- One-Pot Synthesis of 2,5-Disubstituted Furans through In Situ Formation of Allenes and Enolization Cascade
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A one-pot synthesis of 2,5-disubstituted furans from γ-ketoacids is reported. In situ formation of allenoates by action of chloroformate on carboxylic acid following by enolization of ketone affords furan derivatives by cyclization. The reaction was extended to a wide scope of ketoacids and phosphonium salts. This methodology was applied on levulinic acid and derivatives, one of the biosourced platform chemicals.
- Bernhard, Yann,Gilbert, Joachim,Bousquet, Till,Favrelle-Huret, Audrey,Zinck, Philippe,Pellegrini, Sylvain,Pelinski, Lydie
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supporting information
p. 7870 - 7873
(2019/12/24)
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- Kinetics and mechanism of oxidation of substituted 4-oxoacids by N-bromosaccharin
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The kinetics of the oxidation of substituted 4-oxoacids by N-bromosaccharin (NBSac) has been studied in aqueous acetic acid medium at 30 C. The reactions follow first-order kinetics in the 4-oxoacids, NBSA and H+. Variation in the ionic strength has no effect on the reaction rate. The order of reactivity among the studied 4-oxoacids is: 4-methoxy > 4-methyl > 4-phenyl > 4-H > 4-Cl > 4-Br > 3-NO2. The effect of changes in the electronic nature of the substrate revealed that there is a development of positive charge in the transition state. The activation parameters were computed from an Arrhenius plot. Based on the kinetic results, a suitable mechanism has been proposed. The mechanism involves the attack of the oxidizing species hypobromous acidium ion, (H2O+Br).
- Mohamed Farook,Manochitra,Afroos Banu
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p. 239 - 250
(2013/08/24)
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- Synthesis of different substituted pyridazinone derivatives and their anticonvulsant activity
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6-Phenyl(3'-imino-benzylidene)-2,3,4,5-tetrahydro pyridazin-3-one derivatives were synthesized from 6-(3'-aminophenyl)-2,3,4,5-tetrahydro pyridazin-3-one by reaction with different aldehydes. The respective pyridazinone was prepared by cyclization of appropriate β-(aminophenyl) propionic acid with hydrazine hydrate. The pyridazinone derivatives were tested for anticonvulsant activity by MES (maximal electro shock) method and found that few of them have shown significant anticonvulsant activity.
- Samanta, Kartick Chandra,Asif, Mohd.,Pooja,Garg, Vikas,Sharma, Priyanka,Singh, Ravinder
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p. 245 - 251
(2012/02/04)
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- Discovery, synthesis, and structure-activity relationship of 6-aminomethyl-7,8-dihydronaphthalenes as human melanin-concentrating hormone receptor 1 antagonists
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Human melanin-concentrating hormone receptor 1 (hMCHR1) antagonists are promising targets for obesity treatment. We identified the tetrahydronaphthalene derivative 1a with modest binding affinity for hMCHR1 by screening an in-house G protein-coupled receptor (GPCR) ligand library. We synthesized a series of 6-aminomethyl-5,6,7,8-tetrahydronaphthalenes and evaluated their activity as hMCHR1 antagonists. Modification of the biphenylcarbonylamino group revealed that the biphenyl moiety played a crucial role in the interaction of the antagonist with the receptor. The stereoselective effect of the chiral center on binding affinity generated the novel 6-aminomethyl-7,8-dihydronaphthalene scaffold without a chiral center. Optimization of the amino group led to the identification of a potent antagonist 2s (4′-fluoro-N-[6-(1- pyrrolidinylmethyl)-7,8-dihydro-2-naphthalenyl][1,1′-biphenyl] -4-carboxamide), which significantly inhibited the nocturnal food intake in rats after oral administration. Pharmacokinetic analysis confirmed that 2s had good oral bioavailability and brain penetrance. This antagonist appears to be a viable lead compound that can be used to develop a promising therapy for obesity.
- Kamata, Makoto,Yamashita, Toshiro,Imaeda, Toshihiro,Tanaka, Toshio,Terauchi, Jun,Miyamoto, Maki,Ora, Taiichi,Tawada, Michiko,Endo, Satoshi,Takekawa, Shiro,Asami, Asano,Suzuki, Nobuhiro,Nagisa, Yasutaka,Nakano, Yoshihide,Watanabe, Kaoru,Ogino, Hitomi,Kato, Koki,Kato, Kaneyoshi,Ishihara, Yuji
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experimental part
p. 5539 - 5552
(2011/10/17)
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- Homogeneous catalysis of oxovanadium(IV) in the oxidation of substituted 4-oxo acids by bromate in acid medium: A mechanistic study
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Oxovanadium(IV)-catalyzed oxidation of substituted 4-oxo-4-phenyl-butanoic acids (4-oxo acids) by bromate in acid medium leads to the formation of malonic acid and the corresponding benzoic acid. The reaction exhibits first order each in [bromate] and [acid], less than unity order each in [4-oxo acid] and [oxovanadium(IV)], and also shows solvent isotope effect (k(D 2O)/k(H2O) ~ 1.8). The reaction is failed to induce the polymerization of acrylonitrile. The decrease in the rate of reaction with increase in dielectric constant of the medium is observed with all the studied 4-oxo acids. Electron-releasing substituents in the phenyl ring accelerate the rate of oxidation to a large extent, the rate retardation by electron-withdrawing substituents, though perceptible, is not very much. The linear free-energy relationship is characterized by a smooth curve, concaves downward, in the Hammett's plot of log k versus σ, however, Hammett' plots are linear with excellent correlation coefficient, at four temperatures, when Brown and Okamoto's σ+ values are used. The ρ+ values are negative and decrease with increase in temperature. From the intersection of the lines in the Hammett and Arrhenius plots, the isokinetic relationship is discussed. The mechanistic pathway involving the cyclic oxidant-substrate-catalyst ternary complex is proposed, wherein the oxidation state of V(IV) is unaltered. The reaction is an example of the neighboring group participation and intramolecular catalysis.
- Reddy, Cherkupally Sanjeeva,Manjari, Padma Sunitha
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experimental part
p. 76 - 87
(2010/11/18)
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- Kinetics and mechanism of acid bromate oxidation of substituted 4-oxo acids
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Kinetics and mechanism of oxidation of substituted 4-oxo-4-arylbutanoic acids (4-oxo acids) by acid bromate (uncontaminated with Br2) in aqueous acetic acid medium has been studied. The reaction exhibits first order each in [bromate] and [4-oxo acid] and second order in [acid]. Variation in ionic strength has no effect on the reaction rate, while the reaction rates are enhanced on lowering the dielectric constant of the reaction medium. Changing the solvent from H2O to D2O increases the rate of oxidation (kD20/KH20 ~1.8). Electron releasing substituents in the aromatic ring accelerate the reaction rate and electron withdrawing substituents retard it. The order of reactivity among the studied 4-oxo acids is: p-methoxy>> p-methyl p-chloro> m-nitro. The Hammett's plot of log k versus σ is a smooth curve and concaves downward. However, the plot of log k against exalted sigma (Brown's σ+) values is found to be linear with a slope of-1.50 at 313 K. The reaction constant (p+) decreases with increase in temperature. The mechanism proposed involves the attack of the protonated bromate (H2Br +O3) on the enol form of the 4-oxo acid giving the carbocationic bromate ester in the slow step, which undergoes cyclization and then on carbon-carbon bond cleavage yields the products in the fast step. From the intersection of lines in the Hammett and Arrhenius plots, the isokinetic relationship is discussed.
- Reddy, Cherkupally Sanjeeva,Manjari, Padma Sunitha
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experimental part
p. 418 - 424
(2011/01/09)
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- Kinetics of oxidation of 4-oxoacids by N-chlorosaccharin in aqueous acetic acid medium
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The oxidation kinetics of substituted and unsubstituted 4-oxoacids (S) by N-chlorosaccharin (NCSA) have been studied in aqueous acetic acid media. The reaction follows first-order kinetics in each of the 4-oxoacids, NCSA and H +. The effect of changes in the electronic nature of the substrate reveals that positive charge develops in the transition state. Based on the kinetic results and product analysis, a suitable mechanism has been proposed for the reaction of NCSA with 4-oxoacids. Springer Science+Business Media, LLC 2007.
- Farook, N. A. Mohamed
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p. 345 - 356
(2007/12/25)
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- A simple synthesis of α-methyl-γ-keto acids
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The reaction of the anion derived from α-marpholinonitriles with methyl acrylate in excess of NaH in DMF gives γ-keto acids in high yield. This process is highly convenient for the synthesis of various α-substituted-γ-keto acids, which can be easily converted to naturally occurring α-substituted -γ-lactones.
- Pawar,Waghmare,Lokhande
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p. 2549 - 2551
(2007/10/03)
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- 4-phenyl-4-oxo-butanoic acid derivatives with kynurenine-3-hydroxylase inhibiting activity
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4-phenyl-4-oxo-butanoic acid derivatives for use in the treatment of the human or animal body by therepy; particularly as kynurenine-3-hydroxylase inhibitors, in the prevention and/or treatment of a neurodegenerative disease wherein the inhibition of such an enyzme is needed. The present invention further comprises a selected class of the above mentioned 4-phenyl-4-oxo-butanoic acid derivatives, their pharmaceutically acceptable salts, a process for their preparation and pharmaceutical compositions containing them.
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- Syntheses and exploration of new biological activities in ethyl 6/7-substituted and 6, 7-disubstituted quinolin-4-one-3-carboxylates
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Syntheses of a number of ethyl 1H, 4H-quinolin-4-one-3-carboxylates carrying substituted piperidinedione ring at position 6 (25 and 31-35), tetrahydrofuranone (37) or tetrahydropyridazinone ring (39) at position 7 and hydroxy and hydroxymethyl substituent
- Roy, Kamal,Srivastava, Ranjan P.,Tekwani, Babu L.,Pandey, Vikas C.,Bhaduri, Amiya P.
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p. 121 - 126
(2007/10/03)
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- Antiarrhythmic N-aminoalkylene alkyl and aryl sulfonamides
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The present invention provides novel sulfonanilide and benzene-alkylaminium compounds which are the products of processes utilizing novel intermediates. Both the novel compounds and the novel intermediates are useful for the therapeutic or prophylactic treatment of arrhythmic activity.
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