- Discovery of Novel Antibiotics as Covalent Inhibitors of Fatty Acid Synthesis
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The steady increase in the prevalence of multidrug-resistant Staphylococcus aureus has made the search for novel antibiotics to combat this clinically important pathogen an urgent matter. In an effort to discover antibacterials with new chemical structure
- Wang, Jia,Ye, Xiaoping,Yang, Xiaohan,Cai, Youyan,Wang, Shengjun,Tang, Jieyu,Sachdeva, Meena,Qian, Yu,Hu, Wenhao,Leeds, Jennifer A.,Yuan, Yanqiu
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- Application of chiral triazole-substituted iodoarenes in the enantioselective construction of spirooxazolines
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A catalytic highly enantioselective synthesis of spirooxazolines is presented. Starting from readily available 2-naphthol-substituted benzamides and using catalytic amounts of a chiral triazole-substituted iodoarene catalyst, a variety of spirooxazolines
- Abazid, Ayham H.,Nachtsheim, Boris J.
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supporting information
p. 8822 - 8825
(2021/09/07)
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- Aryl substituted oxadiazine-one compounds as well as preparation method and application thereof
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The invention discloses aryl substituted oxadiazine-one compounds as well as a preparation method and an application thereof. The structures of the compounds are represented as formula I. The compounds have novel structures, the preparation process is sim
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Paragraph 0067; 0071-0073
(2020/03/17)
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- Design, synthesis and biological evaluation of lazabemide derivatives as inhibitors of monoamine oxidase
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In the studied a series novel of lazabemide derivatives were designed, synthesized and evaluated as inhibitors of monoamine oxidase (MAO-A or MAO-B). These compounds used lazabemide as the lead compound, and the chemistry structures were modified by used the bioisostere and modification of compound with alkyl principle. The two types of inhibitors (inhibition of MAO-A and inhibition of MAO-B) were screened by inhibition activity of MAO. In vitro experiments showed that compounds 3a, 3d and 3f had intensity inhibition the biological activity of MAO-A, while compounds 3i and 3m had intensity inhibition the biological activity of MAO-B. It could be seen from the data of inhibition activity experiments in vitro, that the compound 3d was IC50 = 3.12 ± 0.05 μmol/mL of MAO-A and compound 3m was IC50 = 5.04 ± 0.06 μmol/mL. In vivo inhibition activity experiments were conducted to evaluate the inhibitory activity of compounds 3a, 3d, 3f, 3i and 3m by detecting the contents of 5-HT, NE, DA and activity of MAO-A and MAO-B in plasma and brain tissue. In vivo inhibition activity evaluation results showed that the compounds 3a, 3d, 3f, 3i and 3m had increased the contents of 5-HT, NE and DA in plasma and brain tissues. Meanwhile, the determination results activity of MAO in plasma and brain tissue showed that the compounds 3a, 3d, and 3f had a significant inhibitory effect on the activity of MAO-A, while the compounds 3i and 3m showed inhibitory effect on the activity of MAO-B. This study provided a new inhibitors for inhibiting of MAO activity.
- Zhou, Shiyang,Chen, Guangying,Huang, Gangliang
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p. 4863 - 4870
(2018/08/27)
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- Rate of formation of N-(hydroxymethyl)benzamide derivatives in water as a function of pH and their equilibrium constants
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The third-order rate constants for the pH-dependent formation of the carbinolamides generated from the reaction of formaldehyde and benzamide, 4-chloro, 4-nitro, 4-methyl and 4-methoxybenzamide, are reported. The acid-catalyzed reaction was found to occur via rate-limiting proton transfer, whereas the hydroxide-dependent reaction occurred via a specific-base process. Coupling the rate constants for carbinolamide formation reported herein with the previously established rates for carbinolamide breakdown yielded equilibrium constants for the carbinolamides studied in water.
- Ankem, Ramana V.,Murphy, John L.,Nagorski, Richard W.
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supporting information; scheme or table
p. 6547 - 6549
(2009/04/05)
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- Amidates as leaving groups: Structure/reactivity correlation of the hydroxide-dependent E1cB-like breakdown of carbinolamides in aqueous solution
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(Graph Presented) The kinetic study of the aqueous reaction, between pH 10 and 14, of eight N-(hydroxymethyl)benzamide derivatives in water at 25°C, I = 1.0 M (KCl), has been performed. In all cases, the reaction proceeds via a specific-base-catalyzed deprotonation of the hydroxyl group followed by rate-limiting breakdown of the alkoxide to form aldehyde and amidate (E1cB-like). Such a mechanism was supported by the lack of general buffer catalysis and the first-order dependence of the rate of reaction at low hydroxide concentrations and the transition to zero-order dependence on hydroxide at high concentration. A ρ-value of 0.67 was found for the Hammett correlation between the maximum rate for the hydroxide independent breakdown of the deprotonated carbinolamide (k1) and the substituent on the aromatic ring of the title compounds. Conversely, the substituents on the aromatic ring of the amide portion of the carbinolamide had only a small effect on the Ka of the hydroxyl group indicating that the amide group does not strongly transmit the electronic information of the substituents. These observations led to the conclusion that the major effect of electronic changes on the amide of carbinolamides is reflected in the nucleofugality of the amidate once the alkoxide is formed and not in the pKa of the hydroxyl group of the carbinolamide.
- Tenn III, William J.,Murphy, John L.,Bim-Merle, Jessica K.,Brown, Jason A.,Junia, Adam J.,Price, Malea A.,Nagorski, Richard W.
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p. 6075 - 6083
(2008/02/10)
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- Solvent-free N-hydroxymethylation using formalin over basic alumina
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A convenient and high yield method for N-hydroxymethylation of amines with formalin over basic alumina under solvent-free conditions with microwave heating is described.
- Gupta, Rajive,Paul, Satya,Nanda, Puja
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p. 573 - 574
(2007/10/03)
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- Acyloxymethyl as a Drug Protecting Group. Kinetics and Mechanism of the Hydrolysis of N-Acyloxymethylbenzamides
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Acyloxymethyl derivatives of secondary and tertiary amides undergo hydrolysis via acid-catalysed, base-catalysed and pH-independent processes.The pH-independent pathway involves rate-limiting iminium ion formation and is characterised by the following: a Hammett ρ value for the substituent in the benzamide moiety of ca. -1.2 for both types of substrate; the absence of general-base or nucleophilic catalysis; a common benzoate ion effect; a solvent deuterium isotope effect, kobsH2O/kobsD2O, of ca. 1.6; Σ(excit.) values of -4 and -12 J k-1 mol-1 for secondary and tertiary substrates respectively; and higher reactivity of the tertiary amides over their secondary counterparts.The acid-catalysed process involves protonation of the substrate followed by iminium ion formation, and is characterised by the following: a Hammett ρ value of ca. -1.5 for the substitutent effect of the benzamide moiety; a solvent deuterium isotope effect of ca. 0.4; a monotonic rise in the pseudo-first-order rate constant kobs with increasing ; ΔS(excit.) values > 0 J K-1 mol-1; higher reactivity of the tertiary substrates over their secondary counterparts; and a value of 0.85 for the Bronsted coefficient, βlg, for the carboxylate nucleofuge.The base-catalysed hydrolysis of tertiary substrates involves normal ester hydrolysis via acyl-oxygen bond cleavage, and is characterised by a Hammett ρ value of +0.38, a solvent deuterium isotope effect, kOH-/kOD-, of 0.85, and a ΔS(excit.) balue of -96 J K-1 mol-1.The corressponding base-catalysed process for the secondary substrates involves imine formation via an E2 elimination reaction.The secondary acyloxymethylamides are some 7 * 104 times more reactive than their tertiary counterparts in the base-catalysed region.Hammett ρ values of +1.1 and +0.6 are obtained for the substituents in the base-catalysed region.Hammett ρ values of +1.1 and +0.6 are obtained for the substituents in the ester and amide moieties, respectively.Buffer catalysis is observed, and the value of ca. 0.5 for the Bronsted β coefficient identifies the amide proton as approximately 50percent transferred to the buffer species in the transition state.Heats of formation, ΔHf, calculated using the AM1 SCF MO package reveal that iminium ion formation is thermodynamically equi-energetic for cyclic and acyclic systems.Iminium ion formation from tertiary substrates is favoured by ca. 25 kJ mol-1 over the corresponding secondary analogues.
- Iley, Jim,Moreira, Rui,Rosa, Eduarda
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p. 563 - 570
(2007/10/02)
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