- Modulation of the binding affinity of naproxen to bovine serum albumin by conversion of the drug into amino acid ester salts
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Naproxen (NAP) is one of the most widely prescribed non-steroidal anti-inflammatory drugs. Novel formulations of NAP aiming at better water-solubility, dosage, and the onset of action or new routes of application in order to minimize or prevent side effects of NAP are in the current interest of the pharmaceutical industry. Here, we report the synthesis, chemical, spectral and physicochemical characterization of a series of salts containing cations amino acid alkyl esters (AAE) and NAP anion, which potentially can be used as novel drug formulation. The [L-AAE][NAP] were obtained in three steps: preparation of the AAE hydrochlorides, neutralization of the hydrochlorides to the corresponding AAE, and formation of the target organic salts. All NAP derivatives, tested at a concentration as high as 100 μM, exhibited no toxicity against murine macrophage cell line (RAW 264.7). The binding parameters and stoichiometry of [AAE][NAP]s to bovine serum albumin (BSA) are in the range of that estimated for the parent NAP. Only L-valine isopropyl ester naproxenate characterizes with about one order of magnitude lower binding affinity for BSA, which suggests a faster diffusion rate in the circulatory system than the parent NAP and other derivatives, and therefore faster reach to the target system. Using molecular modeling seven binding pockets of BSA were probed for their suitability to binds the cation and the anion and results are discussed in correlation with the obtained thermodynamic parameters for the binding of NAP derivatives to BSA.
- ?wiatek, Ewelina,Guncheva, Maya,Janus, Ewa,Kardaleva, Proletina,Klebeko, Joanna,Krachmarova, Elena,Ossowicz, Paula,Rangelov, Miroslav,Taneva, Stefka,Todorova, Nadezhda
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Read Online
- Ligand-Enabled γ-C(sp3)–H Acetoxylation of Triflyl-Protected Amines
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A palladium-catalyzed γ-C(sp3)–H acetoxylation of triflyl-protected amines has been achieved. The use of pyridine or 2-alkoxyquinoline-type ligands is key to the success of this transformation. The reaction is highly diastereoselective and easily scalable, and constitutes a direct approach for the synthesis of γ-hydroxy-α-amino acids and β,γ-dihydroxy amines, which are not readily accessible by other routes.
- Jia, Wen-Liang,Fernández-Ibá?ez, M. ángeles
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Read Online
- Optical activity 1,5-substituted-1,3,5-hexahydrotriazine-2-N-nitroimines: Synthesis and insecticidal activity
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Twelve novel neonicotinoid analogues 1-(2-furfuryl)-5-substituted-1,3,5- hexahydrotriazine-2-N-nitroimines 3a, 3b, 3c, 3d, 3e, 3f, 3g, 3h, 3i, 3j, 3k, 3l were synthesized. Their structures were characterized by 1H NMR, IR, and elemental analysis. The preliminary bioassay tests showed that all the title compounds gave ≥90% mortality against Nilaparvata lugen 500 mg/L.
- Xue, Si-Jia,Bu, Hong-Fei,Liu, Li,Xu, Xiao,Ma, Xubo,Zhu, Jun
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Read Online
- Novel naphthylamide derivatives as dual-target antifungal inhibitors: Design, synthesis and biological evaluation
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Fungal infections have become a serious medical problem due to the high infection rate and the frequent emergence of drug resistance. Squalene epoxidase (SE) and 14α-demethylase (CYP51) are considered as the important antifungal targets, they can show the synergistic effect on antifungal therapy. In the study, a series of active fragments were screened through the method of De Novo Link, and these active fragments with the higher Ludi_Scores were selected, which can show the obvious binding ability with the dual targets (SE, CYP51). Subsequently, three series of target compounds with naphthyl amide scaffolds were constructed by connecting these core fragments, and their structures were synthesized. Most of compounds showed the antifungal activity in the treatment of pathogenic fungi. It was worth noting that compounds 10b-5 and 17a-2 with the excellent broad-spectrum antifungal properties also exhibited the obvious antifungal effects against drug-resistant fungi. Preliminary mechanism study has proved these target compounds can block the biosynthesis of ergosterol by inhibiting the activity of dual targets (SE, CYP51). Furthermore, target compounds 10–5 and 17a-2 with low toxicity side effects also demonstrated the excellent pharmacological effects in vivo. The molecular docking and ADMET prediction were performed, which can guide the optimization of subsequent lead compounds.
- An, Yunfei,Dong, Yue,Liu, Min,Han, Jun,Zhao, Liyu,Sun, Bin
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- Ligand-Enabled Copper-Catalyzed N-Alkynylation of Sulfonamide with Alkynyl Benziodoxolone: Synthesis of Amino Acid-Derived Ynamide
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Ynamides are versatile building blocks in organic synthesis. However, the synthesis of amino acid-derived ynamides is difficult but in high demand. Herein, we disclose the copper-catalyzed Csp-N coupling of sulfonamide, including amino acid and peptide derivatives, to give ynamides by using alkynyl benziodoxolones with broad functional group tolerance under mild reaction conditions. The electron-rich bipyridine as a ligand and ethanol as solvent were used for the success of this reaction. The usefulness of the obtained amino acid-derived ynamide as building block was showcased by further derivatization to unique amino acid derivatives. A control experiment to elucidate the mechanistic insight was also described.
- Takai, Ryogo,Shimbo, Daisuke,Tada, Norihiro,Itoh, Akichika
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p. 4699 - 4713
(2021/04/06)
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- Structural Fine-Tuning of Desmuramylpeptide NOD2 Agonists Defines Their in Vivo Adjuvant Activity
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We report on the design, synthesis, and biological evaluation of a series of nucleotide-binding oligomerization-domain-containing protein 2 (NOD2) desmuramylpeptide agonists with improved in vitro and in vivo adjuvant properties. We identified two promising compounds: 68, a potent nanomolar in vitro NOD2 agonist, and the more lipophilic 75, which shows superior adjuvant activity in vivo. Both compounds had immunostimulatory effects on peripheral blood mononuclear cells at the protein and transcriptional levels, and augmented dendritic-cell-mediated activation of T cells, while 75 additionally enhanced the cytotoxic activity of peripheral blood mononuclear cells against malignant cells. The C18 lipophilic tail of 75 is identified as a pivotal structural element that confers in vivo adjuvant activity in conjunction with a liposomal delivery system. Accordingly, liposome-encapsulated 75 showed promising adjuvant activity in mice, surpassing that of muramyl dipeptide, while achieving a more balanced Th1/Th2 immune response, thus highlighting its potential as a vaccine adjuvant.
- Guzelj, Samo,Nabergoj, Sanja,Gobec, Martina,Pajk, Stane,Klan?i?, Veronika,Slütter, Bram,Frkanec, Ru?a,?timac, Adela,?ket, Primo?,Plavec, Janez,Mlinari?-Ra??an, Irena,Jakopin, ?iga
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supporting information
p. 7809 - 7838
(2021/06/28)
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- ANTIVIRAL COMPOUNDS
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The present disclosure describes 4'-fluoromethyl nucleosides for treating viral infections, including Dengue.
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Paragraph 0333
(2021/08/27)
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- Novel peptidomimetic peptide deformylase (PDF) inhibitors of Mycobacterium tuberculosis
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Emergence of MDR-TB and XDR-TB led to the failure of available anti-tubercular drugs. In order to explore, identify and develop new anti-tubercular drugs, novel peptidomimetic series of Mtb–peptide deformylase (PDF) inhibitors was designed and synthesized. In vitro antimycobacterial potential of compounds was established by screening of compounds against Mycobacterium tuberculosis H37Rv strain using MABA. Among them, ester series of compounds 4a, 4b, 4c, 4d, and 4e were found most active, with compound 4c being highly active and exhibiting minimum inhibitory concentration of 6.25?μg/ml against M.?tb H37Rv strain. Additionally, the compounds were docked to determine the probable binding interactions and understand the mechanism of action of most active molecules on Mtb-peptide deformylase (PDF), which is involved in the mycobacterium protein synthesis.
- Gokhale, Kunal M.,Telvekar, Vikas N.
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p. 148 - 156
(2020/08/26)
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- Enhancement of ibuprofen solubility and skin permeation by conjugation with l-valine alkyl esters
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New ibuprofen derivatives were made via conjugation with l-valine alkyl esters (ValOR), where R was changed from an ethyl to a hexyl group. The ionic structure was confirmed using NMR and FTIR. Specific rotation, solubility in commonly used solvents, thermal properties including phase transitions temperatures, and thermal stability were also determined. The ionic structure with a protonated amine group on an l-valine ester and melting points below 100 °C allowed inclusion of these ibuprofen derivatives into the pharmaceutically active protic ionic liquids. The ibuprofen salt solubility in deionised water and two buffer solutions at pH 5.4 and 7.4 were established and compared with the parent acid solubility. The octanol/water (buffer) partition coefficient, permeation through porcine skin, and accumulation in the skin were also measured. Ibuprofen pairing with l-valine alkyl esters [ValOR][IBU], caused higher solubility and a greater drug molecule absorption through biological membranes. log?P was lower for ibuprofen salts than for the acid and it increased with a longer l-valine ester cation alkyl chain. In vitro porcine skin tests showed that ibuprofen salts with a propyl or isopropyl ester in l-valine are particularly relevant for topical application. They provide transport for ibuprofen through the skin at much higher rate than the unmodified acid and a higher permeated ibuprofen concentration, which can improve efficacy. Thus, synthesised ibuprofen derivatives could be used as drug carriers in transdermal systems to provide better drug bioavailability, and they can be also be the source of exogenous l-valine.
- Janus, Ewa,Ossowicz, Paula,Klebeko, Joanna,Nowak, Anna,Duchnik, Wiktoria,Kucharski, ?ukasz,Klimowicz, Adam
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p. 7570 - 7584
(2020/03/10)
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- Potent arylamide derivatives as dual-target antifungal agents: Design, synthesis, biological evaluation, and molecular docking studies
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Fungal infections have become a serious medical problem due to the high infection rate and the frequent emergence of drug resistance. Ergosterol is an important structural component of the fungal cell membrane, its synthetases (squalene epoxidase (SE) and 14α-demethylase (CYP51)) are considered as the key points to block the ergosterol synthesis. In this study, we designed a series of dual-target arylamides derivatives based on the analysis of active sites (SE, CYP51). Subsequently, these target compounds were synthesized, and their antifungal activity was evaluated. Most of compounds demonstrate the potent antifungal activity against multiple Candida spp. and A. fum. In particular, the antifungal activities of compounds 10b and 11c are not only superior to positive control drugs, but also have significant inhibitory effects on drug-resistant fungi (C.alb. Strain100, C.alb. Strain103). Therefore, their action mechanism was further studied. Cellular uptake and electron microscopy observation showed that target compounds were able to enter fungal cytoplasmic region through free diffusion, and destroyed cell membrane structure. At the same time, preliminary mechanisms have demonstrated that they can affect the synthesis of ergosterol by inhibiting the activity of dual targets. It is worth noting that they also can exhibit excellent antifungal activity and low toxic side effects in vivo. Their ADMET properties and binding models were established will be useful for further lead optimization.
- An, Yunfei,Dong, Yue,Han, Jun,Liu, Min,Liu, Xinyong,Sun, Bin
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- A valine ester hydrochloride synthetic method (by machine translation)
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The invention relates to a valine ester hydrochloride synthetic method, at room temperature, anhydrous hydrogen chloride gas access is provided with the valine and alkyl alcohol of the reaction solvent in the reaction vessel to saturation, then stop ventilation, the system for heating to flow back to the completion of the reaction, the reaction process of tail gas in absorption, resulting absorption solution is used as the reaction solvent. The advantage of this invention is characterized in that: the invention will be valine and acidified alkyl alcohol reaction under normal temperature acyclic alkyl ester hydrochloride, the recycling of exhaust gas chlorination process, the process conditions are mild, the device does not have strict requirement, therefore, the process is simple, the operation is simple, high safety, low production cost, small influence on the environment. (by machine translation)
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Paragraph 0017; 0018
(2019/01/06)
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- Carbon Dioxide-Mediated C(sp3)-H Arylation of Amine Substrates
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Elaborating amines via C-H functionalization has been an important area of research over the past decade but has generally relied on an added directing group or sterically hindered amine approach. Since free-amine-directed C(sp3)-H activation is still primarily limited to cyclization reactions and to improve the sustainability and reaction scope of amine-based C-H activation, we present a strategy using CO2 in the form of dry ice that facilitates intermolecular C-H arylation. This methodology has been used to enable an operationally simple procedure whereby 1° and 2° aliphatic amines can be arylated selectively at their γ-C-H positions. In addition to potentially serving as a directing group, CO2 has also been demonstrated to curtail the oxidation of sensitive amine substrates.
- Kapoor, Mohit,Liu, Daniel,Young, Michael C.
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supporting information
p. 6818 - 6822
(2018/05/31)
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- Discovery of nanomolar desmuramylpeptide agonists of the innate immune receptor nucleotide-binding oligomerization domain-containing protein 2 (NOD2) possessing immunostimulatory properties
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Muramyl dipeptide (MDP), a fragment of bacterial peptidoglycan, has long been known as the smallest fragment possessing adjuvant activity, on the basis of its agonistic action on the nucleotide-binding oligomerization domain-containing protein 2 (NOD2). There is a pressing need for novel adjuvants, and NOD2 agonists provide an untapped source of potential candidates. Here, we report the design, synthesis, and characterization of a series of novel acyl tripeptides. A pivotal structural element for molecular recognition by NOD2 has been identified, culminating in the discovery of compound 9, the most potent desmuramylpeptide NOD2 agonist to date. Compound 9 augmented pro-inflammatory cytokine release from human peripheral blood mononuclear cells in synergy with lipopolysaccharide. Furthermore, it was able to induce ovalbumin-specific IgG titers in a mouse model of adjuvancy. These findings provide deeper insights into the structural requirements of desmuramylpeptides for NOD2-activation and highlight the potential use of NOD2 agonists as adjuvants for vaccines.
- Gobec, Martina,Toma?i?, Tihomir,?timac, Adela,Frkanec, Ru?a,Trontelj, Jurij,Anderluh, Marko,Mlinari?-Ra??an, Irena,Jakopin, ?iga
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supporting information
p. 2707 - 2724
(2018/04/23)
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- Preparation and purification method of valsartan
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The invention relates to the field of medicinal chemistry and discloses a preparation and purification method of valsartan. The method comprises the steps of (S1) adding L-valine and alcohol to a reaction kettle, slowly dropwise adding thionyl chloride, carrying out heating reflux reaction, adding isopropyl acetate for pulping, carrying out suction filtration to obtain an intermediate 1; (S2) carrying out nucleophilic reaction on the intermediate 1 and a starting material 2 in a solvent under an alkaline condition to obtain an intermediate 2; (S3) carrying out nucleophilic reaction on the intermediate 2 and valeryl chloride in the solvent under the alkaline condition to obtain an intermediate 3; and (S4) carrying out cyclization reaction on the intermediate 3, sodium azide and a catalyst ((-)-sparteine-Cu (II) complex) in the solvent, washing, crystallizing and drying to obtain the valsartan. The sodium azide and the catalyst ((-)-sparteine-Cu (II) complex) are used in the cyclization reaction, and the cyclization yield can reach 90%. According to the purification method, the purity of the raw materials of the valsartan is greater than 99.99%, the content of a solvent residue (ethyl acetate) is smaller than 0.5%, the content of a specific impurity is smaller than 0.1%, other unknown individual impurities are avoided and an enantiomer impurity is not detected.
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Paragraph 0058; 0059; 0060; 0061
(2017/10/13)
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- Orthogonally Protected Sch?llkopf's Bis-lactim Ethers for the Asymmetric Synthesis of α-Amino Acid Derivatives and Dipeptide Esters
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Alkylation of the aza-enolates of orthogonally protected chiral bis-lactim ethers with electrophiles proceeds with good levels of diastereocontrol to afford trans-alkylated adducts that can be efficiently deprotected via hydrolysis/hydrogenation procedures to afford non-proteinogenic α-amino acid or dipeptide ester derivatives.
- Hutchby, Marc,Sedgwick, Adam C.,Bull, Steven D.
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p. 2036 - 2049
(2016/07/06)
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- Synthesis of novel nucleoside analogue phosphorothioamidate prodrugs and in vitro anticancer evaluation against RKO human colon carcinoma cells
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Novel phosphorothioamidates of pyrimidine nucleoside analogues have been prepared and evaluated in vitro against RKO human colon cancer cell by the MTT cytotoxicity assay. The parent nucleoside analogues were inactive in this assay, while the phosphorothioamidate prodrugs were active at low uM levels in some cases. The O-isopropyl phosphorothioamidate of 2 ′,3 ′-O- isopropylidene-uridine containing the L-phenylalanine ethyl ester 6f was the most active at 148 uM, a 10-fold enhancement in anticancer activity compared with the parent nucleoside 2 with no increase in cytotoxicity.
- Liu, Wei,Zhang, Lin,Zhou, Honggang,Yang, Cheng,Miao, Zhiwei,Zhao, Yufen
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p. 161 - 173
(2013/06/04)
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- Antimicrobial toxicity studies of ionic liquids leading to a 'hit' MRSA selective antibacterial imidazolium salt
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Imidazolium salts can be classed as surfactants, detergents, ionic liquids, reagents, catalysts or solvents. A study of the toxicity and ecotoxicity of these salts yields valuable information for their use as pharmaceuticals as well as impact on the environment. Our approach to screen a series of chiral imidazolium salts for toxicity to bacteria and fungi, including clinical pathogen strains, has led to the identification of a 'hit' MRSA selective antimicrobial compound. Preliminary structure-activity-relationship (SAR) information (required position of l-phenylalanine and l-valine group) is also elucidated within this first generation of compounds. Conversely, most of the imidazolium salts were nontoxic (IC95 > 2 mM) to the 12 fungi strains and 8 bacteria strains screened, and we propose that they are suitable candidates for 'green chemistry' applications. Ecotoxicity studies (Biodegradation ISO 14593 'CO2 Headspace Test') of two bromide ionic liquids containing l-phenylalanine residues indicate that these ionic liquids passed the test (>60% in 28 days) and classed as readily biodegradable.
- Coleman, Deborah,Spulak, Marcel,Garcia, M. Teresa,Gathergood, Nicholas
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body text
p. 1350 - 1356
(2012/06/16)
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- A [3+3] cyclization strategy for asymmetric synthesis of alkyl substituted piperidine-2-ones using 1,2-cyclic sulfamidates: A formal synthesis of (S)-coniine from l-norvaline
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Regioselective ring-opening reactions of a set of representative 1,2-cyclic sulfamidates with lithium triethylorthopropiolate proceeded efficiently to deliver the corresponding δ-amino-α,β-unsaturated esters after acidic hydrolysis. Hydrogenation of the unsaturated esters and subsequent thermal cyclization afforded the related alkyl substituted piperidine-2-ones. This approach represents a novel [3+3] cyclization strategy for the asymmetric synthesis of alkyl substituted piperidin-2-ones. Efficiency of the cyclization process is illustrated by a formal asymmetric synthesis of (S)-coniine from l-norvaline.
- Karanfil, Abdullah,Balta, Berrin,Eskici, Mustafa
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p. 10218 - 10229,12
(2020/09/02)
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- Hydantoin-free synthesis of peptide ester isocyanates, isothiocyanates, and dipeptidyl ureas: The application of zinc dust in a carbonylation procedure without base
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Non-Schotten-Baumann conditions are described for the hydantoin-free synthesis of peptide ester isocyanates using activated zinc dust as a non-basic HCl scavenger. Also, the procedure gives no N-acylated products in the case of the conversion of amino acid and peptide amides into isocyanates. Georg Thieme Verlag Stuttgart · New York.
- Narendra,Vishwanatha,Sureshbabu, Vommina V.
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body text
p. 3247 - 3254
(2011/11/30)
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- Chiral 1,5-disubstituted 1,3,5-hexahydrotriazine-2-N-nitroimine analogues as novel potent neonicotinoids: Synthesis, insecticidal evaluation and molecular docking studies
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A new series of 1,5-disubstituted 1,3,5-hexahydrotriazine-2-N-nitroimines (4a-4x) were designed and synthesized as novel chiral neonicotinoid analogues. The single-crystal structure of 4n was further determined by X-ray diffraction, and its S configuration was confirmed. Preliminary bioassay showed that compound 4e, 4k, 4u, 4v exhibited excellent insecticidal activities at 100 mg/L, while 4k had >90% mortality at 10 mg/L, which suggested it could be used as a lead for future development. Modeling the inhibitor-nAChR complexes by molecular docking studies explained the structure-activity relationships observed in vitro, and revealed an intriguing molecular binding mode at the active site of nAChR, which raised the possibility that these analogues may arbitrate their insecticidal activity through a mechanism other than imidacloprid.
- Sun, Chuanwen,Zhu, Jun,Wang, Haifeng,Jin, Jia,Xing, Jiahua,Yang, Dingrong
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experimental part
p. 11 - 20
(2011/02/27)
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- Effect of substituents on enantioselectivity in chiral oxazaborolidine mediated asymmetric ketone reduction reaction
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Various new chiral ligands have been synthesized by the condensation of different esters of L-Valine with different substituted salicylaldehydes in order to find the most effective catalyst for the enantioselctive ketone reduction. Chiral amine synthesized from L-Valine methyl ester and 5-chloro salicylaldehyde is found to catalyse the enantioselective reduction of prochiral ketone with high yield (99%) and enantiomeric excess (91%) with 20 mol% of the catalyst using borane dimethylsulphide as a stoichiometric reducutant. Different subsituted prochiral ketones have also been reduced in high yield upto 90% and the corresponding secondary alcohols are formed with good enantiomeric excess upto 99%. The mechanism of this reduction can be very well explained by considering a plausible mechanism for the CBS catalyst.
- Balakrishnan,Ananthi,Velmathi
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experimental part
p. 1157 - 1164
(2011/10/13)
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- Anthranilic acid based CCK1 receptor antagonists: Blocking the receptor with the same 'words' of the endogenous ligand
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The anthranilic acid diamides represent the more recent class of nonpeptide CCK1 receptor antagonists. This class is characterized by the presence of anthranilic acid, used as a molecular scaffold, and two pharmacophores selected from the C-terminal tetrapeptide of CCK. The lead compound coded VL-0395, endowed with sub-micromolar affinity towards CCK1 receptors, was characterized by the presence of Phe and 2-indole moiety at the C- and N-termini of anthranilic acid, respectively. Herein we describe the first step of the anthranilic acid C-terminal optimization using, instead of Phe, aminoacids belonging to the primary structure of CCK-8 and other not coded residues. Thus we demonstrate that the CCK1 receptor affinity depends on the nature of the aminoacidic side chain as well as that the free carboxy group of the alpha-aminoacids is crucial for the binding. The R enantiomers of the most active compounds represent the eutomers of this class of antagonists confirming thus the stereo preference of the receptor. Moreover this SAR study demonstrates that the receptor binding pocket, that host the aminoacidic side chain, results much more tolerant respect to that accommodating the indole ring. As a result, an appropriate variation of the aminoacidic side chain could provide a better CCK1 receptor affinity diorthosis.
- Lassiani, Lucia,Pavan, Michela V.,Berti, Federico,Kokotos, George,Markidis, Theodoros,Mennuni, Laura,Makovec, Francesco,Varnavas, Antonio
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experimental part
p. 2336 - 2350
(2009/09/05)
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- Diastereoselective Ugi reaction without chiral amines: the synthesis of chiral pyrroloketopiperazines
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The three-component Ugi reaction with chiral 2-(2-formyl-1H-pyrrol-1-yl)acetic acids prepared from natural l-aminoacids was investigated. The reaction opens a new route to chiral substituted pyrroloketopiperazines. One of the first examples of an asymmetric Ugi reaction without chiral amines is described. The reaction proceeds with moderate diastereoselectivity to give the target compounds in good yields. The scope and limitation of the approach are discussed.
- Nenajdenko, Valentine G.,Reznichenko, Alexander L.,Balenkova, Elizabeth S.
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p. 3031 - 3041
(2007/10/03)
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- Organosilicon synthesis of isocyanates: IV. Synthesis of isocyanates from aliphatic and alkylaromatic amino acid esters
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Treatment of an alcoholic suspension of amino acids with trimethylchlorosilane yielded phenylglycine, valine, β-phenylalanine, and homovaline ester hydrochlorides. Their saccharin-catalyzed silylation with hexamethyldisilazane proceeds quantitatively and involves only one proton of the amino group. The best conversion of the amino acid esters to the corresponding isocyanates was achieved by phosgene treatment of their monosilyl urethanes, rather than of the silylated amino esters. Monosilyl urethanes are formed quantitatively by treatment of the amino acid ester hydrochlorides with the hexamethyldisilazane-CO2 system. The 1H NMR spectra show that monosilyl urethanes derived from α-and β-amino acid esters are characterized by intramolecular interaction of the silicon atom and the oxygen atom of the carboxy group. Nauka/Interperiodica 2007.
- Lebedev,Lebedeva,Sheludyakov,Shatunov,Ovcharuk
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p. 581 - 585
(2008/02/11)
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- Electrophilic amination of enolates with oxaziridines: Effects of oxaziridine structure and reaction conditions
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A range of N-alkoxycarbonyl- and N-carboxamido-oxaziridines has been prepared to test the effects of oxaziridine structure on yields of enolate amination product. Side-products arising from reaction of aldehyde-derived oxaziridines with base were identified, while a ketone-derived oxaziridine afforded moderate yields of amination product with stabilised carbanions.
- Armstrong, Alan,Edmonds, Ian D.,Swarbrick, Martin E.,Treweeke, Nigel R.
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p. 8423 - 8442
(2007/10/03)
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- Stereocontrolled synthesis of β-lactams via staudinger reaction between phenoxyketenes and chiral imines
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Chiral Schiff bases derived from esters of valine and alanine have been shown to be useful intermediates for the stereoselective synthesis of β-lactams. Staudinger reaction between these compounds and phenoxyketenes, generated in situ, from the corresponding acid chlorides in the presence of triethylamine, provides a mixture of diastereomeric cis-β-lactams. Attempts have been made to separate them using column chromatography and their ratios determined through 1H NMR data.
- Kanwar, Seema,Saluja, Aarti,Khurana,Sharma
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p. 137 - 141
(2007/10/03)
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- 9. Les β-cetonitriles groupes protecteurs de la fonction amine. Preparation d'amino-alcools
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β-Ketonitrile-Derived Protecting Groups of the Amino Function.Synthesis of Amino Alcohols.The amino group of natural L-amino acid esters is protected by condensation with 2-oxocyclopentanenitrile (1) or 2-formyl-2-phenylacetonitrile (10).Only the ester group of the formed cyanoenamino esters 2 and 11 reacts with nucleophilic reagents such as organometallics (RMgX, RLi), borohydrides, or metal amides, whereas the cyanoenamino group is unchanged (Schemes 1 and 2).Cyanoenamino alcohols obtained by reduction of cyanoenamino esters 2 are hydrolyzed under acidic conditions to amino alcohols with retention of the configuration of the starting amino acid.This sequence of reactions allows to prepare derivatives of L-tyrosinol from (-)-L-tyrosine (see, e.g., Scheme 4).Cyanoenamino esters 11 are readily methylated at the N-atom to give N-methylated cyanoenamino esters (Scheme 3).This property is exploited on the way of multistep procedure to obtain N-methylated amino alcohols homologous to natural (-)-(1R,2S)-ephedrine.
- Abarbri, Mohamed,Guignard, Alain,Lamant, Maurice
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p. 109 - 121
(2007/10/02)
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- TRANSFORMATION OF GLYCYRRHIZIC ACID. VII. SYNTHESIS OF TRITERPENE GLYCOPEPTIDES CONTAINING ALKYL ESTERS OF L-AMINO ACIDS
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The synthesis has been effected by the activated N-hydroxy succinimide ester method of new triterpene glycopeptides derived from glycyrrhizic acid, containing fragments of alkyl (ethyl, propyl, butyl) esters of L-amino acids.
- Baltina, L.A.,Ryzhova, S.A.,Vasil'eva, E.V.,Tolstikov, G.A.
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p. 238 - 244
(2007/10/02)
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- KINETICS OF THE ALKALINE HYDROLYSIS OF SEVERAL N-BENZYLOXYCARBONYLDIPEPTIDE METHYL AND ETHYL ESTERS
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The reaction rates of the alkaline hydrolysis of synthesized N-protected dipeptide methyl and ethyl esters were studied systematically.From the kinetic data the energies of activation, the pre-exponential factors and the reference values at 40 deg C were calculated.The rate of hydrolysis shows to be strongly dependent on the C-terminal amino acid in the sequence Gly >> Ala/Met/Phe > Leu >> Val/Pro.Surprisingly the N-terminal amino acid also exerts an effect, but in a different sequence.N-Terminal Phe in particular shows a relative accelerating effect.Remarkable is the significantly faster ester hydrolysis of glycine containing dipeptide ethyl esters in ethanol/water compared to the corresponding methyl esters in methanol/water.
- Hoogwater, D. A.,Peereboom, M.
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p. 5325 - 5332
(2007/10/02)
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- Synthesis of "Chiral" α-Aminoisobutyric Acid
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α-Methylalanine (α-aminoisobutyric acid), a rare naturally occuring achiral amino acid, is an efficient inducer of secondary structure for peptides and easy to characterize by NMR because of its prochiral methyl groups. "Chiral" α-methylalanine is enantioselectively synthesized via the bislactim-ether method where the pro-R-methyl group has three or one deuterium atom(s).
- Weihrauch, Thomas,Leibfritz, Dieter
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p. 1917 - 1921
(2007/10/02)
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