83396-70-7Relevant academic research and scientific papers
5-(4H)-oxazolones and their benzamides as potential bioactive small molecules
Bermperoglou, Eleftherios,Hadjipavlou-Litina, Dimitra,Mavridis, Evangelos,Pontiki, Eleni
, (2020/08/24)
The five membered heterocyclic oxazole group plays an important role in drug discovery. Oxazolones present a wide range of biological activities. In this article the synthesis of 4-substituted-2-phenyloxazol-5(4H)-ones from the appropriate substituted aldehydes via an Erlenmeyer-Plochl reaction is reported. Subsequently, the corresponding benzamides were produced via a nucleophilic attack of a secondary amine on the oxazolone ring applying microwave irradiation. The compounds are obtained in good yields up to 94percent and their structures were confirmed using IR, 1H-NMR, 13C-NMR and LC/MS data. The in vitro anti-lipid peroxidation activity and inhibitory activity against lipoxygenase and trypsin induced proteolysis of the novel derivatives were studied. Inhibition of carrageenin-induced paw edema (CPE) and nociception was also determined for compounds 4a and 4c. Oxazolones 2a and 2c strongly inhibit lipid peroxidation, followed by oxazolones 2b and 2d with an average inhibition of 86.5percent. The most potent lipoxygenase inhibitor was the bisbenzamide derivative 4c, with IC50 41 μM. The benzamides 3c, 4a-4e and 5c were strong inhibitors of proteolysis. The replacement of the thienyl moiety by a phenyl group does not favor the protection. Compound 4c inhibited nociception higher than 4a. The replacement of thienyl groups by phenyl ring led to reduced biological activity. Docking studies of the most potent LOX inhibitor highlight interactions through allosteric mechanism. All the potent derivatives present good oral bioavailability.
Preparation method of chiral alpha-amino acid
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Paragraph 0067; 0068; 0069, (2016/10/08)
The invention discloses a preparation method of chiral alpha-amino acid. Initial raw materials comprising aldehyde and N-acryl substituted glycine undergo Erlenmeyer-Plochl cyclization, hydrolysis or alcoholysis, asymmetric catalytic hydrogenation and acid hydrolysis to obtain the chiral alpha-amino acid compound. The method adopting the above synthesis route has the advantages of mild reaction conditions, simple technological operation, safe and stable production, realization of high yield, good chemical purity and good optical purity of the above obtained product, wide application range, and suitableness for industrial production.
Palladium-catalyzed diastereo- and enantioselective formal [3 + 2]-cycloadditions of substituted vinylcyclopropanes
Trost, Barry M.,Morris, Patrick J.,Sprague, Simon J.
supporting information, p. 17823 - 17831,9 (2012/12/12)
We describe a palladium-catalyzed diastereo- and enantioselective formal [3 + 2]-cycloaddition between substituted vinylcyclopropanes and electron-deficient olefins in the form of azlactone- and Meldrums acid alkylidenes to give highly substituted cyclopentane products. By modulation of the electronic properties of the vinylcyclopropane and the electron-deficient olefin, high levels of stereoselectivity were obtained. The remote stereoinduction afforded by the catalyst, distal from the chiral pocket generated by the ligand, is proposed to be the result of a new mechanism invoking the Curtin-Hammett principle.
Palladium-catalyzed diastereo- and enantioselective formal [3 + 2]-cycloadditions of substituted vinylcyclopropanes
Trost, Barry M.,Morris, Patrick J.,Sprague, Simon J.
supporting information, p. 17823 - 17831 (2013/01/15)
We describe a palladium-catalyzed diastereo- and enantioselective formal [3 + 2]-cycloaddition between substituted vinylcyclopropanes and electron-deficient olefins in the form of azlactone- and Meldrums acid alkylidenes to give highly substituted cyclopentane products. By modulation of the electronic properties of the vinylcyclopropane and the electron-deficient olefin, high levels of stereoselectivity were obtained. The remote stereoinduction afforded by the catalyst, distal from the chiral pocket generated by the ligand, is proposed to be the result of a new mechanism invoking the Curtin-Hammett principle.
Synthesis and photochemistry of pH-sensitive GFP chromophore analogs
Katritzky, Alan R.,Yoshioka-Tarver, Megumi,El-Gendy, Bahaa El-Dien M.,Hall, C. Dennis
supporting information; experimental part, p. 2224 - 2227 (2011/05/05)
GFP chromophore analogs (7a-e, 8, and 10a,b) containing 2-thienyl-, 5-methyl-2-furyl-, 2-pyrryl, and 6-methyl-2-pyridyl-groups were synthesized and their fluorescence spectra recorded in the pH range 1-7. NMR studies showed that protonation of 8 (2-thieny
Pseudo-peptides derived from isomannide: Inhibitors of serine proteases
Barros, Thalita G.,Pinheiro, Sergio,Williamson,Tanuri, Amilcar,Gomes Jr.,Pereira, Helena S.,Brindeiro,Neto, Jose B. A.,Antunes,Muri, Estela M. F.
scheme or table, p. 701 - 709 (2010/08/05)
In this paper, we describe the synthesis of a novel class of pseudo-peptides derived from isomannide and several oxazolones as potential inhibitors of serine proteases as well as preliminary pharmacological assays for hepatitis C. Hepatitis C, dengue and West Nile fever are among the most important flaviviruses that share one important serine protease enzyme. Serine proteases belong to the most studied class of proteolytic enzymes and are a primary target in the drug development field. Several pseudo-peptides were obtained in good yields from the reaction of isomannide and oxazolones, and their anti-HCV potential using the HCV replicon-based assay was shown.
Novel peptide mimetic inhibitors of hepatitis C serine protease derived from isomannide
Barros, Thalita G.,Pinheiro, Sergio,Williamson, John S.,Tanuri, Amilcar,Pereira, Helena S.,Brindeiro, Rodrigo M.,Neto, Jose B. A.,Antunes, Octavio A. C.,Muri, Estela M. F.
scheme or table, p. 620 - 626 (2009/06/28)
Hepatitis C (HCV) infection is a cause of chronic liver disease such as cirrhosis, carcinoma, or liver failure, and the current therapy is effective in only 50% of patients. Serine proteases, which are present in HCV, are the most studied class of proteolytic enzymes, and are a primary target in the drug development field. In this paper, we describe the synthesis and biological studies of a novel class of peptide mimetic compounds as potential HCV serine protease inhibitors. Georg Thieme Verlag Stuttgart.
Simple one-step syntheses of heterocyclic systems from 2-phenyl-4-thienylmethylidene-5(4H)-oxazolone
Madkour
, p. 81 - 87 (2007/10/03)
The title compound 1a was synthesised and its (Z)-configuration was assigned. The present investigation was intended to study the behavior of 1a towards nitrogen, carbon and oxygen nucleophiles. Thus, treatment of 1a with p-toluidine in ethanol and/or acetic acid afforded the thienylaminomethylidene-5-(4H)-oxazolone 2 and alkenamide 3 together with the imidazolinone 4, respectively. Hydrazinolysis and azidolysis of 1a resulted in the vinylthiophene derivatives 5a,b and the tetrazole 8. The triazine 6 and oxadiazinone 7 were obtained upon the effect of phenylhydrazine and hydroxylamine on 1a respectively. When compound 1a was allowed to react with carbon nucleophiles namely, phenylmagnesium bromide and/or dry benzene under Friedel-Crafts conditions, it gave the acylated product 9 whereas the ester 10 was obtained from the reaction of 1a with sodium ethoxide. In the absence of aromatic hydrocarbon and in acetylene tetrachloride as inert solvent containing anhydrous AlCl3, 1a underwent intramolecular alkylation and/or acylation to afford the respective thieno [3, 2-c] pyridine 11 and cyclopentadieno [b] thiophene 12.
Simple one-step syntheses of heterocyclic systems from2-phenyl-4-thienylmethylidene-5(4H)-oxazolone.
Madkour
, p. 501 - 508 (2007/10/03)
The title compound 1a was synthesised and its (Z)-configuration was assigned. The present investigation was intended to study the behaviour of 1a towards nitrogen, carbon and oxygen nucleophiles. Thus, treatment of 1a with p-toluidine in ethanol and/or acetic acid afforded the thienylaminomethylidene-5(4H)-oxazolone 2 and alkenamide 3 together with the imidazolinone 4, respectively. Hydrazinolysis and azidolysis of 1a resulted in the vinylthiophene derivatives 5a,b and the tetrazole 8. The triazine 6 and oxadiazinone 7 were obtained upon the effect of phenylhydrazine and hydroxylamine on 1a respectively. When compound 1a was allowed to react with carbon nucleophiles namely, phenylmagnesium bromide and/or dry benzene under Friedel-Crafts conditions, it gave the acylated product 9 whereas the ester 10 was obtained from the reaction of 1a with sodium ethoxide. In absence of aromatic hydrocarbon and in acetylene tetrachloride as inert solvent containing anhydrous AlCl3, 1a underwent intramolecular alkylation and/or acylation to afford the respective thieno[3,2-c]pyridine 11 and cyclopentadieno[b] thiophene 12.
5(4H)-oxazolones. Part XIII. A new synthesis of 4-ylidene-5(4H)- oxazolones by the Stille reaction
Beccalli, Egle Maria,Clerici, Francesca,Gelmi, Maria Luisa
, p. 781 - 786 (2007/10/03)
4-Chloromethylene-2-phenyl-5(4H)-oxazolone 1 was used as the starting material for the preparation of a series of 4-ylideneoxazolones 3 by the Stille reaction. When compound 1 was reacted with organostannanes 2 in the presence of the palladium catalyst, o
