152-72-7 Usage
Chemical Properties
White Crystalline Solid
Originator
Sintrom ,Geigy ,US ,1957
Uses
Different sources of media describe the Uses of 152-72-7 differently. You can refer to the following data:
1. R-Enantiomer of Acenocoumarol. Vitamin K antagonist; structurally similar to Warfarin. Anticoagulant
2. S-Enantiomer of Acenocoumarol. Vitamin K antagonist; structurally similar to Warfarin. Anticoagulant
3. antimicrobial
4. 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.
Check Digit Verification of cas no
The CAS Registry Mumber 152-72-7 includes 6 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 3 digits, 1,5 and 2 respectively; the second part has 2 digits, 7 and 2 respectively.
Calculate Digit Verification of CAS Registry Number 152-72:
(5*1)+(4*5)+(3*2)+(2*7)+(1*2)=47
47 % 10 = 7
So 152-72-7 is a valid CAS Registry Number.
InChI:InChI=1/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
152-72-7Relevant articles and documents
New efficient catalysts in the synthesis of warfarin and acenocoumarol
Ivanov,Manolov,Alexandrova
, p. 521 - 522 (1990)
-
A bis-Lewis basic 2-aminoDMAP/prolinamide organocatalyst for application to the enantioselective synthesis of Warfarin and derivatives
I?ik, Murat,Akkoca, H. Ufuk,Akhmedov, I. Mecido?lu,Tanyeli, Cihangir
, p. 384 - 388 (2016/05/19)
A new chiral sec-amine/amidine-base hybrid catalyst, 2-aminoDMAP/prolinamide, is reported, which is able to catalyze conjugate addition of 4-hydroxycoumarin and various benzylideneacetones, a reaction that directly gives anticoagulant Warfarin and its analogues, with good yields (70-87%) and enantioselectivities (58-72%).
Asymmetric synthesis of warfarin and its analogues on water
Rogozińska-Szymczak, Maria,Mlynarski, Jacek
, p. 813 - 820 (2014/06/23)
The asymmetric Michael addition of 4-hydroxycoumarin to α,β-unsaturated ketones on water without organic co-solvents is reported to be catalysed by organic primary amines. The application of enantiomerically pure (S,S)-diphenylethylenediamine affords a series of important pharmaceutically active compounds in good to excellent yields (73-98%) and with good enantioselectivities (up to 76% ee) via reactions accelerated by ultrasound. In particular, our developments led to an efficient protocol for the 'solids on water' formation of the anticoagulant warfarin in both enantiomeric forms. The presented scalable and environmentally friendly organocatalytic approach affords the target drug in enantiomerically pure form.
