Coumarins derivatives

I6I C. Warfarin baits need contain only 0 025% active principle, and rats are killed after ingesting about 5 doses the bait can be left down and the risk of acute toxicity to man or domestic animals is not serious. In common with other coumarin derivatives, warfarin reduces the clotting power of blood and death is caused by haemorrhages initiated by any slight injury. Warfarin is a vitamin K antagonist, and large oral doses of the vitamin can be given as an antidote. 

Weak to moderate chemiluminescence has been reported from a large number of other Hquid-phase oxidation reactions (1,128,136). The Hst includes reactions of carbenes with oxygen (137), phenanthrene quinone with oxygen in alkaline ethanol (138), coumarin derivatives with hydrogen peroxide in acetic acid (139), nitriles with alkaline hydrogen peroxide (140), and reactions that produce electron-accepting radicals such as HO in the presence of carbonate ions (141). In the latter, exemplified by the reaction of h on(II) with H2O2 and KHCO, the carbonate radical anion is probably a key intermediate and may account for many observations of weak chemiluminescence in oxidation reactions. 

The Pechmaim reaction has found extensive appHcations for the synthesis of numerous coumarin derivatives (39). Coumarin derivatives substituted in the pyrone ring can be obtained by condensing phenol with beta-ketoesters. For example, 4-methylcoumarin (3) is obtained with ethyl acetoacetate... 

Photolysis, luminescent properties, and laser activity of coumarin derivatives 97MI27. 

On the other hand, alkaline treatment of coumarin derivatives 108 did not lead to the expected cyclization products 107, but isomerization to the corresponding chromenes 109 took place instead (Scheme 17) (96JHC351). 

Similar cyclization of 367 leading to low yields (20%) of benzodithiine 368 was observed with triethylamine in DMSO (Eq. 32) (76ZOR844). On the other hand, coumarin derivative 369 treated with 1,2-ethanedithiole in the presence of triethylamine provided relatively stable spiro compound 370 (Eq. 33) (89ZOR669). 

Thiourea and allylthiourea (20), D-xylulose (22), sodium diethyldithiocarbamate, L-methionine, and -propyl-di- -propylthiol-carbamate (163), 12 6-(substituted) purines (166), and two coumarin derivatives (164) have been found to promote Striga seed germination. None of these materials, however, appear to be constituents of the natural stimulant preparations. 

Most oral anticoagulants are coumarin derivatives that act via vitamin K antagonism ([2] Fig. 2). Vitamin K... 

The anti-coagulation effect of coumarin derivatives is enhanced... 

Photoredox systems involving carbonyl compounds and amines are used in many applications. Carbonyl compounds employed include benzophenone and derivatives, a-diketones [e.g. benzil, cainphoroquinone (85),2W 291 9,10-phenanthrene quinone], and xanthone and coumarin derivatives. The amines are tertiary and must have a-hydrogens [e.g. N,A7-dimethylani 1 ine, Michler s ketone (86)]. The radicals formed are an a-aminoalkyl radical and a ketyl radical. 

Elastase release from dense granules is monitored with a nonfluorescent substrate containing a coumarin derivative. When the substrate is cleaved, fluorescent aminomethylcoumarin is released. 

The cyclopenta[c]coumarin derivative (12), which occurs with sesquiterpenes in liverworts, has been synthesised in both racemic and enantiomeric forms by lactonisadon and further manipulation of the cyclopentenylbenzene derivative (11) <96SYN863>. Liverworts have been used to illustrate the value of direct nmr analysis of CDCI3 plant extracts <96CC2187>. 

Budzisz E et al. (2003) Cytotoxic effects, alkylating properties and molecular modelling of coumarin derivatives and their phosphonic analogues. Eur J Med Chem 38(6) 597-603... 

Several coumarin derivatives have revealed pronounced medicinal value as antibacterial and antifungal agents [57,58]. Others have displayed antituber-cular activity [59] and some have insecticidal properties [60]. This prompted us to investigate the preparation of a new series of compounds containing coumarin moieties with different side chains or fused rings. 

In a similar manner, 4-hydroxycoumarin reacts with equimolar amounts of 4-aminothiophenol and 4-aminophenol to give the corresponding coumarin derivatives 71a,b (Scheme 21). 

In this review, general and efficient approaches to a diverse series of triazoles and coumarin derivatives have been developed and discussed. The obtained products have been characterized with the help of spectroscopic techniques and were screened for their antiviral and antitumor activity. The methods could provide valuable routes to various coumarin derivatives and enrich the organic and medicinal chemistry of coumarins. The synthesized triazoles and coumarin derivatives showed moderate to good antiviral and antitiunor activities. 

The synthesis of Coumarin derivatives can be made cleaner using zeolite H-BEA and even cationic ion-exchange resin like Amberlyst-15 works. Reactions of resorcinol with acrylic/methacrylic acid, maleic anhydride and esters have been studied (Gunnewegh et al., 1996). 

Coumarin derivatives Cyclosorus interruptus SiOj Hx + AcOEt Vanilin Identification 41 ... 

Irreversible inhibition is probably due to the alkylation of a histidine residue.43 Chymotrypsin is selectively inactivated with no or poor inhibition of human leukocyte elastase (HLE) with a major difference the inactivation of HLE is transient.42,43 The calculated intrinsic reactivity of the coumarin derivatives, using a model of a nucleophilic reaction between the ligand and the methanol-water pair, indicates that the inhibitor potency cannot be explained solely by differences in the reactivity of the lactonic carbonyl group toward the nucleophilic attack 43 Studies on pyridyl esters of 6-(chloromethyl)-2-oxo-2//-1 -benzopyran-3-carboxylic acid (5 and 6, Fig. 11.5) and related structures having various substituents at the 6-position (7, Fig. 11.5) revealed that compounds 5 and 6 are powerful inhibitors of human leukocyte elastase and a-chymotrypsin thrombin is inhibited in some cases whereas trypsin is not inhibited.21... 

Finally, coumarin derivatives may act as general inhibitors of serine proteases or as specific inhibitors of human leukocyte elastase, depending on the nature of the substituents, through two distinct mechanisms, suicide substrates (a-chymotrypsin)... 

SCHEME 11.3 Postulated mechanisms for the inhibition of serine proteases by coumarin derivatives. NuH nucleophile. Pathway a suicide-type inactivation (suicide substrate). Pathway b transient inactivation by formation of a stable acyl-enzyme (alternate substrate-inhibitor). 

Several aryl esters of 6-chloromethyl-2-oxo-2//-l -benzopyran-3-carboxylic acid act as human Lon protease inhibitors (alternate substrate inhibitors)46 without having any effect on the 20S proteasome. Proteasomes are the major agents of protein turnover and the breakdown of oxidized proteins in the cytosol and nucleus of eukaryotic cells,47 whereas Lon protease seems to play a major role in the elimination of oxidatively modified proteins in the mitochondrial matrix. The coumarin derivatives are potentially useful tools for investigating the various biological roles of Lon protease without interfering with the proteasome inhibition. 

Pochet, L. Doucet, C. Dive, G. Wooters,J. Masereel, B. Reboud-Ravaux,M. Pirotte, B. Coumarinic derivatives as mechanism-based inhibitors of a-chymotrypsin and human leukocyte elastase. Bioorg. Med. Chem. 2000, 8, 1489-1501. 

Matricaria recutita, known as German chamomile, is also purported to have antispasmodic properties. It is taken most often as a tea up to four times a day. Benzodiazepine, alcohol, and warfarin users should be cautioned against taking this product because it can cause drowsiness, and it contains coumarin derivatives.20... 

Kashman Y, Gustafson KR, Fuller RW, Cardellina JH, McMahon JB, Currens MJ, Buckheit RW Jr, Hughes SH, Cragg GM, Boyd MR. The calanolides, a novel HIV-inhibitory class of coumarin derivatives from the tropical rainforest tree, Calophylluwi lanigerum. J Med Chem 1992 35 2735-2743. 

Biological monitoring of exposure to coumarin derivatives can be performed by determination of the unchanged compound and/or its metabolites in blood and urine (Table 6). Analytical complexity and the lack of knowledge about the dose-effect relationship in exposed subjects are the primary limitations of this method. 

Van Sittert, N.J. and Tuinman, C.P. (1994) Coumarin derivatives (rodenticides), in Health Surveillance of Pesticide Workers A Manual for Occupational Health Professionals, W. Tordoir, M. Maroni, and F. He (Eds.), Elsevier, Amsterdam, pp. 71-76. 

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