ingestion of as little as 7 mg has been reported, much larger doses have been survived .
• Affected Organisms: Humans and other mammals
• Biotransformation: Probably hepatic. Although colchicine metabolites have not been identified in humans, metabolism by mammalian hepatic microsomes has been demonstrated in vitro.
• Absorption: Colchicine is rapidly absorbed after oral administration, probably from the jejunum and ileum. However, the rate and extent of absorption are variable, depending on the tablet dissolution rate; variability in gastric emptying, intestinal motility, and pH at the absorption site; and the extent to which colchicine is bound to microtubules in gastrointestinal mucosal cells.
• Half Life: Elimination half-life is approximately 1 hour in healthy subjects, although a study with an extended sampling time reported mean terminal elimination half-life values of approximately 9 to 10.5 hours. Other studies have reported half-life values of approximately 2 hours in patients with alcoholic cirrhosis and approximately 2.5 hours in patients with familial Mediterranean fever.
• Protein Binding: Low to moderate (30 to 50%).
• Elimination: In healthy volunteers (n=12) 40 – 65% of 1 mg orally administered colchicine was recovered unchanged in urine.; Enterohepatic recirculation and biliary excretion are also postulated to play a role in colchicine elimination.
• Distribution: * 5 to 8 L/kg [healthy young volunteers]
• Clearance: * 0.17 L/hr/kg [familial Mediterranean fever patients with end-stage renal disease]; * 0.73 L/hr/kg [familial Mediterranean fever patients with normal renal function]
• External Links: Wikipedia; RxList; Drugs.com

DrugBank - DB08117

Drug information: experimental

Sigma Aldrich - C9754

Packaging
1, 5 g in poly bottle
100, 500 mg in poly bottle
Biochem/physiol Actions
Antimitotic agent that disrupts microtubules by binding to tubulin and preventing its polymerization. Stimulates the intrinsic GTPase activity of tubulin. Induces apoptosis in several normal and tumor cell lines and activates the JNK/SAPK signaling pathway.

Sigma Aldrich - C3915

Biochem/physiol Actions
Colchicine is an inhibitor of microtubule polymerization which blocks chromosome segregation during meiosis. Consequently, Colchicine is used to induce polyploidy (tetraploid) in plant cells.

Sigma Aldrich - 855774

Application
For a review summarizing the metabolism and pharmacokinetics of this alkaloid, see Z. Gastroenterol. .1,2

Sigma Aldrich - 27650

Other Notes
Binds specifically with tubulin thus interfering with microtubule organization.1

Toronto Research Chemicals - C640001

The R-enantiomer of Colchicine (C640000). An antimitotic agent that disrupts microtubles by binding to tubulin and preventing its polymerization. Stimulates the intrinsic GTPase activity of tubulin. Induces apoptosis in several normal and tumor cell lin

Toronto Research Chemicals - C640000

An antimitotic agent that disrupts microtubles by binding to tubulin and preventing its polymerization. Stimulates the intrinsic GTPase activity of tubulin. Induces apoptosis in several normal and tumor cell lines and activates the JNK/SAPK signaling pa

REFERENCES

• Lunduena, R.F., et al.: Curr. Opin. Cell Biol., 4, 53 (1992)
• Ceccatelli, S., et al.: Neuroreport, 8, 3779 (1992)
• Want, T.H., et al.: J. Biol. Chem., 273, 4928 (1992)
• Andreu, J.M., et al.: Biochemistry, 37, 8356 (1992)
• Jordan, A., et al.: Med. Res. Rev
• Lunduena, R.F., et al.: Curr. Opin. Cell Biol., 4, 53 (1992)
• Ceccatelli, S., et al.: Neuroreport, 8, 3779 (1992)
• Want, T.H., et al.: J. Biol. Chem., 273, 4928 (1992)
• Andreu, J.M., et al.: Biochemistry, 37, 8356 (1992)
• Jordan, A., et al.: Med. Res. Rev
• J.Am.Coll.Cardiol. (26, No. 6, 1549-57, 1995)
• Local delivery of biodegradable microparticles containing colchicine or a colchicine analogue: effects on restenosis and implications for catheter-based drug delivery.