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| | ACENOCOUMAROL Basic information |
| | 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 |
| | 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-nitrobenzalacetoneare
thoroughly mixed and heated for 12-14 hours in an oil bath, the temperature
of which is between 135°C and 140°C. After cooling, the melt is dissolved in a
little acetone. The solution is slowly added to a lye made up from 6 parts of
sodium hydroxide in 400 parts of water while stirring and then the mixture is
stirred for 30 minutes. A little animal charcoal is then added, the mixture is
stirred for a further 15 minutes, 400 parts of water are added and the
charcoal and undissolved components are separated by filtration under
suction. The clear solution is made acid to Congo red paper with hydrochloric
acid 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 | | 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 using
p-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 |
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