ACENOCOUMAROL CAS 152-72-7

Introduction：Basic information about ACENOCOUMAROL CAS 152-72-7, including its chemical name, molecular formula, synonyms, physicochemical properties, and safety information, etc.

ACENOCOUMAROL Basic information

• Product Name: ACENOCOUMAROL
• Synonyms: acenocoumarin;acenocumarol;acenokumarin;ascumar;g-23,350;g23350;g-23350;Nicoumalone(B.P.1980)
• CAS: 152-72-7
• MF: C19H15NO6
• MW: 353.33
• EINECS: 205-807-3
• Product Categories: Aromatics;Chiral Reagents;Heterocycles;Intermediates & Fine Chemicals;Pharmaceuticals
• Mol File: 152-72-7.mol

ACENOCOUMAROL Chemical Properties

• Melting point: 196-1990C
• Boiling point: 486.76°C (rough estimate)
• density: 1.3979 (rough estimate)
• refractive index: 1.5000 (estimate)
• storage temp.: -20°C Freezer
• solubility: DMSO, heptane and xylene: ≥17mg/mL
• pka: pKa 4.7 (Uncertain)
• form: powder
• color: white to tan
• InChI: 1S/C19H15NO6/c1-11(21)10-15(12-6-8-13(9-7-12)20(24)25)17-18(22)14-4-2-3-5-16(14)26-19(17)23/h2-9,15,22H,10H2,1H3
• InChIKey: VABCILAOYCMVPS-UHFFFAOYSA-N
• SMILES: CC(=O)CC(c1ccc(cc1)[N+]([O-])=O)C2=C(O)c3ccccc3OC2=O

Safety Information

• Hazard Codes: Xn
• Risk Statements: 63-22-36/37/38
• Safety Statements: 26-36/37
• RIDADR: 2811
• WGK Germany: 3
• RTECS: GN4900000
• HS Code: 2932.20.2000
• HazardClass: 6.1(b)
• PackingGroup: III
• Storage Class: 11 - Combustible Solids
• Hazard Classifications: Acute Tox. 4 Oral Eye Irrit. 2 Skin Irrit. 2 STOT SE 3
• Hazardous Substances Data: 152-72-7(Hazardous Substances Data)
• Toxicity: LD50 orally in mice, rats: 1470, 1000 mg/kg (Leroux, Jamain)

ACENOCOUMAROL Usage And Synthesis

Chemical Properties

White Crystalline Solid

Originator

Sintrom ,Geigy ,US ,1957

Uses

R-Enantiomer of Acenocoumarol. Vitamin K antagonist; structurally similar to Warfarin. Anticoagulant

Uses

S-Enantiomer of Acenocoumarol. Vitamin K antagonist; structurally similar to Warfarin. Anticoagulant

Uses

antimicrobial

Uses

Anticoagulant agent: Vitamin K antagonist

Definition

ChEBI: A hydroxycoumarin that is warfarin in which the hydrogen at position 4 of the phenyl substituent is replaced by a nitro group.

Manufacturing Process

16 parts of 4-hydroxycoumarin and 19 parts of 4-nitrobenzalacetonearethoroughly mixed and heated for 12-14 hours in an oil bath, the temperatureof which is between 135°C and 140°C. After cooling, the melt is dissolved in alittle acetone. The solution is slowly added to a lye made up from 6 parts ofsodium hydroxide in 400 parts of water while stirring and then the mixture isstirred for 30 minutes. A little animal charcoal is then added, the mixture isstirred for a further 15 minutes, 400 parts of water are added and thecharcoal and undissolved components are separated by filtration undersuction. The clear solution is made acid to Congo red paper with hydrochloricacid and the product which is precipitated is filtered off under suction. 3-[α-(4'-Nitrophenyl)-β-acetylethyl]-4-hydroxycoumarin is obtained. MP 196-199°C.
It should be noted that the process is akin to that for Warfarin except that 4-nitrobenzalacetone replaces benzalacetone as a raw material.

Therapeutic Function

Anticoagulant, Vitamin

Biological Activity

Acenocoumarol is a warfarin analog, an anticoagulant th at inhibits Vitamin K epoxide reductase. This results in depletion of the reduced form of vitamin K (vitamin KH2), limiting the gamma-carboxylation and subsequent activation of the vitamin K-dependent coagulation factors II, VII, IX, and X and anticoagulant proteins C and S, resulting in decreased prothrombin levels and the amount of thrombin generated.', 'Acenocoumarol is effective against thromboembolic disorders.

Clinical Use

Anticoagulant

Safety Profile

Poison by intraperitoneal route.Moderately toxic by ingestion. A human teratogen by anunspecified route. When heated to decomposition it emitstoxic fumes such as NOx.

Synthesis

Acenocoumarin, 3-(α-acetonyl-p-nitrobenzyl)-4-hydroxycoumarin(24.1.11), is synthesized by a scheme completely analogous to making warfarin, but usingp-nitrobenzalacetone.

Drug interactions

Potentially hazardous interactions with other drugs There are many significant interactions with coumarins. Prescribe with care with regard to the following:
Anticoagulant effect enhanced by: alcohol, amiodarone, anabolic steroids, aspirin, aztreonam, bicalutamide, cephalosporins, chloramphenicol, cimetidine, ciprofloxacin, fibrates, clopidogrel, cranberry juice, danazol, dipyridamole, disulfiram, dronedarone, esomeprazole, ezetimibe, fibrates, fluconazole, flutamide, fluvastatin, grapefruit juice, itraconazole, ketoconazole, levamisole, levofloxacin, macrolides, methylphenidate, metronidazole, miconazole, nalidixic acid, neomycin, norfloxacin, NSAIDs, ofloxacin, omeprazole, pantoprazole, paracetamol, penicillins, propafenone, ritonavir, rosuvastatin, SSRIs, simvastatin, sulfinpyrazone, sulphonamides, tamoxifen, testosterone, tetracyclines, thyroid hormones, tigecycline, toremifene, tramadol, trimethoprim, valproate, vitamin E, voriconazole.
Anticoagulant effect decreased by: acitretin, azathioprine, carbamazepine, enteral feeds, enzalutamide, fosphenytoin, griseofulvin, oral contraceptives, phenobarbital, phenytoin, primidone, rifamycins, St John’s wort (avoid), sucralfate, vitamin K.
Anticoagulant effects enhanced / reduced by: anion exchange resins, corticosteroids, dietary changes, efavirenz, fosamprenavir, tricyclics.
Analgesics: increased risk of bleeding with IV diclofenac and ketorolac - avoid concomitant use.
Anticoagulants: increased risk of haemorrhage with apixaban, dabigatran, edoxaban and rivaroxaban - avoid.
Antidiabetic agents: enhanced hypoglycaemic effect with sulphonylureas also possible changes to anticoagulant effect.
Ciclosporin: there have been a few reports of altered anticoagulant effect; decreased ciclosporin levels have been seen rarely.
Cytotoxics: increased risk of bleeding with erlotinib; enhanced anticoagulant effect with capecitabine, etoposide, fluorouracil, ifosfamide, sorafenib and tegafur; reduced effect with mercaptopurine and mitotane.

Metabolism

Acenocoumarol is extensively metabolised, although the metabolites appear to be pharmacologically inactive in man. 29% is excreted in the faeces and 60% in the urine, with less than 0.2% of the dose being renally excreted unchanged.

ACENOCOUMAROL Preparation Products And Raw materials

• Raw materials: 4-Hydroxycoumarin-->4-Phenyl-1-butene