129-06-6 Usage
Chemical Properties
Colorless solid
Originator
Coumadin ,Endo,US,1954
Uses
Different sources of media describe the Uses of 129-06-6 differently. You can refer to the following data:
1. Warfarin Sodium (Crystalline Clathrate) is used for pharmaceutical care for patients with chronic heart failure and renal dysfunction.
2. central stimulant
3. Rodenticide.
Manufacturing Process
About 0.1 mol each of 4-hydroxycoumarin and benzalacetone are dissolved, in
any desired order, in about three times their combined weight of pyridine. The
solution is refluxed for about 24 hours, and then allowed to cool; after which
it is poured into about 15 volumes of water, and acidified to about pH 2 by the
addition of hydrochloric acid. An oil separates, and on cooling and standing
overnight solidifies. The solid product is recovered, as by filtration, and
recrystallized from ethanol, according to US Patent 2,427,578.The base melts at about 161°C. It is a white crystalline solid, soluble in hot
ethyl alcohol and substantially insoluble in cold water; it dissolves in alkali
solutions with formation of the salt. The yield is about 40%.
Then, as described in US Patent 2,777,859, warfarin may be reacted with
NaOH to give a sodium salt solution. Crystalline warfarin sodium may be
prepared as described in US Patent 2,765,321.
Brand name
Athrombin (Purdue Frederick); Coumadin (Bristol-Myers
Squibb); Jantoven (USl); Panwarfin (Abbott).
Therapeutic Function
Anticoagulant
General Description
Different sources of media describe the General Description of 129-06-6 differently. You can refer to the following data:
1. Warfarin sodium, 3-( -acetonylbenzyl)-4-hydroxycoumarin sodium salt (Coumadin,Panwarfin), is a white, odorless, crystalline powder, with aslightly bitter taste; it is slightly soluble in chloroform and solublein alcohol or water. A 1% solution has a pH of 7.2 to 8.5.
2. Slightly bitter crystalline powder. An anticoagulant used as a rodenticide.
Reactivity Profile
A coumarin derivative, a lactone. Lactones are similar to esters reactive chemistries.
Health Hazard
Warfarin sodium is highly toxic orally in humans.
Fire Hazard
When heated to decomposition, Warfarin sodium emits toxic fumes of sodium oxide.
Clinical Use
By virtue of its great potency, warfarin sodium at firstwas considered unsafe for use in humans and was used veryeffectively as a rodenticide, especially against rats. At theproper dosage level, however, it can be used in humans, especiallythrough the intravenous route.
Safety Profile
Poison to humans by
ingestion. Experimental poison by ingestion
and intravenous routes. Human systemic
effects by ingestion: dermatitis. Human
reproductive effects by ingestion:
fetotoxicity, abnormal condition of newborn
at birth, other newborn physical effects, and
teratogenic effects includmg developmental
abnormalities of the eye and ear, craniofacial
area, skin and appendages, musculoskeletal
system, cardiovascular system, and
gastrointestinal system of the fetus. ,4n
experimental teratogen. Other experimental
reproductive effects. Mutation data
reported. An anticoagulant drug. When
heated to decomposition it emits toxic
fumes of Na2O.
Veterinary Drugs and Treatments
In veterinary medicine, warfarin is used primarily for the oral,
long-term treatment (or prevention of recurrence) of thrombotic
conditions, primarily in cats, dogs, or horses. Use of warfarin in
veterinary species is somewhat controversial and due to unproven
benefit in reducing mortality, increased expense associated with
monitoring, and potential for serious effects (bleeding), many do
not recommend its use.
Drug interactions
Potentially hazardous interactions with other drugs
There are many significant interactions with warfarin.
Prescribe with care with regard to the following:
Anticoagulant effect enhanced by: alcohol,
amiodarone, anabolic steroids, aspirin, aztreonam,
bicalutamide, cephalosporins, chloramphenicol,
cimetidine, ciprofloxacin, clopidogrel, cranberry
juice, danazol, danshen, dipyridamole, dronedarone,
disulfiram, entacapone, esomeprazole, exenatide,
ezetimibe, fibrates, fluconazole, flutamide, fluvastatin,
glucosamine, grapefruit juice, itraconazole,
ketoconazole, levamisole, levofloxacin, macrolides,
methylphenidate, metronidazole, miconazole,
mirtazepine, nalidixic acid, neomycin, norfloxacin,
NSAIDs, ofloxacin, omeprazole, pantoprazole,
paracetamol, penicillins, proguanil, propafenone,
ritonavir, rosuvastatin, saquinavir, SSRIs, simvastatin,
sulfinpyrazone, sulphonamides, tamoxifen, tegafur,
testosterone, tetracyclines, thyroid hormones,
tigecycline, toremifene, tramadol, trimethoprim,
valproate, venlafaxine, vitamin E and voriconazole.
Anticoagulant effect decreased by: acitretin,
atorvastatin, azathioprine, barbiturates,
carbamazepine, enteral feeds, eslicarbazepine,
enzalutamide, fosphenytoin, ginseng, griseofulvin,
oral contraceptives, phenobarbital, phenytoin,
primidone, rifamycins, St John’s wort (avoid
concomitant use), sucralfate, vitamin K.
Anticoagulant effects enhanced / reduced by: anion
exchange resins, atazanavir, corticosteroids, dietary
changes, disopyramide, efavirenz, fosamprenavir,
nevirapine, ritonavir, telaprevir, tricyclics, trazodone.
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 concomitant use.
Antidiabetic agents: enhanced hypoglycaemic
effect with sulphonylureas; also possible changes to
anticoagulant effect.
Camomile: enhanced anticoagulation.
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,
imatinib and regorafenib; enhanced effect with
capecitabine, etoposide, fluorouracil, ifosfamide,
gefitinib, gemcitabine, sorafenib and vemurafenib;
reduced effect with mercaptopurine and mitotane.
Melatonin: possibly enhanced INR.
Metabolism
The R- and S-isomers are both metabolised in the liver. The
S-isomer is metabolised more rapidly than the R-isomer,
mainly by the cytochrome P450 isoenzyme CYP2C9, which
shows genetic polymorphism. Other isoenzymes are also
involved in the metabolism of the R-isomer.
The metabolites, which have negligible or no
anticoagulant activity, are excreted in the urine following
reabsorption from the bile.
Dose in renal impairment G
Check Digit Verification of cas no
The CAS Registry Mumber 129-06-6 includes 6 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 3 digits, 1,2 and 9 respectively; the second part has 2 digits, 0 and 6 respectively.
Calculate Digit Verification of CAS Registry Number 129-06:
(5*1)+(4*2)+(3*9)+(2*0)+(1*6)=46
46 % 10 = 6
So 129-06-6 is a valid CAS Registry Number.
InChI:InChI=1/C19H16O4.Na/c1-12(20)11-15(13-7-3-2-4-8-13)17-18(21)14-9-5-6-10-16(14)23-19(17)22;/h2-10,15,21H,11H2,1H3;/q;+1
129-06-6Relevant articles and documents
A PROCESS FOR THE PREPARATION OF WARFARIN SODIUM
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Page/Page column 6-8, (2008/06/13)
Provided are novel solvates of Warfarin sodium namely Acetone- ethyl acetate solvate, ethyl acetate solvate, Ethanol-Heptane solvate, Acetone-Heptane solvate and methods for their preparation. Also provided are methods for making Warfarin sodium from Warfarin via the novel solvates.
Preparation of warfarin sodium from warfarin sodium-2-propanol clathrate
-
, (2008/06/13)
The present invention is a method for producing warfarin sodium from warfarin sodium 2-propanol clathrate by thermal, nondestructive solvent expulsion. The solvent expulsion is conducted under conditions of controlled heat transfer whereby the 2-propanol is expelled from the warfarin sodium 2-propanol clathrate without decomposition of warfarin sodium or the clathrate. Heating is conducted the clathrate at a temperature from about 100° C. to about 170° C. in an active oven under air or in an inert atmosphere and at partial pressures ranging from that of a relative vacuum to atmospheric pressure. The invention also relates to pure warfarin sodium prepared according to the method of the invention and pharmaceutical compositions containing warfarin sodium.