66-76-2 Usage
Description
Different sources of media describe the Description of 66-76-2 differently. You can refer to the following data:
1. The plants containing dicoumarol mainly include red carnation grass (Trifolium
pratense L., hongchezhoucao), rotten alfalfa (Medicago sativa L., zimuxu), rotten
white vanilla rhinoceros (Melilotus albus Desr., baixiangcaomuxi), and other plants
in Leguminosae.
2. Dicoumarol is a competitive inhibitor of NADH:quinone oxidoreductase (NQO1) with IC50 values of 2.6 and 404 nM in the absence and presence of 2 μM BSA, respectively. It has antiproliferative activity against MIA PaCa-2 pancreas and HCT116 colon carcinoma cells (IC50s = 52 and 19 μM, respectively, after a 96 hour incubation). Dicoumarol inhibits stress-activated protein kinase (SAPK) in HEK293 cells (IC50 = 19-33 μM) at a point upstream of MEKK1 and downstream of TNF receptor-associated factor 2 (TRAF2), and it inhibits TNF-α and LPS-induced NF-κB activation in HeLa cells. It also has antiproliferative activity against FL5.12 lymphocytic and MCF-7 breast carcinoma cells (100 μM) by suppressing JNK activation.
Chemical Properties
white fine crystalline powder
Physical properties
Appearance: white or milky white crystalline powder, slightly fragran; Solubility:
not dissolved in water, ethanol, and ether, slightly dissolved in chloroform, dissolved in alkali solution; Melting point: 287–293?°C.?It can be bluer or with purple
fluorescence in the ultraviolet light.
History
In 1940, Karl Paul Link, a fertile scientist from the University of Wisconsin in the
United States, first isolated the anticoagulant substance from the moldy alfalfa
(Melilotus) and determined its structure. It is a kind of dicoumaroloid substance,
combined by two molecules of coumarin substances. Since this material was found
in the first few years, it has been used as a rodenticide .
In 1979, Conrad et?al. reacted p-nitrobenzene ketone with 4-hydroxycoumarin to
obtain vinegar coumarin, which is basically the same as warfarin in anticoagulant,
but its metabolites also have anticoagulant effect, so the duration of anticoagulation
is longer than warfarin.
Uses
Different sources of media describe the Uses of 66-76-2 differently. You can refer to the following data:
1. Dicumarol is a natural chemical used as an anticoagulant agents that functions as a vitamin K antagonist and is also a derivative of Coumarin.
2. This drug is used for preventing and treating thrombosis, thrombophlebitis, thromboemolium,
and for preventing thrombo-formation in post-operational periods.
Definition
ChEBI: A hydroxycoumarin that is methane in which two hydrogens have each been substituted by a 4-hydroxycoumarin-3-yl group.
Indications
Intravascular thromboembolic diseases include postoperative or postoperative
thrombotic phlebitis, pulmonary embolism, myocardial infarction, and atrial fibrillation caused by embolism.
General Description
Dicumarol, 3,3＇-methylenebis[4-hydroxycoumarin],is a white or creamy white crystalline powderwith a faint, pleasant odor and a slightly bitter taste. It ispractically insoluble in water or alcohol, slightly soluble inchloroform, and dissolved readily by solutions of fixed alkalies.The effects after administration require 12 to 72 hours todevelop and persist for 24 to 96 hours after discontinuance.
Biochem/physiol Actions
Prototype of the 4-hydroxycoumarin class of anticoagulants, which act as vitamin K antagonists, preventing formation of prothrombin. There are many reports that dicumarol also inhibits NADPH:quinone oxidoreductase (NQO(1)). In one, it inhibited NQO(1) in a pancreatic cancer cell line, causing increased formation of superoxide and inhibiting cell growth.
Pharmacology
Dicoumarin is an oral anticoagulant drug and is invalid in?vitro . Dicoumarin is a
coumarin derivative, and its common mechanism is to inhibit synthesis of the coagulation factor in the liver. The structure of dicoumarin is similar to that of vitamin K
and is an antagonist or a competitive inhibitor of vitamin K.?It binds to the vitamin
K epoxide reductase in the liver, inhibits the conversion of vitamin K from epoxide
to hydroquinone, and inhibits the recycling of vitamin K, resulting in that the glutamate side chain of vitamin K-dependent coagulation factors II, VII, IX, and X cannot be carboxylated by γ-carboxy glutamate groups, affecting the binding of
coagulation factor with calcium ion, and thereby inhibiting coagulation, reducing
platelet adhesion, and prolonging thrombosis time . Dicoumarol drugs have no
direct confrontation with synthesized prothrombin and coagulation factor, so it is
ineffective in?vitro. After withdrawal of dicoumarin, prothrombin and coagulation
factors II, IV, IX, and X gradually restore to a certain level, and hence the anticoagulant effect disappear, so its efficacy can be maintained for a long time .
Pharmacokinetics
Dicoumarol is not completely absorbed in the
gastrointestinal tract, often is associated with gastrointestinal discomfort, and is very rarely used
clinically. Today, the only coumarin used in the United States is warfarin, but phenprocoumon and
acenocomumarol are used in Europe.
Clinical Use
Dicumarol is used alone or as an adjunct to heparin in theprophylaxis and treatment of intravascular clotting. It is usedin postoperative thrombophlebitis, pulmonary embolus, acuteembolic and thrombotic occlusion of peripheral arteries, andrecurrent idiopathic thrombophlebitis. It has no effect on analready-formed embolus but may prevent further intravascularclotting. Because the outcome of acute coronary thrombosisdepends largely on extension of the clot and formation ofmural thrombi in the heart chambers, with subsequent embolization,dicumarol has been used in this condition. It hasalso been administered to arrest impending gangrene afterfrostbite. The dose, after determination of the prothrombinclotting time, is 25 to 200 mg, depending on the size and thecondition of the patient. The drug is given orally in the formof capsules or tablets. On the second day and thereafter, itmay be given in amounts sufficient to maintain the prothrombinclotting time at about 30 seconds. If hemorrhages shouldoccur, a dosage of 50 to 100 mg of menadione sodium bisulfiteis injected, supplemented by a blood transfusion.
Side effects
The most serious
adverse reaction of warfarin is bleeding, which can be against by vitamin K, and if
necessary, fresh plasma or whole blood can be injected into the body to confront
bleeding .
Synthesis
Dicoumarol, 3,3′-methylene-bis(4-hydroxycoumarin) (24.1.8), is synthesized
from 4-hydroxycoumarine (24.1.7), which is in turn synthesized from salicylic acid
methyl ester by cyclization to a chromone derivative using sodium or sodium methoxide;
or from o-oxyacetophenone by reacting it with diethylcarbonate in the presence of sodium
ethoxide. Condensation of the resulting 4-hydroxycoumarin with formaldehyde as a phenol
component gives dicoumarol.
Check Digit Verification of cas no
The CAS Registry Mumber 66-76-2 includes 5 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 2 digits, 6 and 6 respectively; the second part has 2 digits, 7 and 6 respectively.
Calculate Digit Verification of CAS Registry Number 66-76:
(4*6)+(3*6)+(2*7)+(1*6)=62
62 % 10 = 2
So 66-76-2 is a valid CAS Registry Number.
InChI:InChI=1/C19H12O6/c20-16-10-5-1-3-7-14(10)24-18(22)12(16)9-13-17(21)11-6-2-4-8-15(11)25-19(13)23/h1-8,20-21H,9H2
66-76-2Relevant articles and documents
Synthesis, characterization, in vitro antimicrobial and anticancer evaluation of random copolyesters bearing biscoumarin units in the main chains
Kandaswamy, Narendran,Raveendiran, Nanthini
, p. 7189 - 7206 (2015)
A series of aliphatic-aromatic random copolyesters bearing a biscoumarin group were synthesized by phase-transfer-catalyzed interfacial polycondensation of 3,3′-methylene-bis(4-hydroxycoumarin)1 and aromatic diols such as hydroquinone, resorcinol, ethyl resorcinol, bisphenol-A, and curcumin with sebacoyl chloride. These copolyesters were obtained with yields in the range between 76 and 85 % and the inherent viscosity between 0.22 and 0.33 dl/g. All the copolyesters were found to be soluble in chlorinated and polar aprotic solvents. The chemical structures of the copolyesters were analyzed by Fourier transform infrared spectroscopy and proton nuclear magnetic resonance (1H-NMR) spectroscopy. The physical properties of copolyesters obtained by altering the aromatic diols 3, were characterized by thermogravimetric analysis, differential scanning calorimetry, gel permeation chromatography, and X-ray diffraction (XRD) technique. Copolyesters exhibited good thermal stability having a decomposition temperature above 223 °C. Copolyesters with the bisphenol group as backbone exhibited higher thermal stability than others. Results revealed that the copolyesters exhibit a glass transition temperature in the range of -11 to 54 °C. It was found that copolyester with ethyl resorcinol and curcumin shown low and high T g values, respectively. XRD measurement revealed the amorphous nature of copolyester with a low degree of crystallinity. Agar disc diffusion method was employed to study the antimicrobial activity of these random copolyesters. The synthesized copolyester was subjected to in vitro anticancer activity against lung cancer (Hep-2) cell line.
Et2AlCl promoted coupling reactions of 4-hydroxy-2-pyrone or 4- hydroxycoumarine with aldehydes: Synthesis of methylenebis(4-hydroxy-2- pyrone) or methylenebis(4-hydroxycoumarine) derivatives
Hagiwara, Hisahiro,Miya, Shigeki,Suzuki, Toshio,Ando, Masayoshi,Yamamoto, Isao,Kato, Michiharu
, p. 493 - 496 (1999)
Methylenebis(4-hydroxy-2-pyrone) or methylenebis(4-hydroxy-coumarine) derivatives (5) have been synthesized from 4-hydroxy-2-pyrones (6) and (8) or 4-hydroxycoumarine (10) with aldehydes (4) in the presence of diethylaluminum chloride.
Fluorescence solvatochromism and modulated anticholinergic activity of novel coumarin compounds sequestered in human serum albumin nanocavities
Rohman, Mostofa Ataur,Baruah, Prayasee,Bhattacharjee, Deboshika,Myrboh,Mitra, Sivaprasad
, p. 18713 - 18725 (2019)
A coumarin compound, 3,3′-methylenebis(4-hydroxy-2H-chromen-2-one) (MHC), and its substituted derivative, 3,3′-(phenylmethylene)bis(4-hydroxy-2H-chromen-2-one) (MHCB), possess potent anticholinergic activities, which were found to be reduced significantly in the presence of human serum albumin (HSA). The molecular interactions responsible for sequestering MHC and MHCB were explored by steady-state and time-resolved fluorescence using the modulated solvatochromic behavior of the probes as a fluorescent marker. A quantitative description of the different solvent parameters responsible for the notable solvent-dependent photo-physical properties of the investigated systems was extracted from multiple linear regression analysis of the experimental data using the Kamlet-Taft and Catalán formalisms. A series of complimentary studies involving circular dichroism measurement and molecular docking calculations revealed that the binding of both coumarin derivatives resulted in the stabilization of the α-helical structure of human serum albumin (HSA). However, significant differences in binding mechanism were noted in terms of the strength, mode and principal forces responsible for the spontaneous association of the probes into the protein-binding domain.
Redox-Triggered Switchable Synthesis of 3,4-Dihydroquinolin-2(1 H)-one Derivatives via Hydride Transfer/ N-Dealkylation/ N-Acylation
Hu, Fangzhi,Li, Sanming,Li, Shuai-Shuai,Wang, Liang,Xu, Lubin,Yang, Xiaoyu
supporting information, p. 358 - 364 (2021/01/13)
The switchable synthesis of 3-non, 3-mono, 3,3′-disubstituted 3,4-dihydroquinolin-2(1H)-ones was developed through a redox-neutral hydride-transfer/N-dealkylation/N-acylation strategy from o-aminobenzaldehyde with 4-hydroxycoumarin, and Meldrum's acid, respectively. The unprecedented strategy for the synthesis of 3,3′-highly functionalized 3,4-dihydroquinolin-2(1H)-one has been realized with the in situ utilization of the released HCHO via the o-QM involved Michael addition. In addition, the synthetic utility of this protocol has been well illustrated via concise synthesis of CYP11B2 inhibitor.
A catalyst-free 1,4-Michael-type reaction of in situ generated ortho-quinone methides (o-QMs) with dithiocarbamic acid salts in water
Aryanasab, Fezzeh,Shabanian, Meisam
, p. 1703 - 1713 (2019/04/17)
Abstract: A catalyst-free conjugate addition of dithiocarbamic acid salts to in situ generated ortho-quinone methides (o-QMs) was investigated for the first time. Several dithiocarbamate derivatives of 4-hydroxycoumarine, 4-hydroxypyrone and 2-naphthol were synthesized in moderate-to-good yields in water at room temperature. Graphical abstract: [Figure not available: see fulltext.] Catalyst-free addition of dithiocarbamic acid salts to in situ generated o-QMs in water at room temperature.
